You are on page 1of 84

Special Considerations in the Management of HIV-Infected Women, Including

Management of Conception and Pregnancy

Author: Kristine Patterson, MD (More Info)

Section Editor: Judith S. Currier, MD, MSc

Editors in Chief: Joseph J. Eron, Jr., MD; Daniel R. Kuritzkes, MD; Kathleen E. Squires, MD

Last Reviewed: 4/24/14 (What's New)

Introduction

SUMMARY

Approximately 25% of HIV/AIDS cases in the United States today are among women, one third of
whom are 50 years of age or older

[CDC 2013a; CDC 2013b]

Most HIV infections in US women occur through heterosexual intercourse

HIV-infected women tend to have higher rates of antiretroviral interruption than men

Sex-specific issues such as pregnancy and menopause have become a more important part of HIV
care as life expectancy of HIV-infected women has improved

Approximately 25% of all HIV/AIDS cases in the United States today are among women,
2013b]

which is an increase from 7% in 1985.

50 years of age or older.

[CDC 2012; CDC 2013b]

[ACOG 2010]

[CDC 2013a; CDC

Furthermore, approximately 30% of women with HIV are

The predominant mode of HIV transmission among women

continues to be through heterosexual intercourse.

[CDC 2013a]

Recent data suggest that although women tend to

have more favorable clinical parameters at primary infection diagnosis when compared with men, subsequently
women tend to have poorer clinical outcomes than men. This has been most prominent in nonwhite women
and in women from the southern United States, who progress more rapidly than other groups.

[Meditz 2011]

HIV-

infected women face the same social stressors and life-altering events that all other women face. However,
these events are further complicated by an underlying chronic medical illness that, without proper medical
treatment, is fatal. With the widespread use of potent combination antiretroviral therapy, women are now living
longer with HIV. As a result, many HIV-infected women will undergo normal life events, including pregnancy
and menopause. Although women of childbearing potential continue to encompass the majority of women
living with HIV, the number of older HIV-infected women increases each year. Tremendous progress has been
made in addressing female-specific issues surrounding HIV care. Despite these efforts, however, many
unanswered questions remain, and the HIV research and healthcare community must continue to strive to
address sex-specific care-related questions so that management of HIV-infected women continues to improve.
This module focuses on specific topics to consider in the clinical care of HIV-infected women in different life
stages. In addition, a global overview of treatment-related issues and complications specific to HIV-infected
women will be provided. For a more comprehensive overview of specific issues related to the clinical care of

HIV-infected women, please refer to the 2013 US Department of Health and Human Services
guidelines (Management Guidelines).

[DHHS Women]

For additional information from inPractice on the epidemiology in the developed world, click here.

Keywords: Special Populations, Women

Special Considerations in the Management of HIV-Infected Women, Including


Management of Conception and Pregnancy

Author: Kristine Patterson, MD (More Info)

Section Editor: Judith S. Currier, MD, MSc

Editors in Chief: Joseph J. Eron, Jr., MD; Daniel R. Kuritzkes, MD; Kathleen E. Squires, MD

Last Reviewed: 4/24/14 (What's New)

Primary Care of HIV-Infected Women


SUMMARY

Standard female-focused primary care should be incorporated into routine care of HIV-infected
women

Immunizations

The following vaccinations are recommended in HIV-infected individuals (Management


Guidelines)

[CDC OI]

(Management Guidelines)

[ACIP Schedule]

Hepatitis A adult vaccine for individuals without detectable immunity and at risk for
acquiring hepatitis A

Hepatitis B adult vaccine for individuals without indication of past or present


infection

Pneumococcal 13-valent conjugate vaccine and pneumococcal 23-polyvalent


vaccine

Tetanus/diphth/pertuss (Tdap) adult/adol

Meningococcal conjugate vaccine for individuals at risk for acquiring meningococcal


disease

Measles/mumps/rubella virus vaccine is recommended in HIV-infected persons 12 months of


age or older who do not have severe immunosuppression

Varicella virus vaccine, and zoster vaccine live may be appropriate for some individuals, but
are contraindicated for patients with CD4+ cell counts < 200 cells/mm

Primary care guidelines from HIVMA/IDSA recommend HPV vaccination for all females 9-26
years of age (Management Guidelines)

3[CDC OI; Harpaz 2008]

[Aberg 2014]

Anthrax vaccine adsorbed and smallpox vaccine should be avoided for all HIV-infected
women

Screening and Risk Factor Assessment

Guidelines on opportunistic infections recommend testing for latent TB infection at HIV


diagnosis and annually thereafter in HIV-infected women with an ongoing risk for acquiring
TB (Management Guidelines)

[CDC OI]
3

Testing may be repeated in patients whose CD4+ cell count was < 200 cells/mm at initial
3

[CDC OI]

screening but is 200 cells/mm on ART

WHO guidelines recommend that HIV-infected patients in resource-constrained settings


should be screened for TB at each clinical interaction (Management Guidelines)

[WHO HIV]

HIV-infected patients should be screened for cardiovascular disease risk factors at each
physician visit and behavioral and pharmacological interventions initiated as appropriate

[Currier

2008]

Primary care guidelines from HIVMA/IDSA recommend annual mammography for women
aged 50 years or older, and performing individualized assessment of risk for breast cancer
followed by discussion of the risks and benefits screening mammography with women
between 40 and 49 years of age (Management Guidelines)

[Aberg 2014]

Because of the successes in identifying and treating HIV, women are now living longer with HIV infection and
are initiated on combination antiretroviral therapy at higher CD4+ cell counts. As a result, standard femalefocused primary care must be incorporated into the routine care of HIV-infected women. Clinicians must
consider that many medical complaints made by HIV-infected women are not HIV related.

Immunizations
Routine clinical care should include immunizations, and vaccine recommendations are similar between HIVpositive and HIV-negative patients. However, HIV can change the efficacy and/or safety of vaccines, and the
benefits of vaccination should be weighed against the risks to the patient.

[Parmigiani 2013]

For example, preliminary

data regarding the human papillomavirus vaccine indicate that this vaccine is both safe and immunogenic in
HIV-positive young women.

[Kojic 2011a; Firnhaber 2012; Kahn 2013; Sow 2013]

However, the varicella virus vaccine and zoster


3 [CDC OI; Harpaz 2008]

vaccine live are contraindicated for patients with CD4+ cell counts < 200 cells/mm .

The following vaccinations are recommended (Management Guidelines)


Centers for Disease Control and Prevention (Management Guidelines)

[CDC OI]

and have been outlined by the

[ACIP Schedule]

Hepatitis A adult vaccine (2 doses within 1-1.5 years) for individuals without detectable immunity and at risk for
acquiring hepatitis A (eg, from injection drug use, chronic hepatitis B or C infection, other chronic liver
diseases, or a bisexual partner)

Hepatitis B adult vaccine (3 doses within 6 months) for individuals without indication of past or present infection

Pneumococcal 13-valent conjugate vaccine (1 dose) and pneumococcal 23-polyvalent vaccine (1


dose administered 8 weeks afterpneumococcal 13 valent conjugate vaccine in patients with CD4+ cell count
3

200 cells/mm or after CD4+ cell count reaches 200 cells/mm in patients with CD4+ cell count < 200
3

cells/mm ), with pneumococcal 23-polyvalent vaccine booster every 5 years, not to exceed 3 lifetime
doses (Management Guidelines)

[CDC OI]

Influenza virus vaccine, inactivated every fall for women who are not allergic to eggs; the nasal spray influenza
virus vaccine, live should not be administered

Tetanus/diphth/pertuss (Tdap) adult/adol (1 dose) with tetanus toxoid and diphtheria booster (Td) every 10
years; if pregnant, administer Td during second or third trimester or defer until after pregnancy and administer
TdaP

Meningococcal conjugate vaccine (1 or more doses) for individuals at risk for acquiring meningococcal disease
(eg, college students, military recruits, people traveling to endemic areas)

Measles/mumps/rubella virus vaccine (2 doses) is recommended in HIV-infected persons 12 months of age or


older who do not have severe immunosuppression; persons with perinatal HIV infection who were vaccinated
with measles/mumps/rubella virus vaccineprior to initiating antiretroviral therapy should be revaccinated (2
appropriately spaced doses) after establishing an effective antiretroviral therapy regimen

[McLean 2013]

Human papillomavirus vaccine (either bivalent or quadrivalent; 3 doses within 6 months) for women 9-26 years
of age; not recommended during pregnancy

Varicella virus vaccine (2 doses) is recommended for individuals with CD4+ cell count 200 cells/mm and
without a history of chicken pox or evidence of immunity serologically but is contraindicated for individuals with
3

CD4+ cell count < 200 cells/mm and is not recommended during pregnancy

Zoster vaccine live (1 dose) is not routinely recommended but may be given to individuals older than 50 years
3

of age with CD4+ cell count 200 cells/mm and evidence of varicella immunity; a randomized phase II trial in
3

HIV-infected patients on stable antiretroviral therapy with CD4+ cell counts 200 cells/mm demonstrated the
safety and immunogenicity of this vaccine in the indicated patient population (Capsule Summary)

[Benson 2012]

The anthrax vaccine adsorbed and the smallpox vaccine should be avoided for all HIV-infected women.

For additional information from inPractice on immunizations for HIV-infected patients, click here.

For additional information from inPractice on hepatitis virus coinfection, click here.

For additional information from inPractice on other viral infections, click here.

For additional information from inPractice on bacterial infections, click here.

Screening and Risk Factor Assessment


The 2013 Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and
Adolescents recommend testing for latent tuberculosis infection at the time of HIV diagnosis and annually
thereafter in HIV-infected women with an ongoing risk for acquisition of tuberculosis (Management
Guidelines).

[CDC OI]

Testing may be repeated in HIV-infected patients who had a baseline CD4+ cell count < 200

cells/mm after they achieved a CD4+ cell count 200 cells/mm on antiretroviral therapy.

[CDC OI]

The World

Health Organization clinical guidelines recommend that HIV-infected patients in resource-constrained settings
should be screened for tuberculosis at each clinical interaction by assessing potential symptoms of infection
(coughing, fever, weight loss, and night sweats) and performing diagnostic tests if symptoms are
present (Management Guidelines).

[WHO HIV]

Although traditional screening methods include a tuberculin skin test, screening with newer tests such as
interferon gamma release assays may provide advantages in HIV-infected patients, because results are
obtained immediately and may be more accurate than traditional skin tests; however, these methods are still
controversial.

[Kunimoto 2006; Jones 2007; Sauzullo 2010; Redelman-Sidi 2013;Kowada 2014]

Patients who were screened initially with a

CD4+ cell count < 200 cells/mm should be rescreened after immune reconstitution. In individuals with a
previous history of a positive tuberculin skin test, a symptom-focused questionnaire should be performed.
Annual chest radiographs for tuberculosis in the absence of symptoms is not indicated.

For additional information from inPractice on tuberculosis screening in HIV-infected patients, click here.

HIV infection may increase the risk of cardiovascular disease, particularly in patients with other modifiable risk
factors; therefore, screening HIV-infected patients for cardiovascular disease risk factors is important.
2007; Freiberg 2013]

[Kaplan

Traditional modifiable risk factors for cardiovascular disease include cigarette smoking,

hypertension, hyperlipidemia, diabetes, and obesity. The most recent guidelines for managing blood
cholesterol identify 4 risk groups of patients for whom moderate- to high-intensity statin therapy is
recommended and advise clinicians to use risk assessment tools to inform statin therapy decisions rather than
target lipoprotein values (Management Guidelines).

[ACC/AHA Cholesterol]

Risk factors should be addressed at each

physician visit and behavioral and pharmacological interventions initiated as appropriate.

[Currier 2008]

Commonly

used algorithms to predict risk of cardiovascular disease are broadly accurate in HIV-infected populations,

although the Framingham, SCORE, and D:A:D algorithms all underestimate the presence of subclinical
[Serrano-Villar 2012; Chew 2013]

atherosclerosis and coronary heart disease in HIV-infected patients.

For additional information from inPractice on cardiovascular risk in HIV-infected patients, click here.

The American Cancer Society recommends mammograms and self-breast examinations for women,
regardless of HIV status, beginning at the age of 40 years (Management Guidelines).

[ACS 2003]

A guideline panel

expanded on and developed new recommendations for women at different defined levels of risk. This new
guideline states that screening magnetic resonance imaging is recommended for women with an
approximately 20% to 25% or greater lifetime risk of breast cancer, including women with a strong family
history of breast or ovarian cancer and women who were treated for Hodgkins disease.

[Saslow 2007]

The exact

age at which to start mammograms is controversial. Primary care guidelines from the HIV Medical Association
of the Infectious Diseases Society of America recommend an annual mammography for women aged 50 years
or older, and performing individualized assessment of risk for breast cancer followed by discussion of the risks
and benefits screening mammography with women between 40 and 49 years of age (Management
Guidelines).

[Aberg 2014]

There are no data to suggest that HIV-infected women are at a higher risk for developing

breast cancer compared with HIV-negative women.

[Grulich 2007]

For additional information from inPractice on breast cancer in HIV-infected women, click here.

Psychosocial stressors should be evaluated on a regular basis in HIV-infected women. A multidisciplinary team
that incorporates social services, mental health, and case management is often required to maintain ongoing
clinical care and medication compliance in this population.

[Cunningham 2008; Pillai 2009]

This module includes specific guidance regarding cervical cancer screening and assessment of depression.

Special Considerations in the Management of HIV-Infected Women, Including


Management of Conception and Pregnancy

Author: Kristine Patterson, MD (More Info)

Section Editor: Judith S. Currier, MD, MSc

Editors in Chief: Joseph J. Eron, Jr., MD; Daniel R. Kuritzkes, MD; Kathleen E. Squires, MD

Last Reviewed: 4/24/14 (What's New)

Overview of Health Considerations:


Reproductive Health
SUMMARY

Contraception options offered to the general population may not be available or appropriate for
women who are HIV positive

Oral Contraceptives

Data on whether the use of hormonal contraceptives effect the progression of HIV disease
are conflicting

[Cejtin 2003; Kilmarx 2000; Richardson 2007; Heffron 2013; Stringer 2009; Phillips 2013]

WHO recommends that women infected with HIV use hormonal contraceptives to prevent
[WHO 2012]

pregnancy

Co-administration of antiretroviral agents may alter the clinical effectiveness of some oral
contraceptives and the pharmacokinetics and efficacy of some antiretrovirals (Table 1)

[Ouellet

1998; Mildvan 2002; Chu 2005; Anderson 2011; El-Ibiary 2008; Crauwels 2009; DHHS Perinatal; Robinson 2012; Tseng 2013; Landolt
2013; ELV/COBI/TDF/FTC PI; Song 2013]

Hormonal contraceptives should be used in conjunction with barrier contraceptives


(condoms)

Injectable Contraceptives

Clinically important pharmacokinetic interactions between progestin injectable contraceptives


and antiretrovirals have not been reported, although data on ritonavir- or cobicistat-boosted
agents are lacking

[Cohn 2007; Nanda 2008; Watts 2008]

DMPA may be associated with an elevated HIV-1 RNA set point when used at the time of
HIV acquisition

[Lavreys 2004]

Data suggesting an association between DMPA use and HIV acquisition or transmission are
controversial, and additional studies are needed

[Noguchi 2014; Polis 2013a; Polis 2013b; Polis 2013c; Lutalo

2013; Heffron 2012; Morrison 2012; McCoy 2013]

Patients and their partners should be counseled regarding continued use of barrier
contraception (condoms) in addition to other contraceptive choices

Implantable, Intravaginal, and Intrauterine Contraceptives

All combined hormonal contraceptive methods are listed as Category 1 (no restriction for
use) for women at high risk for HIV or with HIV or AIDS by the CDC Medical Eligibility
Criteria for Contraceptive Use

[CDC MEC]

Efavirenz may decrease etonogestrel levels attained from the etonogestrel implant

[DHHS

Perinatal; Leticee 2012]

The TCu-380A IUD and the levonorgestrel-releasing intrauterine contraceptive system are
acceptable choices for HIV-infected women at low risk for acquiring STDs

[DHHS ART]

Barrier Contraceptives

Barrier methods, such as condoms, should be encouraged in all HIV-infected individuals


even when other forms of contraception are used

Spermicides containing nonoxynol 9 topical should not be used for prevention of HIV or
STDs

[WHO 2001]

There are special considerations for reproductive health in HIV-infected women when compared with the
general population. Issues surrounding contraception are multifaceted for HIV-infected women. These women
often feel stigmatized by their diagnosis and, therefore, do not seek appropriate care. Furthermore,
contraception options available to the general population may not be available or appropriate for HIV-positive
women, and there is minimal evidence-based guidance to direct practitioners in this arena.

Oral Contraceptives
The studies that have evaluated whether the use of hormonal contraceptives has any effect on chronic HIV
infection have demonstrated conflicting results. Some studies have not observed an association between
hormonal contraception and HIV disease progression.

[Cejtin 2003; Kilmarx 2000; Richardson 2007; Heffron 2013]

In a study of

Zambian women not yet receiving antiretroviral therapy, the use of depomedroxyprogesterone acetate or oral
contraceptives was associated with an accelerated HIV disease progression and death.

[Stringer 2009]

A systematic

review of randomized clinical trials and cohort studies found no evidence that hormonal contraceptives

increase a womans risk of HIV disease progression.

[Phillips 2013]

Therefore, hormonal contraceptive choices

should be based on each womans needs rather than possible effects on HIV progression.
2013]

[Gollub 2012; Phillips

The World Health Organization recommends that women infected with HIV or at high risk of HIV can

continue to use hormonal contraceptives to prevent pregnancy.

[WHO 2012]

The primary concern in HIV-infected women should be focused on effects the antiretroviral agents may have
on the clinical effectiveness of available contraceptive choices (Table 1). Therefore, any nonbarrier
contraceptive should be used in conjunction with a barrier (condom) device, not only for pregnancy prevention
but also to prevent HIV transmission. In addition, contraceptive agents may alter the pharmacokinetics and
efficacy of certain antiretrovirals. Virologic responses to antiretroviral therapy should be monitored closely
when used in combination with nonbarrier contraceptives. Pharmacokinetic interaction should be considered
when combined oral contraceptives and antiretrovirals are used together and certain agents should not be
used concurrently (Table 1).

[Ouellet 1998; Mildvan 2002; Chu 2005;Anderson 2011; El-Ibiary 2008; Crauwels 2009; DHHS Perinatal; Robinson

2012; Tseng 2013; Atrio 2014; Thurman 2014]

Specifically, recent data have demonstrated a negative effect on both

progesterone and antiretroviral levels when efavirenz and combined oral contraceptives are
coadministered.

[Landolt 2013]

Elvitegravir/cobicistat increased norgestimate exposures, which may potentially

increase the risk of complications including insulin resistance, dyslipidemia, acne, and venous
thrombosis.

[ELV/COBI/TDF/FTC PI]

The potential risks and benefits of using norgestimate-containing contraceptives in

combination with cobicistat and elvitegravir should be considered, particularly in women who have risk factors
for these complications.

Table 1. Effects of Coadministration of Antiretroviral Therapy and


Combined Oral Contraceptives
Antiretroviral Agent
NRTIs
NNRTIs

Efavirenz

Etravirine

Nevirapine

Rilpivirine
PIs

Overall Effect or
Recommendation
No effect
Progestin levels markedly decreased
Effectiveness of emergency
contraception may be diminished
Barrier method should be used
No dose adjustment needed
Additional methods recommended;
alternative methods can be considered
No dose adjustment needed
No dose adjustment

Atazanavir

Atazanavir/ritonavir

Darunavir/ritonavir

Fosamprenavir

Fosamprenavir/ritonavir

Indinavir

Lopinavir/ritonavir

Nelfinavir

Ritonavir

Saquinavir/ritonavir

Tipranavir/ritonavir

Integrase Inhibitors
Raltegravir

Cobicistat/elvitegravir/emtricitabine/tenofovir

Dolutegravir

CCR5 Antagonist
Maraviroc

Use with caution; COC should contain


no more than 30 g of ethinyl estradiol
Additional or alternative method
recommended
Additional or alternative method
recommended
Reduced amprenavir levels when
fosamprenavir coadministered with
ethinyl estradiol/norethindrone; may
lead to loss of virologic response
Use alternative contraceptive method
Additional or alternative method
recommended
No dose adjustment
Additional or alternative method
recommended
Additional or alternative method
recommended
Use alternative contraceptive method
Additional or alternative method
recommended
Additional or alternative method
recommended
No dose adjustment needed
Ethinyl estradiol levels decreased
Progestin levels increased
No dose adjustment needed
No dose adjustment needed[Song 2013]

No dose adjustment needed

COC, combined oral contraceptives; DMPA, depot medroxyprogesterone acetate.

For additional information from inPractice on drugdrug interactions between antiretroviral agents and
hormonal contraceptives, click here.

Injectable Contraceptives

There are no clinically important pharmacokinetic interactions that occur when progestin injectable
contraceptives, such as depot-medroxyprogesterone acetate (DMPA), are used with antiretrovirals; however,
formal studies examining the potential for interaction withritonavir-boosted PIs or cobicistatboosted elvitegravir have not been conducted.

[Cohn 2007; Nanda 2008; Watts 2008]

elevated HIV-1 RNA set point when used at the time of HIV acquisition,

DMPA may be associated with an

[Lavreys 2004]

and this could result in more

rapid disease progression. HIV-infected and HIV-uninfected women experience similar adverse effects when
using injectable hormonal contraceptives.

Whether DMPA use is associated with HIV acquisition or transmission is controversial and additional studies
are needed to provide clarity.
prospective cohort,

[Heffron 2012]

[Polis 2013a]

Currently available data include a retrospective analysis from a


[Polis 2013b]

a systematic review

the VOICE trial (Capsule Summary)

[Noguchi 2014]

and a preplanned secondary analysis of data from

suggesting that there may be an increased risk of HIV

acquisition and/or transmission with the use of hormonal contraceptive pills and/or DMPA. However, these
analyses each have limitations and do not provide irrefutable evidence that contraception and HIV
transmission or acquisition are linked. Other publications do not find an association between injectable
contraceptive use and HIV acquisition or transmission.

[Morrison 2012;McCoy 2013; Polis 2013c; Lutalo 2013]

Following the initial

publication demonstrating an increased risk of HIV acquisition with DMPA, the World Health Organization
issued a statement indicating that it did not find the evidence compelling enough to warrant changing the
current recommendations regarding hormonal contraceptive use.

[WHO 2012]

Patients and their partners should be

counseled regarding the continued use of barrier contraception (condoms) in addition to other contraceptive
choices.

Implantable, Intravaginal, and Intrauterine Contraceptives


Limited data exist regarding the use of implantable or intravaginal contraception in HIV-infected women.
However, the Centers for Disease Control and Preventions Medical Eligibility Criteria for Contraceptive Use
lists all combined hormonal contraceptive methods (including the patch and vaginal ring) as Category 1 (no
restriction for use) for women at high risk for HIV or with HIV or AIDS.

[CDC MEC]

There is some indication that

use of efavirenz may decrease etonogestrel levels attained from the etonogestrel implant.

[DHHS Perinatal; Leticee 2012]

Both the copper-containing intrauterine device (TCu-380A IUD) and the levonorgestrel-releasing intrauterine
contraceptive system are acceptable choices for HIV-infected women at low risk for acquiring sexually
transmitted diseases.

[DHHS ART]

Barrier Contraceptives
Barrier methods, such as condoms, should be encouraged in all HIV-infected individuals even when other
forms of contraception are used. Condoms must be used consistently and correctly for effective contraception,
for the prevention of sexually transmitted infections, and for the prevention of HIV transmission. Spermicides
containing nonoxynol 9 topical should not be used for the prevention of HIV or sexually transmitted infection
transmission; products containing nonoxynol 9 topical may increase the risk of HIV transmission.

[WHO 2001]

Sexually Transmitted Diseases in HIVInfected Women


SUMMARY

STDs can facilitate HIV transmission by increasing genital shedding of HIV

Sexually active women should receive routine screening for STDs, with increased frequency in the

[Cohen 1997]

following situations:

With a new HIV diagnosis

At each annual examination

With a new sexual partner

Following a condom malfunction

After unprotected intercourse

When there is a known exposure to an STD

STD screening should include tests for gonorrhea, chlamydia, trichomonas, syphilis, bacterial
vaginosis, vulvovaginal candidiasis, HSV, and HPV

Women who test positive for gonorrhea, chlamydia, trichomonas, or syphilis should be counseled
regarding safe sexual practices and use of barrier contraception

Gonorrhea, chlamydia, chancroid, and syphilis are reportable STDs in the United States; additional
reporting requirements vary by state

[CDC STD 2010]

Unprotected sexual intercourse is the most common mode for transmission of HIV and other sexually
transmitted diseases (STDs).

[Cohen 1998]

The presence of an STD in HIV-infected individuals can facilitate HIV

transmission by increasing genital shedding of HIV.

[Cohen 1997; Fastring 2014]

STDs are an important part of an HIV prevention strategy.

Therefore, detection and treatment of

Women should be counseled routinely to use barrier contraceptive methods to prevent acquisition of an STD,
even if other contraceptive methods are already in use. Routine screening for STDs should occur in sexually
active women and should be performed more often in the following situations:

With a new HIV diagnosis

At each annual examination

With a new sexual partner

Following a condom malfunction

After unprotected intercourse

When there is a known exposure to an STD

Women should be evaluated for the following STDs:

Gonorrhea/chlamydia

Screen annually in sexually active women or woman with recent change in sexual partner or sexual practice, if
partner has a history of STDs, or if the woman presents with signs or symptoms

Trichomonas vaginalis

Syphilis

Should be screened for annually and if neurologic symptoms occur

Herpes simplex virus

Bacterial vaginosis

Although not an STD, bacterial vaginosis increases HIV infectiousness

Vulvovaginal candidiasis

Recurrent episodes may be an indication of HIV disease progression

Human papillomavirus

Refer to cervical cancer screening

[Atashili 2008]

Women who test positive for gonorrhea, chlamydia, trichomonas, or syphilis should be counseled regarding
safe sexual practices and the use of barrier contraception. Gonorrhea, chlamydia, chancroid, and syphilis are
reportable STDs according to the Centers for Disease Control and Prevention Guidelines (Management
Guidelines).

[CDC STD 2010]

The guidelines for reporting of specific STDs vary by state.

Cervical Cancer Screening in HIV-Infected


Women
SUMMARY

Incidence of CIN is 4-5 times higher in women infected with HIV than in HIV-negative women

[Wright

1994a; Wright 1994b; Ellerbrock 2000]

Use of ART is associated with regression of cervical dysplasia

In resource-limited countries, cervical cancer screening follows the screen-and-treat model, with
cryosurgery performed at the same visit for women with abnormal findings (Management
Guidelines)

[USNCI Cervical]

In developed countries, women should undergo cervical cancer screening, including HPV testing and
a Pap test, every 6 months in the first year after HIV diagnosis and annually thereafter (Management
Guidelines)

[CDC OI]

Cervical cancer screening should be performed annually regardless of age in women who acquired
HIV infection through sexual intercourse

[CDC OI]

Colposcopy should be offered based on cervical cytology results and HPV DNA (Table 2)

[Cohn

2001; Goldie 2001; Harris 2005;Kitchener 2007]

Guidelines on opportunistic infections suggest anal cytologic screening for HIV-infected women,
followed by high-resolution anoscopy in women with abnormal cytologic results

[CDC OI]

Primary care guidelines from HIVMA/IDSA recommend HPV vaccination for all females 9-26 years of
age (Management Guidelines)

[Aberg 2014]

Screening for cervical cancer is important for all HIV-infected women regardless of reproductive status. The
incidence of cervical intraepithelial neoplasia (CIN) among HIV-infected women is 4-5 times higher than in HIVnegative women and is inversely correlated with CD4+ cell counts.
2013]

[Wright 1994a; Wright 1994b; Ellerbrock 2000; Abraham

The risk of human papillomavirus (HPV) infection with the high-risk HPV subtypes (16 and 18) and the

development of high-grade CIN increase with increasing immunosuppression.

[Hawes 2003;Volkov 2001; Denslow 2014]

The

use of antiretroviral therapy, however, is associated with regression of cervical dysplasia, which has not been
reported in the absence of antiretroviral therapy.

[Heard 2002]

In resource-limited countries, the rate of cervical cancer is higher than in developed countries, which is
attributed to less widespread screening and a high rate of loss to follow up.

[Belhadj 2013]

Therefore, cervical cancer

screenings in these settings follows the screen-and-treat model. During this single visit, a speculum
examination is performed to visualize the cervix, followed by an application of 3% to 5% acetic acid to inspect

for characteristic acetowhite lesions. Cryosurgery is subsequently performed during that same visit for women
with abnormal examinations (Management Guidelines).

[USNCI Cervical]

In developed countries where providers and advanced testing modalities are widely available, women should
undergo cervical cancer screening that includes HPV testing and a Pap test every 6 months in the first year
after HIV diagnosis and annually thereafter(C) (Management Guidelines).

[CDC OI]

Although the current

recommendation for HIV-negative women is that a Pap test be performed every 3-5 years,
increased risk in HIV-infected women warrants more frequent screening.

[Massad 2012]

[Saslow 2012]

the

Many experts also

recommend colposcopy at initial HIV diagnosis as HIV-infected women may progress to cervical cancer at a
[Robinson 1997;Holcomb 1998]

faster rate.

A subsequent colposcopy should be based on cervical cytology results and

HPV DNA as outlined in Table 2.

[Cohn 2001;Goldie 2001; Harris 2005; Kitchener 2007]

Cervical cancer screening should be

performed annually regardless of age in women who were HIV-infected through sexual intercourse (C).

[CDC OI]

Table 2. Referral for Immediate Colposcopy According to Pap and HPV


DNA Risk
Pap Test Result
Normal

Abnormal
Normal
Abnormal

High Risk HPV DNA


(Subtypes 16 and 18)
Negative

Colposcopy
None indicated; continue
routine screening and
follow-up
Refer for colposcopy
Every 6 mos
Refer for colposcopy

Negative
Positive
Positive

The recommendations for colposcopy in Table 2 are based on studies with a small number of participants.
These studies have included comparisons between HIV-positive and HIV-negative women, assessment of
HIV-positive women at various stages of disease, comparisons between HIV-positive women receiving or not
receiving antiretroviral therapy, and considerations for cost-effectiveness. However, larger studies that
evaluate the long-term outcome in specific subgroups of women are needed.

In addition to cervical cancer, HPV infection can also result in anal intraepithelial neoplasia. Studies have
indicated increased prevalence and diversity of anal HPV infection in HIV-infected women compared with
uninfected women, providing additional support for routing screening for anal cancer.
2012]

[Mullins 2013; Kojic 2011b; Mallari

Anal Pap tests can be used as preliminary screening to detect anal neoplasia, although poor correlation

has been observed between anal cytology and high-resolution anoscopy.

[Mallari 2012]

Furthermore, abnormal

cervical cytology can be associated with the presence of abnormal anal cytology (relative risk: 1.7; P = .024),
and the positive predictive value of cervical Pap tests is poor when used to identify women with abnormal anal

cytology.

[Kojic 2011b]

Although there is no consensus for routine screening for anal cancer, the current guidelines

for the prevention and treatment of opportunistic infections suggest anal cytologic screening for HIV-infected
[CDC OI]

women, followed by high-resolution anoscopy in the case of abnormal cytologic results (C).

digital anal examination may also be useful in detecting masses that may be due to anal cancer.

Annual

[CDC OI]

There are currently 2 human papillomavirus vaccines approved by the US Food and Drug Administration for
the prevention of cervical cancer in HIV-negative females aged 9-26 years: a bivalent vaccine (subtypes 16
and 18) and a quadrivalent vaccine (subtypes 16 and 18 plus subtypes 6 and 11, the major causative agents of
genital warts). During vaccine development, clinical trials evaluating both efficacy and immunogenicity were
conducted in HIV-negative females with and without previous exposure to the specific HPV subtypes. Both the
bivalent and quadrivalent human papillomavirus vaccines demonstrated > 93% efficacy in preventing cervical
intraepithelial neoplasia and external genital lesions.

[FUTURE II 2007; Paavonen 2009]

In addition, both vaccines

generate robust and durable antibody responses to the HPV subtypes included. It is hoped that a human
papillomavirus vaccine will eliminate cervical cancer, and preliminary data indicate that the vaccine is safe and
immunogenic in HIV-positive women as well.

[Kojic 2014; Sow 2013; Kahn 2013; Firnhaber 2012]

Robust antibody titers were

observed in HIV-infected patients, with the bivalent vaccine eliciting higher titers of antibodies to HPV subtype
18 (similar to what has been observed in uninfected women).

[Toft 2014]

However, these studies have not

evaluated the overall efficacy of the human papillomavirus vaccine in this patient population. Primary care
guidelines from the HIV Medicine Association of the Infectious Diseases Society of America(Management
Guidelines)

[Aberg 2014]

and guidelines on the prevention of opportunistic infections in HIV-infected adults and

adolescents from the Centers for Disease Control and Prevention, the National Institutes of Health, and the
HIV Medicine Association of the Infectious Diseases Society of America (Management Guidelines)
OI]

[CDC

recommend human papillomavirus vaccine for all HIV-infected females 9-26 years of age (C).

Antiretroviral Therapy in HIV-Infected


Women
SUMMARY
Treatment Initiation

Selection of the initial ART regimen for women infected with HIV should be based
on (Management Guidelines)

[DHHS ART]

Childbearing potential and use of hormonal contraceptives

HIV serostatus of partners

Risk for adverse medication effects

Comorbidities

Anticipated adherence

Treatment Outcomes

Studies in antiretroviral-naive and antiretroviral-experienced patients have generally


demonstrated comparable response rates between men and women, although women are
generally underrepresented among trial populations

[Mocroft 2000; Moore 2003;Prins 2005; Collazos

2007; Hodder 2012; Mills 2009; Soon 2012; Patterson 2007]

There is some evidence that HIV-infected women are more likely to discontinue treatment
than men

[Currier 2010; Squires 2013]

Treatment Complications

Antiretroviral-associated adverse events are more frequent in women than men


2010; Mills 2009; Brinkman 1999; Bersoff-Matcha 2001; Mazhude 2002; Sanne 2005]

modify or discontinue ART because of adverse events

[Prins 2005; Molina

and women may be more likely to

[Lucas 1999]

Initiation of a nevirapine-containing regimen should be avoided in women with a CD4+ cell


3

count > 250 cells/mm due to increased risk for severe hepatotoxicity

[Hitti 2004]

Treatment Initiation
The standard US Department of Health and Human Services guidelines for initiation of antiretroviral therapy in
adults should be followed(Management Guidelines).
lower HIV-1 RNA level than men,

[DHHS ART]

Although women may progress to AIDS at a

[Sterling 2001]

antiretroviral therapy should be initiated in all patients to prevent

disease progression (B); the strength of this recommendation varies based on pretreatment CD4+ cell count.
In addition to the benefits to the woman herself, antiretroviral therapy also reduces the risk of mother-to-child
HIV transmission (see section on Antiretroviral Therapy in Pregnancy).

Selection of the initial antiretroviral therapy regimen for HIV-infected women should be based on

[DHHS ART]

Childbearing potential: Women wishing to conceive with an HIV-uninfected male partner have 2 primary
options for preventing HIV sexual transmission. The first is artificial insemination. The second option is
treatment with a maximally suppressive antiretroviral regimen. Women of childbearing potential should be
counseled on the potential risk associated with first trimester exposure toefavirenz; this drug may not be the
optimal choice for inclusion in an initial antiretroviral regimen in women of childbearing age who do not use
adequate contraception. Potential interactions between hormonal contraceptives and antiretroviral agents

should also be discussed and additional or alternative contraception used when appropriate. Safety and
pharmacology of newer agents, such asrilpivirine, dolutegravir,
and cobicistat/elvitegravir/emtricitabine/tenofovir, have not been evaluated in pregnancy. Of note, the most
vulnerable period for organogenesis is very early in gestation, often before pregnancy is recognized.

Serodiscordant couples: For serodiscordant couples wanting to conceive, use of antiretroviral therapy is
recommended for the HIV-infected partner. Conception should not be attempted until maximal viral
suppression is achieved. Pre-exposure prophylaxis (PrEP) for an HIV-uninfected partner can be offered as an
option for safer conception; however, the added benefit beyond viral suppression (and treatment of sexually
transmitted diseases) in the HIV-infected partner has been questioned.

[Hoffman 2013]

This requires counseling on

all available alternatives and lab testing for HIV infection, hepatitis B virus infection, and baseline renal function
prior to initiation ofemtricitabine/tenofovir as well as screening for sexually transmitted diseases. Adverse event
monitoring and HIV testing should be conducted during PrEP, and individuals should be continually aware of
the symptoms and potential for acute HIV infection. If HIV infection is identified, PrEP should be stopped
immediately and strategies to prevent perinatal transmission should be initiated if pregnancy has occurred; if
pregnancy has not occurred, conception attempts should be halted until further guidance from an HIV
specialist is obtained.

[DHHS Perinatal]

In either case, the patient should be immediately referred to an HIV

specialist.

Risk for specific complications: Antiretroviral-naive women with CD4+ cell counts > 250 cells/mm or
elevated baseline transaminase levels are at heightened risk of liver toxicity when taking nevirapine, and
therefore, a risk-benefit analysis should be conducted when considering nevirapine in this group of women.
Regardless of the regimen selected, women should be counseled on signs of lactic acidosis and evaluated for
this potential complication of antiretroviral therapy.

Other medical conditions: Individuals with elevated cardiovascular disease risk, for example, might wish to
avoid agents associated with dyslipidemia; individuals with osteopenia may wish to avoid agents associated
with greater reductions in bone mineral density.

Anticipated compliance: For individuals at increased risk of poor adherence, simpler antiretroviral therapy
regimens and those with few known adverse effects may be most appropriate. A discussion of how treatment
will be incorporated into a patients lifestyle should also be conducted, and any adverse events should be
proactively managed.

Additional factors to consider include potential drugdrug interactions with hormonal contraceptives, the
potential for depressed immunologic responses and increased comorbidities in older women, and drug-specific
data on effectiveness and adverse events in women.

[Greig 2014]

Despite these recommendations, considerable

numbers of HIV-infected women with clinical indications for treatment in the United States are not receiving
antiretroviral therapy. An analysis of factors associated with antiretroviral therapy use among 1354 HIVinfected women in the WIHS database who were clinically eligible for antiretroviral therapy in 2005 found that

approximately 30% were not receiving antiretroviral therapy.

[Lillie-Blanton 2010]

Black race and lack of health

insurance were each associated with reduced likelihood of antiretroviral therapy use in an adjusted analysis. Of
note, the results showed that women with publicly funded health insurance were more likely to receive
antiretroviral therapy than women with private health insurance. The reasons for this finding are not known;
potential causes include differences between public and private health programs regarding coverage levels,
support services provided, or HIV experience of participating physicians. These factors remain to be
investigated.

For additional information from inPractice on the timing and choice of first-line therapy in HIV, please click
here.

Treatment Outcomes
Outcomes from large treatment studies in both antiretroviral-naive and antiretroviral-experienced patients have
generally demonstrated nearly equivalent responses between men and women.
2003; Prins 2005; Collazos 2007]

[Castilho 2014; Mocroft 2000; Moore

However, some retrospective cohort studies in the United States and Canada have

found that women are statistically less likely than men to achieve virologic suppression after initiating
antiretroviral therapy.

[Cescon 2013; Althoff 2014]

One caveat among studies assessing this question is that the

percentage of female participants is limited to no more than 30%.

In recent years, the US Food and Drug Administration has required the development of postmarket analyses to
generate additional data on the efficacy of newly approved agents in populations underrepresented in pivotal
clinical trials. GRACE was the first study designed with the primary objective to compare treatment efficacy by
sex and race.

[Currier 2010]

This study demonstrated that there were no differences in virologic responses between

women and men receiving a darunavir/ritonavir-based regimen. Although efficacy did not vary, women were
more likely to discontinue therapy for reasons other than virologic failure despite the absence of statistically
significant sex-based differences in adverse events. The REALMRK study was conducted to evaluate efficacy
[Squires 2013]

outcomes with raltegravir-based therapy in women and black patients.

The overall results

demonstrated that virologic response rates were similarly high among women and men and among black and
nonblack patients. Similar to the GRACE trial, discontinuation rates were higher for women compared with
men.

Other treatment trials such as ECHO,

[Hodder 2012]

THRIVE,

[Hodder 2012]

and ARTEMIS

[Mills 2009]

also did not find sex-

based differences in treatment outcomes. However, these studies were not designed to detect sex differences.

The US Food and Drug Administration has completed a treatment efficacy meta-analysis that demonstrated
equivalent efficacy of antiretroviral therapy between men and women.

[Soon 2012]

In addition, virologic

suppression in women does not seem to vary by age. In an observational cohort analysis, the rate of virologic
response (HIV-1 RNA < 400 copies/mL) following 6 months of antiretroviral therapy was similar between men
and women, regardless of age category: 66% for men vs 67% for women younger than 50 years of age and
73% for men vs 78% for women 50 years of age or older (P = .68 for men vs women).

[Patterson 2007]

Immunologic

responses following antiretroviral therapy were also not affected by age or sex (P = .29). Furthermore, similar
responses were demonstrated in a clinical trials cohort of premenopausal and postmenopausal women.

[Patterson

2009]

Currently, there are 2 ongoing phase IIIb trials designed specifically to evaluate outcomes in treatment-naive
HIV-infected women. WAVES is a double-blind study comparing fixeddose cobicistat/elvitegravir/emtricitabine/tenofovir with ritonavirboosted atazanavir plusemtricitabine/tenofovir (Clinical Trial: NCT01705574), whereas ARIA is an open-label
investigation comparing fixed-dosedolutegravir/abacavir/lamivudine withritonavirboosted atazanavir plus emtricitabine/tenofovir (Clinical Trial: NCT01910402).

Treatment Complications
Despite similar efficacy profiles between men and women receiving antiretroviral therapy, women have a
higher risk for experiencing specific treatment-related complications including, most notably, rash and lactic
[Prins 2005]
acidosis. Overall, there are increased antiretroviral therapyassociated adverse events in women,
and
in some studies, HIV-infected women are more likely to modify or discontinue antiretroviral therapy because of
[Lucas 1999]
adverse events.
For example, women experienced more nausea and less diarrhea as compared with
[Molina 2010]
[Mills 2009]
men in both the CASTLE
and ARTEMIS
trials. These findings suggest that any subtle
differences in treatment outcomes may be related more to reduced treatment tolerability that is not captured in
the traditional grading categories. Studies are in progress to more carefully describe reasons why women are
[Currier
more likely than men to discontinue antiretroviral therapy in the absence of severe adverse events.
2000; Currier 2010]

Adverse events associated with NRTIs are more common in women and include lactic
acidosis[Brinkman 1999] hepatotoxicity, andzidovudine-associated complications (anemia). For NNRTIs,
associated adverse events more prevalent in women include rash[ref: BersoffMatcha 2001; Mazhude 2002] and
hepatotoxicity.[Sanne 2005] The initiation of a nevirapine-containing regimen should be avoided in
women with a CD4+ cell count > 250 cells/mm3 (and men with a CD4+ cell count > 400 cells/mm3)
as the risk for severe hepatotoxicity is increased.[Hitti 2004] Adverse events associated with PIs are
also more prevalent in women and include ritonavir intolerance. Data from a pharmacokinetic
study designed to compare sex differences showed that ritonavir levels were higher in women
compared with men; however, it is not clear whether these higher levels correlate to intolerance
in prospective studies.[Umeh 2011]
Two reports from ACTG studies suggest clinically important sex-based differences in the pharmacology of
antiretroviral drug combinations. A secondary objective in ACTG study A5202 was to evaluate the association
of sex on primary study outcomes of time to virologic failure, safety, and tolerability.

[Daar 2011; Smith 2014]

The

A5202 study randomized treatment-naive individuals to receive atazanavir/ritonavir orefavirenz with


either emtricitabine/tenofovir or abacavir/lamivudine. Women randomized to atazanavir/ritonavir had a 2.5-fold
higher rate of virologic failure compared with women randomized to efavirenz.

[Smith 2014]

These results have

clinical implications for women of childbearing potential who are more likely to be prescribed protease inhibitors
as a result of efavirenz pregnancy class D categorization. There was also the suggestion that male subjects
drove the previously reported emtricitabine/tenofovir superiority over abacavir/lamivudinein subjects with higher
HIV-1 RNA levels, and abacavir/lamivudine may have equivalent efficacy in women. Yet female participants
receivingabacavir/lamivudine were more likely to have grade 3/4 safety events than males.

The interim

[Campbell 2008]

and final analyses

[Campbell 2012]

of A5175 (PEARLS) also indicated differential treatment

responses to specific antiretroviral therapy regimens based on patient sex. The PEARLS study
compared lamivudine/zidovudine plus efavirenz vsemtricitabine/tenofovir plus efavirenz vs didanosine plus emt
ricitabine plus atazanavir in resource-limited settings. The regimen containing unboosted atazanavir was found
to have higher rates of treatment failure in a review by the data and safety monitoring board. In contrast to
A5202, women randomized to unboosted atazanavir were not found to have a higher rate of treatment failure
compared with men; instead, male sex was identified as a risk factor for treatment failure.
2012]

[Campbell 2008; Campbell

The difference in efficacy may be due to the decreased clearance of atazanavir (12 L/hr in women vs 14

L/hr in men), increased atazanavir exposure (34 mg*hr/L in women vs 30 mg*hr/L in men), and increased
maximum concentration of atazanavir (182 ng/mL in women vs 94 ng/mL in men) noted in the population
pharmacokinetic analysis from PEARLS
2008]

[Andrade 2011]

but also noted in previous studies.

[Squires 2004; Colombo 2006; Soals

These recent analyses lend further support to the need for additional women-focused treatment studies.

HIV-infected women develop different anthropometric changes after the initiation of antiretroviral therapy
compared with age-matched HIV-negative women. The FRAM study demonstrated that significantly more HIVinfected women compared with HIV-negative age-matched women experienced peripheral lipoatrophy (fat loss
in arms, cheeks, face, buttocks, and legs) (28% vs 4%, respectively; P < .001) (Capsule Summary).

[FRAM 2006]

In

addition, significantly fewer HIV-infected women experienced peripheral lipohypertrophy compared with
uninfected controls (35% vs 62%, respectively; P < .001). Central fat gain or lipohypertrophy was common in
both HIV-infected and control women, which is important because studies without control groups attribute all of
the central fat gain observed to HIV infection. Increased levels of serum triglycerides, leptin, and low density
lipoprotein cholesterol are also found in HIV-infected women.

[ref:Pernerstorfer Schoen 2001]

In general, however,

women are less likely to develop triglyceride elevations while receiving antiretroviral therapy. In the general
HIV population, insulin resistance has a very high prevalence ranging from 35% to 50%. There are no specific
studies demonstrating that women are at higher risk for insulin resistance. However, individuals who are
receiving PI therapy or who have developed lipodystrophy syndrome are thought to be at higher risk for insulin
resistance.

[Dube 2008]

DR. CARLOS RODOLFO MEJIA VILLATORO

MY SUBSCRIPTIONS

QUICK TOUR

MY CE

MY FOLDER

LOGOUT

Specialty

Decision Tools

Drug Reference

Guidelines

XGO

Specialty

HIV

Management of Specific Populations

HIV-Infected Women

Summary

Introduction

Primary Care of HIV-Infected Women

PubMed

Trials

More

Immunizations

Screening and Risk Factors

Reproductive Health Considerations

Oral Contraceptives

Injectable Contraceptives

Implantable, Intravaginal, and Intrauterine Contraceptives

Barrier Contraceptives

STDs

Cervical Cancer Screening

Antiretroviral Therapy

Treatment Initiation

Treatment Outcomes

Treatment Complications

Depression and HIV-Infected Women

Effect of Depression on ART and Outcomes

Treatment of Depression

Care of Pregnant HIV-Infected Women

HIV Screening in Pregnant Women

Initial Evaluation

ART During Pregnancy

Monitoring During Pregnancy

Immunizations

Intrapartum Management

Mode of Delivery

Concurrent ART and Other Medications

Postpartum Management

Care of Menopausal HIV-Infected Women

Age of Menopause

Symptoms of Menopause

Treatment of Menopause Symptoms

Additional Considerations

Primary Care Essentials

Supporting Assets

References

Jointly Sponsored by inPractice Resources, LLC, and:

more information about our sponsors

Previous

Next

Save

Share

Print

Email

Special Considerations in the Management of HIV-Infected Women, Including


Management of Conception and Pregnancy

Author: Kristine Patterson, MD (More Info)

Section Editor: Judith S. Currier, MD, MSc

Editors in Chief: Joseph J. Eron, Jr., MD; Daniel R. Kuritzkes,


MD; Kathleen E. Squires, MD

Last Reviewed: 4/24/14 (What's New)

Depression and HIV-Infected Women


SUMMARY

Depressive symptoms or disorders are common in


women infected with HIV
2002]

[Ickovics 2001; Cook 2002a; Morrison

Depression screening should be incorporated into


routine clinical care for this population

Effect of Depression on Antiretroviral Treatment


and Overall Clinical Outcomes

Access to pharmacologic and psychiatric


therapy increases use of ART among HIVinfected women with depression

[Cook 2006]

HIV and depression can be treated


[Cook 2006; Himelhoch 2007]

concurrently

Although preexisting depression is not a


contraindication for efavirenz use, vigilant
observation for development of psychiatric
problems is advised when
initiating efavirenz in women with a history
of mental health problems

Treatment of Depression in Women With HIV

Initiation of an antidepressant in women


receiving ART should involve consideration
of potential drug interactions

HIV-infected patients should receive


ongoing screening for depression, with
referral for appropriate mental health
intervention when indicated

Within the general population and among persons infected with HIV, women have a higher rate of depression
than men. Approximately 50% of HIV-infected womennearly double that of HIV-infected menhave
characteristics consistent with depressive symptoms or disorders.

[Ickovics 2001; Cook 2002a]

In addition, 1 in 5 HIV-

infected women meet the classification for major depressive disorders compared with 1 in 20 HIV-negative
women.

[Morrison 2002]

Although the diagnosis of depression in HIV-infected women is common, the underlying

etiologies of the depression diagnosis often require formal psychiatric or mental health counseling to overcome
the disorder. Given the frequency of depression in this population, depression screening should be
incorporated into routine clinical care. Screening tools such as the Edinburgh Postnatal Depression Scale may
be useful in detecting antenatal depression in HIV-infected women.

[Rochat 2013]

Depression is sometimes

associated with domestic violence and therefore screening for past or ongoing intimate partner violence may
also be clinically relevant.

[Illangasekare 2013a; Illangasekare 2013b]

Effect of Depression on Antiretroviral Treatment and Overall Clinical


Outcomes
[Ickovics 2001; Ironson 2005]

Depression may

or may not

[Evans 2002; Anastos 2005; Cruess 2005; Alciati 2007]

affect immunologic

recovery following initiation of antiretroviral therapy. Individuals with depression may have a diminished
[Anastos 2000]

virologic response

and time to virologic suppression may be increased.

[Pence 2007]

Access to

pharmacologic and psychiatric therapy increases the use of antiretroviral therapy among HIV-infected women
with depression.

[Cook 2006]

In addition, there is a significant association between intimate partner violence and

the incidence of HIV infection among women.

[Li 2014]

Furthermore, women with HIV infection who are exposed to

intimate partner violence have lower rates of adherence to antiretroviral treatment, particularly those who score
lower on resilience assessment tests.

[Dale 2014]

Clinicians should be mindful of potential exposure to domestic

violence in all women at entry to care, when adherence patterns change, and if concern for depression
emerges. Women should be made aware and linked to appropriate support services.

Women with depression have increased rates of all-cause and AIDS-related mortality and new AIDS-defining
illnesses.

[Cook 2002b]

substance abuse.

Untreated depression may result in higher rates of sexually transmitted infections and

[Chander 2006; Berg 2007]

function in HIV-infected women.

Depression has also been shown to correlate with decreased cognitive

[Fialho 2013]

Individuals who are receiving ongoing treatment for depressive

disorders appear to have similar responses to antiretroviral therapy, supporting the concurrent treatment of HIV
and depression.

[Cook 2006; Himelhoch 2007]

Neuropsychiatric complications related to the use of antiretroviral medications, ranging from vestibular
symptoms and sleep disorders to frank psychosis, have been documented in several case reports of various
complications with zidovudine,
2004]

and nevirapine,

of efavirenz.

[Wise 2002]

[Maxwell 1988; ref:O Dowd 1988;Schaerf 1988]

abacavir,

[Colebunders 2002; Foster

although the most extensive body of literature details neuropsychiatric effects

[Cespedes 2006; Efavirenz PI; Clifford 2005]

Some of these studies have suggested that individuals with a

history of mental health problems may be at an increased risk of developing such complications
of efavirenz use; however, the studies are contradictory and inconclusive. Regardless, although many
providers will be hesitant to use efavirenz in women with a diagnosis of depression, preexisting depression is
not a contraindication for efavirenz use. If used, vigilant observation for the development of psychiatric
problems when initiating therapy with efavirenz-containing regimens is advised in women with a history of
mental health problems.

Treatment of Depression in Women With HIV

Efficacy trials of antidepressant use in HIV-infected women are lacking. In a study that included mostly HIVinfected men (83%), depressed patients compliant with selective serotonin reuptake inhibitor (SSRI) use
adhered to their antiretroviral therapy regimens and achieved viral control that was statistically similar to
nondepressed HIV-infected patients receiving antiretroviral therapy. Furthermore, depressed patients
compliant with SSRI treatment had statistically significantly greater immunologic responses when compared
with depressed patients who were noncompliant with their SSRI regimen.

[Horberg 2008]

Before initiating any

antidepressant agent in women receiving antiretroviral therapy, care must be taken to make sure there are no
metabolic interactions that may increase adverse effects or diminish the efficacy of either agent.

Although depression is a common mental health issue in HIV-infected women, there is a growing body of
evidence demonstrating the efficacy of antiretroviral therapy in improving depressive symptoms.
2000]

[Judd 2000; Low-Beer

Moreover, treating depression improves HIV outcomes. Therefore, positive mental health and HIV

outcomes can be achieved when the 2 diagnoses are addressed concurrently. Ongoing screening for
depression should be used in the clinical setting with referral for appropriate mental health intervention when
indicated.

For additional information from inPractice on psychiatric disorders in HIV-infected patients, click here.

Keywords: Neurologic Complications, Psychiatric Disorders, Women

DR. CARLOS RODOLFO MEJIA VILLATORO

MY SUBSCRIPTIONS

QUICK TOUR

MY CE

MY FOLDER

LOGOUT

Specialty

Decision Tools

Drug Reference

Guidelines

XGO

Specialty

HIV

Management of Specific Populations

HIV-Infected Women

Summary

Introduction

Primary Care of HIV-Infected Women

PubMed

Trials

More

Immunizations

Screening and Risk Factors

Reproductive Health Considerations

Oral Contraceptives

Injectable Contraceptives

Implantable, Intravaginal, and Intrauterine Contraceptives

Barrier Contraceptives

STDs

Cervical Cancer Screening

Antiretroviral Therapy

Treatment Initiation

Treatment Outcomes

Treatment Complications

Depression and HIV-Infected Women

Effect of Depression on ART and Outcomes

Treatment of Depression

Care of Pregnant HIV-Infected Women

HIV Screening in Pregnant Women

Initial Evaluation

ART During Pregnancy

Monitoring During Pregnancy

Immunizations

Intrapartum Management

Mode of Delivery

Concurrent ART and Other Medications

Postpartum Management

Care of Menopausal HIV-Infected Women

Age of Menopause

Symptoms of Menopause

Treatment of Menopause Symptoms

Additional Considerations

Primary Care Essentials

Supporting Assets

References

Jointly Sponsored by inPractice Resources, LLC, and:

more information about our sponsors

Previous

Next

Save

Share

Print

Email

Special Considerations in the Management of HIV-Infected Women, Including


Management of Conception and Pregnancy

Author: Kristine Patterson, MD (More Info)

Section Editor: Judith S. Currier, MD, MSc

Editors in Chief: Joseph J. Eron, Jr., MD; Daniel R. Kuritzkes,


MD; Kathleen E. Squires, MD

Last Reviewed: 4/24/14 (What's New)

Care of Pregnant HIV-Infected Women


SUMMARY

DHHS recommends use of ART by all HIV-infected


pregnant women to reduce the risk of mother-to-

child transmission of HIV(Management


Guidelines)

[DHHS Perinatal]

Screening for HIV in Pregnant Women

CDC guidelines recommend routine


prenatal HIV screening in the first trimester
in all pregnant women, with consideration
of repeat testing in the third
trimester (Management Guidelines)

[CDC

Testing 2006]

Women who present to labor and delivery


with unknown HIV status or who are at risk
for HIV should undergo rapid HIV testing

Women with a positive rapid test should


receive intravenous zidovudine without
waiting for confirmation of HIV status

Initial Evaluation of Pregnant HIV-Infected


Women

Medical care of pregnant women infected


with HIV should involve both obstetrical
providers and HIV specialists

Pregnant women should be counseled to


avoid tobacco and illicit drug use,
encouraged to use condoms during sexual
intercourse, and screened for genital tract
infections, HBV, HCV, and TB

Antiretroviral Therapy During Pregnancy

ART should be initiated in all HIV-infected


pregnant women regardless of CD4+ cell
count or HIV-1 RNA level

Resistance testing, CBC, and renal and


liver function testing should be obtained
before treatment initiation

Appropriate OI prophylaxis should be


started based on CD4+ cell count

Selection of ART should be made in


consultation with an expert provider and
based on treatment guidelines (Table
3)

[DHHS Perinatal; DHHS ARV Safety]

Initiation of ART can be delayed until after


the first trimester for women receiving ART,
primarily for fetal protection

Women who become pregnant while


receiving an efavirenz-containing ART
regimen do not require a change in ART

Monitoring During Pregnancy

HIV-infected pregnant women should be


monitored with greater frequency for
treatment response and
complications(Management
Guidelines)

[DHHS Perinatal]

Immunizations

HIV-infected pregnant women should follow


the same vaccination schedule as
nonpregnant HIV-infected individuals, with
particular attention to the need for hepatitis
A and B vaccination (if antibodies are not
present) and [drug: influenza virus vaccine,
inactivated]

Intrapartum Management

IV zidovudine near delivery is


recommended for HIV-infected pregnant
women with HIV-1 RNA > 1000 copies/mL
or unknown HIV-1 RNA levels unless there
is evidence of resistance or
toxicity (Management Guidelines)

[DHHS

Perinatal]

Neonatal zidovudine prophylaxis for 6


weeks is also recommended

[DHHS Perinatal]

Mode of Delivery

Women whose HIV-1 RNA


remains > 1000 copies/mL near
the time of delivery should be
advised to undergo Cesarean
section(Management
Guidelines)

[DHHS Perinatal]

It is unclear if scheduled Cesarean


section delivery would provide
additional reduction in perinatal
transmission risk for women
receiving antiretroviral therapy
with HIV-1 RNA 1000 copies/mL

Invasive fetal monitoring,


operative delivery with vacuum
devices or forceps, and artificial or
prolonged rupture of membranes
should be avoided in HIV-infected
women

[Mofenson 1999; Shapiro 1999]

Concurrent Antiretroviral Therapy and


Other Medications

Women should continue their oral


ART regimen as prescribed before
and during labor and

delivery (Management
Guidelines)

[DHHS Perinatal]

Intravenous zidovudine infusion


should replace
[DHHS Perinatal]

oral zidovudine

Methylergonovine should be
avoided in women receiving PIs
or efavirenz

HIV-infected women who present


to labor and delivery who are not
receiving ART, or women who
have a positive rapid HIV test at
labor and delivery, should initiate
IV zidovudine as soon as possible
and undergo Cesarean section
[DHHS Perinatal]

delivery

Postpartum Management

Continuation of ART postpartum is


recommended unless a contraindication
exists (Management Guidelines)

[DHHS

Perinatal]

However, decisions regarding


ART continuation postpartum
should be made with consultation
between the woman and her HIV
provider, preferably before
delivery

ART may be simplified to increase


adherence

Breastfeeding is currently not


recommended in any HIV-infected women
with access to clean water and formula,
regardless of HIV-1 RNA level

[DHHS Perinatal]

During the past 25 years, guidelines for the treatment of HIV-infected pregnant women and prevention of
perinatal transmission have evolved considerably. The current recommendations focus on ensuring use
of antiretroviral therapy by known HIV-infected pregnant women, regardless of maternal health needs, to
reduce the risk of mother-to-child transmission; identifying HIV infection in pregnant women with previously
undiagnosed or newly acquired HIV infections; preventing HIV transmission to infants through the use of
chemoprophylaxis antiretroviral therapy; and avoiding breastfeeding. These recommendations have resulted in
a significant decrease in perinatal transmission ratesto less than 2%in the United States and the United
Kingdom.

[Townsend 2008]

The US Department of Health and Human Services guidelines provide an overview of

the most common circumstances that occur in the care of HIV-infected pregnant women (Management
Guidelines).

[DHHS Perinatal]

Screening for HIV in Pregnant Women


Current Centers for Disease Control and Prevention guidelines recommend routine prenatal HIV screening in
the first trimester in all women and repeat testing in the third trimester of pregnancy may also be
considered (C) (Management Guidelines).

[CDC Testing 2006]

Repeat testing in the third trimester of pregnancy is

recommended in areas of high HIV prevalence, women at high risk for HIV infection, or women with symptoms
of acute HIV infection.

[CDC Testing 2006]

This repeat testing is supported by recent evidence that showed an

incidence rate of 16.75 per 1000 person-years during pregnancy in a group of women in Swaziland who were
HIV negative at initial testing. In total, 4.4% of women who were HIV negative at study entry were HIV positive
at the time of delivery.

[Kieffer 2011]

Other studies have shown higher rates of HIV acquisition in pregnant women

(2.3 per 1000 person-years) when compared with nonpregnant (1.1 per 1000 person-years) or lactating (1.3
per 1000 person-years) women.

[Gray 2005]

These data suggest that pregnant women may be at increased risk for

HIV transmission and that repeat testing is warranted in sexually active women during pregnancy.

Women who present to labor and delivery with unknown HIV status or who are at risk for HIV should undergo
rapid testing. Those with a positive rapid test should receive intravenous zidovudine (A). Initiation
of zidovudine should not be delayed for testing confirmation.

Initial Evaluation of Pregnant HIV-Infected Women


The medical care of an HIV-infected pregnant woman should integrate the expertise of the obstetrical providers
and the HIV specialists to decrease the risk of HIV transmission and obstetrical complications. Known
behavioral risk factors that increase the risk of perinatal HIV transmissionat least in studies conducted before
the antiretroviral therapy erainclude

[Burns 1994; Matheson 1996; Rodriguez 1996;Bulterys 1997; Turner 1997]

Cigarette smoking

Illicit drug use

Genital tract infections

Unprotected intercourse with multiple partners during


pregnancy

Therefore, counseling to avoid tobacco and illicit drug use, encouraging the use of condoms during sexual
intercourse, and screening for genital tract infections should be integrated into care.

Biological factors associated with perinatal transmission of HIV are primarily determined by maternal health.
These factors include:

Past and present CD4+ cell counts

Plasma HIV-1 RNA

Antiretroviral resistance

Past and present opportunistic infections

Initial management should also include screening for hepatitis B virus, hepatitis C virus, and tuberculosis. A
thorough history of adverse effects during previous antiretroviral regimens should also be gathered.

Antiretroviral Therapy During Pregnancy


Antiretroviral therapy should be initiated in all HIV-infected pregnant women regardless of CD4+ cell count or
HIV-1 RNA level (A). Some women require antiretroviral therapy only for fetal protection whereas others also
require antiretroviral therapy for maternal health. In either circumstance, antiretroviral resistance testing should
be obtained before initiating antiretroviral therapy. Complete blood cell count and renal and liver function
testing should also be obtained before treatment initiation. Appropriate opportunistic infection prophylaxis
should be started based on current CD4+ cell count.

Decisions regarding which antiretroviral combinations are most effective in pregnancy are complex and should
be made in consultation with a provider who has an understanding of these complexities (Table 3).
Perinatal; DHHS ARV Safety]

[DHHS

The efficacy of antiretroviral therapy in preventing maternal-fetal transmission is primarily

through lowering plasma HIV-1 RNA but also due to pre-exposure prophylaxis (PrEP) for the infant. The
mechanism by which infant PrEP is effective is through antiretroviral agents crossing the placenta, resulting in
adequate systemic concentrations in the infant. This is especially important at the time of delivery when the
infant is exposed to maternal blood and genital tract secretions. Because transmission can occur in women at
any plasma HIV-1 RNA level, including those with undetectable plasma HIV-1 RNA, all HIV-infected pregnant
women should be offered antiretroviral therapy. One or more NRTIs with high levels of transplacental passage

should be used. Antiretroviral therapy should be initiated as soon as possible in pregnant women who have
indications for antiretroviral therapy. Initiation of antiretroviral therapy can be delayed until after the first
trimester for women receiving antiretroviral therapy for fetal protection, but earlier initiation is more effective in
preventing transmission. Data from a recent study involving 806 infants found that infants exposed to
antiretroviral therapy during the first trimester of pregnancy did not have an increased risk of birth defects
compared with unexposed infants (odds ratio: 1.07; 95% CI: 0.50-2.31).

[Phiri 2014]

For women who remain

viremic during pregnancy or are diagnosed with HIV late in pregnancy, a raltegravir-containing regimen can
rapidly decrease viral load.
antiretroviral therapy.

[Westling 2012]

There is no evidence that pregnancy decreases the efficacy of

[Rachas 2013]

The recommendations for initiation of antiretroviral therapy for maternal health are similar between pregnant
and nonpregnant HIV-infected women; however, additional factors specific to pregnancy must be considered.

For women who are pregnant, a regimen with at least 3


agents is recommended; the regimen should be
individualized based on previous antiretroviral therapy and
any comorbidities. For antiretroviral-naive women who are
pregnant, a combination regimen with 2 NRTIs
(eg, lamivudine-zidovudine) and either an NNRTI or a
boosted PI is preferred. Although zidovudine has historically
been the preferred NRTI for pregnant women, alternative
agents can be considered for women who have
developed zidovudine-related toxicity, such as severe
anemia, or who have resistance to the drug. Some experts
prefer to use different NRTIs such as emtricitabinetenofovirbecause they wish to avoid zidovudine-associated
adverse events such as nausea and anemia, which may be
problematic in pregnancy. Triple-NRTIonly regimens should
be avoided.

Women should be counseled regarding the potential risk of


congenital anomalies in infants exposed to efavirenz in the
first trimester. However, there are conflicting data as to the
true risk. Two reports have not supported an increased risk
in efavirenz-exposed infants than in the general
population

[APRSC 2013; Ford 2010]

an increased risk.

[Brogly 2010]

whereas others have suggested

Current practices suggest that efavirenz should be avoided in


the first trimester of pregnancy and possibly avoided in
women of childbearing potential who do not practice reliable
birth control who have alternative choices of antiretroviral
agents. However,efavirenz may be a preferred choice in
some women, such as in a late diagnosis of HIV and the
need for rapid viral decay or those with tuberculosis
coinfection.

[Torti 2008; WHO 2010]

Because neural tube defects develop in the first 5-6 weeks of


pregnancy and unnecessary antiretroviral regimen changes
during pregnancy can result in loss of viral control and
increased risk of perinatal transmission, efavirenz can be
continued in women who present for care in the first trimester
if they are virologically suppressed.

[DHHS Perinatal]

Typically, the most appropriate course of action for HIVinfected women who are virologically suppressed on
antiretroviral therapy and subsequently become pregnant is
to continue the current antiretroviral regimen, regardless of
agent(s) because of the (small) risk of virologic breakthrough
that may accompany any regimen modification.

Some NRTIs, such as zidovudine, have demonstrated


increased efficacy in preventing transmission independent of
their antiviral effects because of the high levels of
transplacental passage. Therefore, antiretroviral regimens
should include 2 NRTIs with high levels of transplacental
passage (zidovudine, lamivudine, emtricitabine, tenofovir,
or abacavir). As stated above, triple-NRTIonly regimens
should be avoided.

Consider other comorbid conditions, such as hepatitis B, and


possible adverse outcomes for mother and fetus when
choosing antiretroviral regimens.

Recent data show that PI use is associated with preterm


delivery but not increased hospitalizations or infant mortality.
PI use is proven to be beneficial, but clinicians should be
aware of this potential risk and be prepared to manage the

patients appropriately to maximize benefits of antiretroviral


therapy during pregnancy.

[Powis 2011]

Potential adverse events and the womans ability to adhere to


a particular regimen during pregnancy should be
considered.

[DHHS ART]

Table 3. Recommendations for Use of Antiretroviral Agents in


Pregnancy[DHHS Perinatal]
Category

NRTI
Preferred

Antiretroviral Therapy

Abacavir/lamivudine

Emtricitabine/tenofovir ortenofovir/lamiv
udine

Lamivudine/zidovudine

Not
recommend
ed

Abacavir/lamivudine/zidovudine

Didanosine

Pregnan
cy Drug
Class

Additional
Considerations

C/C

Abacavir should
not be used in
patients who test
positive for HLAB*5701.
QD administration.
Potential renal
toxicity
with tenofovir; use
with caution in
patients with renal
insufficiency.
NRTI combination
that has most
experience in
pregnancy.
Disadvantages
include BID
dosing and
potential for
increased
hematologic
toxicity.
Inferior virologic
efficacy.

B/B or
B/C

C/C

C/C/C

Not recommended
because of toxicity.

NNRTI
Preferred

Stavudine

Not recommended
because of toxicity.

Efavirenz

Initiate after first 8


wks of pregnancy.
Can be continued
in pregnant women
presenting earlier
in first trimester
with undetectable
HIV-1 RNA.
Concern for
association with
birth defects based
on primate study;
however, risk in
humans unclear.
Ensure postpartum
contraception.

Alternative

Nevirapine

Insufficient
data

Rilpivirine

Preferred in
women who
require
concomitant use of
drugs that interact
with PIs.
Use with caution in
women who are
starting ART with
baseline CD4+ cell
count > 250
cells/mm3 due to
hepatotoxicity. Use
with caution in
combination
with abacavirbecau
se both agents can
cause
hypersensitivity
reaction within
first few wks of
treatment.
Limited data. Not
recommended with
baseline HIV-1
RNA > 100,000

Not
recommend
ed
PI
Preferred

Etravirine

Atazanavir/ritonavir

copies/mL or
CD4+ cell count <
200 cells/mm3. Do
not use in
combination with
proton pump
inhibitor.
Not recommended
in ART-naive
patients.

B/B

Should be given as
boosted regimen.
QD administration.
Some experts
recommend
increased dosing
during the second
and third
trimesters.
The package insert
recommends
increased dosing
only for:

ART-experienced
pregnant women
in the second
and third
trimesters also
receiving
either tenofovir or
an H2-receptor
antagonist (not
both), or
ART-naive
pregnant women
also
receivingefaviren
z.
Should not be used
in ARTexperienced

Lopinavir/ritonavir

Ritonavir

Alternative

Darunavir/ritonavir

C/B

C/B

pregnant patients
receiving
both tenofovir and
H2-receptor
agonists or in
antiretroviralexperienced
patients also
taking efavirenz or
proton-pump
inhibitors.
Avoid QD dosing
during pregnancy.
Unclear if dose
increase to 3
tablets BID in
second and third
trimester is
necessary in ARTnaive patients.[Patterson
2013]
Closely monitor
virologic response
and lopinavir level
s if standard dosing
used in PIexperienced
patients.
Should only be
used in
combination with
second PI as lowdose ritonavir boo
st to increase
levels of second
PI.
Limited data.[Zorrilla
2014]
May be
considered when
preferred agents
cannot be used.
Must boost with
low-dose ritonavir.

Not
recommend
ed

Insufficient
data
Entry
inhibitors
Insufficient
data
Not
recommend
ed
Integrase

Saquinavir/ritonavir

B/B

Indinavir/ritonavir

C/B

Nelfinavir

Tipranavir

Fosamprenavir/ritonavir

C/B

Limited
pharmacokinetic
data
on saquinavir in
pregnancy.
Baseline
electrocardiogram
recommended
before initiating
treatment based on
potential for PR
and QT
prolongation;
contraindicated
with preexisting
cardiac conduction
system disease.
Large pill burden.
Not recommended
because of BID
dosing, pill burden,
and potential for
renal stones,
hyperbilirubinemia
.
Previous reports of
ethyl methane
sulfonate
contamination
have been
resolved. Inferior
virologic efficacy.
Not recommended
in ART-naive
patients.
Limited data.

Maraviroc

Limited data.

Enfuvirtide

Not recommended
in ART-naive
patients.

inhibitors
Alternative

Insufficient
data

Raltegravir

Dolutegravir
Cobicistat/elvitegravir/emtricitabine/teno
fovir

B
B

Limited data; can


be considered for
use in special
circumstances
when preferred
agents cannot be
used, particularly
when drug
interactions with
PIs are a concern.
Limited data.
Limited data.

ART, antiretroviral therapy; BID, twice daily; QD, once daily.

Monitoring During Pregnancy


HIV-infected pregnant women require additional considerations during pregnancy. Those
receiving antiretroviral therapy (ART) should be monitored regularly for treatment response and
complications (Management Guidelines).

[DHHS Perinatal]

Ultrasound

First trimester ultrasound is recommended for confirmation of


gestational age

Second trimester ultrasound is recommended to assess fetal


anatomy

Laboratory monitoring

Complete blood cell count to evaluate for anemia, especially


if taking zidovudine

Renal toxicity

Serum bicarbonate, especially if


receiving didanosine or stavudine, to evaluate for lactic
acidosis (neither of these drugs is recommended as a firstline agent in pregnancy)

Liver function tests

HIV-1 RNA levels should be monitored 2-4 weeks after


initiating or changing ART, monthly thereafter until HIV-1
RNA is undetectable, and then at least every 3 months. At

approximately 34-36 weeks gestation, HIV-1 RNA should be


assessed such that decisions regarding mode of delivery or
alterations in ART before delivery can be made

CD4+ cell count should be monitored every 3 months

Can be reduced to every 6 months in patients with consistent


viral suppression and CD4+ cell counts well above threshold
for opportunistic infection risk

Antiretroviral resistance testing should be performed:

Before initiating ART in treatment-naive women with HIV-1


RNA higher than the threshold for resistance testing (> 5001000 copies/mL) if they have not received previous
resistance testing

Before initiating ART in women who received antiretroviral


agents to prevent perinatal transmission in previous
pregnancies and who are reinitiating antiretroviral agents for
preventing perinatal transmission if HIV-1 RNA levels are
higher than the threshold for resistance testing (> 500-1000
copies/mL)

Before changing ART regimens in women who become


pregnant with HIV-1 RNA higher than the threshold for
resistance testing (> 500-1000 copies/mL) while receiving
ART or with persistently detectable HIV-1 RNA after initiating
ART during pregnancy

Hyperglycemia

Although pregnancy itself is associated with hyperglycemia,


the use of PIs does not appear to increase this risk

Women should receive standard glucose screening with a


standard 1-hour, 50-gram glucose loading test at 24-28
weeks

Earlier testing should be considered in women with risk


factors for glucose intolerance such as PI therapy, obesity,
advanced maternal age, and family history of diabetes

Metabolic alterations are common during pregnancy and can be complicated by ART. Clinicians should closely
monitor patients during pregnancy, tailoring treatment and recommending lifestyle alterations to manage
metabolic conditions that can affect both the mother and infant.

[Guaraldi 2014]

For additional information from inPractice on laboratory assays used in patient monitoring, click here.

Immunizations
The immunization history of HIV-infected pregnant women should be reviewed at the initial prenatal visit.
Women should follow the same vaccination schedule as nonpregnant HIV-infected individuals with special
attention given to make sure HIV-infected women are vaccinated against hepatitis A and B (if antibodies are
not present) and influenza. Because HIV-infected persons and pregnant women are each individually at
increased risk for influenza-related complications, HIV-infected pregnant women should be strongly
encouraged to receive the [drug: influenza virus vaccine, inactivated].

Intrapartum Management
The PACTG 076 trial demonstrated that the use of zidovudine (antepartum, intravenous zidovudine during
delivery and in the infant) decreased perinatal transmission by 67.5%.

[Connor 1994]

As a result,

intravenous zidovudine during labor and delivery (regardless of mode of delivery) is still highly
recommended for women with HIV-1 RNA > 1000 copies/mL or unknown HIV-1 RNA levels unless there is
evidence of resistance or toxicity (A) (Management Guidelines).

[DHHS Perinatal]

For women who are virologically

suppressed consistently during late pregnancy and for whom there are no adherence concerns, current
antiretroviral therapy does not require the addition of intravenous zidovudine. However, every effort should be
made to administer zidovudine in appropriate patients. Neonatal zidovudineprophylaxis for 6 weeks is also
recommended.

[DHHS Perinatal]

Mode of Delivery
Women whose HIV-1 RNA remains > 1000 copies/mL should be recommended to undergo Cesarean section,
whereas it is unclear if Cesarean section delivery confers added benefit in women receiving antiretroviral
therapy with plasma HIV-1 RNA 1000 copies/mL(Management Guidelines).

[DHHS Perinatal]

In women with HIV-1

RNA > 1000 copies/mL, a Cesarean section should be scheduled at 38 weeks of gestation, if possible.
Intravenous zidovudine should be used, with infusion initiated 3 hours before the scheduled Cesarean section
delivery (2 mg/kg over 1-hour loading dose, then 1 mg/kg/hour continuous infusion until delivery, ie, umbilical
cord ligated).
In women whose HIV-1 RNA is 1000 copies/mL, Cesarean section delivery required for standard obstetric
indications should be performed at 39 weeks of gestation. Invasive fetal monitoring or operative delivery with
vacuum devices or forceps should be avoided in HIV-infected women, as these may increase risk of
transmission.

[Mofenson 1999; Shapiro 1999]

Likewise, artificial or prolonged rupture of membranes should be avoided,

and women should be moved toward Cesarean section delivery if labor does not progress 4 hours after
membranes have ruptured (C). Intravenous infusion with zidovudine should be initiated at the onset of labor,
using the dosing schedule outlined for Cesarean section.

Concurrent Antiretroviral Therapy and Other Medications


Women should continue their oral antiretroviral therapy regimen as prescribed before and during the
[DHHS Perinatal]

labor/delivery process (Management Guidelines).

The intravenous zidovudine infusion should

replace oral zidovudine. Therefore, women receiving a fixed-dose combination pill


of lamivudine/zidovudine should receive lamivudine 150 mg every 12 hours rather than
the lamivudine/zidovudinecombination pill formulation. Additional antiretroviral agents should be administered
as prescribed with the exception of stavudine.Zidovudine and stavudine are antagonistic and, therefore, should
not be used concurrently. Methylergonovine should be avoided in women receiving PIs or efavirenz because of
the risk of exaggerated vasoconstrictive responses. If absolutely required, the lowest possible dose
ofmethylergonovine should be used.

Additional considerations should be taken in the following scenarios.

Women who present to labor and delivery who are not receiving antiretroviral therapy:

Intravenous zidovudine infusion (2 mg/kg loading dose


followed by 1 mg/kg/hour continuous infusion) should be
initiated as soon as possible

Women should undergo Cesarean section delivery

Infants should receive zidovudine for 6 weeks unless testing


confirms positivity

Infants of mothers with suboptimal viral suppression may also


receive a full antiretroviral therapy regimen

Women who have positive rapid HIV testing at labor and delivery:

Intravenous zidovudine infusion (2 mg/kg loading dose


followed by 1 mg/kg/hour continuous infusion) should be
initiated as soon as possible

Women should undergo Cesarean section delivery

Confirmation testing should be completed after delivery

Infants should receive zidovudine until the mothers HIV


status is confirmed and infant test results are confirmed

Postpartum Management
Current recommendations highlight the need for antiretroviral therapy for all HIV-infected patients, because
untreated HIV infection or uncontrolled viremia may be associated with adverse outcomes including increased
risk of cardiovascular disease, liver disease, and neurologic complications (Management Guidelines).
ART]

[DHHS

Moreover, the SMART study demonstrated that among patients with a prior CD4+ cell count < 350
3

cells/mm , interrupting antiretroviral therapy is associated with an increased risk of immunologic impairment
resulting in risk of opportunistic disease or death from any causeas well as a higher risk of AIDS-defining
[El-Sadr 2006;Lundgren 2008; Silverberg 2007]

malignancies.

Therefore, there is no longer a solid rationale to stop

antiretroviral therapy in the postpartum period. However, decisions regarding the continuation of antiretroviral
therapy postpartum should involve consultation between the woman and her HIV provider, preferably before
delivery, and with the following considerations in mind (Management Guidelines)

[DHHS Perinatal]

The option of continuing antiretroviral therapy in women who


initiated antiretroviral therapy for fetal protection should be
recommended unless a contraindication exists; however,
antiretroviral therapy may be simplified to increase adherence

Women who received an NNRTI (nevirapine or efavirenz) and


elect to discontinue antiretroviral therapy after delivery should
discontinue the NNRTI while continuing the other
antiretroviral agents (NRTIs) for an additional week to
decrease the risk of NNRTI resistance. Alternatively, a PI
may be substituted for the NNRTI for 7 days and then all
antiretroviral therapy discontinued simultaneously. Women
whose antepartum regimen did not include an NNRTI and
who plan to discontinue antiretroviral therapy after delivery
can stop all drugs simultaneously

Adherence to antiretroviral therapy should be reinforced


postpartum as it often decreases during this period; clinicians
should evaluate patients for issues that may reduce
adherence (eg, depression or drug and alcohol use)

Breastfeeding is not recommended in any HIV-infected women with access to clean water and formula,
regardless of HIV-1 RNA level, because of the increased risk of HIV transmission (C).

[DHHS Perinatal]

However, in

settings that lack such access and where breastfeeding is required for infant health, data from the PROMOTE
study comparing efavirenz plus lamivudine/zidovudine withlopinavir/ritonavir plus lamivudine/zidovudine in 389
pregnant women in rural Uganda are informative. Antiretroviral therapy was initiated at 12-28 weeks of
gestation and continued to 1 year or throughout breastfeeding (women were counseled to breastfeed for 1
year). A recent subanalysis of the study revealed a very low HIV transmission rate of 0.5% among live-born
infants, including only 1 case of transmission during breastfeeding, which occurred in the lopinavir/ritonavircontaining arm (Capsule Summary).

[Cohan 2014]

Virologic suppression rates were high at > 85% at all time points

and in both treatment arms throughout the trial. The randomized, controlled BAN trial conducted in Lilongwe,
Malawi also provides informative data on the role of antiretroviral therapy in preventing HIV transmission during
breastfeeding. In this study, 2369 HIV-infected breastfeeding mother-infant pairs (mothers required to have
3

CD4+ cell count 250 cells/mm ) were randomized to 1 of the following 28-week regimens: maternal triple
antiretroviral therapy (n = 849); daily infant nevirapine (n = 852); or no extended postnatal antiretroviral
regimen (n = 668).

[Chasela 2010]

The estimated HIV transmission risk between postnatal Weeks 2-28 was

significantly higher, at 5.7%, for infants in the group that received no extended postnatal antiretroviral therapy
than for infants in the maternal-regimen group (2.9%; P = .009) or for those in the infant-regimen group
(1.7%; P < .001). The results demonstrated that either maternal triple antiretroviral therapy or
infant nevirapine was effective at reducing the risk of HIV transmission during breastfeeding.

Premastication of food has also been associated with HIV transmission and should be avoided. Women should
be counseled regarding contraceptive choices. A dual protection strategy may be considered to protect against
both unintended pregnancy and HIV transmission in the postpartum period.

Keywords: Pregnancy, Women

Mode of Delivery
SUMMARY

Women whose HIV-1 RNA remains > 1000 copies/mL near the time of delivery should be advised to
undergo Cesarean section(Management Guidelines)

[DHHS Perinatal]

It is unclear if scheduled Cesarean section delivery would provide additional reduction in perinatal
transmission risk for women receiving antiretroviral therapy with HIV-1 RNA 1000 copies/mL

Invasive fetal monitoring, operative delivery with vacuum devices or forceps, and artificial or
prolonged rupture of membranes should be avoided in HIV-infected women

[Mofenson 1999; Shapiro 1999]

Women whose HIV-1 RNA remains > 1000 copies/mL should be recommended to undergo Cesarean section,
whereas it is unclear if Cesarean section delivery confers added benefit in women receiving antiretroviral
therapy with plasma HIV-1 RNA 1000 copies/mL(Management Guidelines).

[DHHS Perinatal]

In women with HIV-1

RNA > 1000 copies/mL, a Cesarean section should be scheduled at 38 weeks of gestation, if possible.
Intravenous zidovudine should be used, with infusion initiated 3 hours before the scheduled Cesarean section
delivery (2 mg/kg over 1-hour loading dose, then 1 mg/kg/hour continuous infusion until delivery, ie, umbilical
cord ligated).
In women whose HIV-1 RNA is 1000 copies/mL, Cesarean section delivery required for standard obstetric
indications should be performed at 39 weeks of gestation. Invasive fetal monitoring or operative delivery with
vacuum devices or forceps should be avoided in HIV-infected women, as these may increase risk of
transmission.

[Mofenson 1999; Shapiro 1999]

Likewise, artificial or prolonged rupture of membranes should be avoided,

and women should be moved toward Cesarean section delivery if labor does not progress 4 hours after
membranes have ruptured (C). Intravenous infusion with zidovudine should be initiated at the onset of labor,
using the dosing schedule outlined for Cesarean section.

Keywords: Drug-Drug Interactions, Pregnancy, Switch Strategies, Women

Concurrent Antiretroviral Therapy and


Other Medications
SUMMARY

Women should continue their oral ART regimen as prescribed before and during labor and
delivery (Management Guidelines)

[DHHS Perinatal]

Intravenous zidovudine infusion should replace oral zidovudine

Methylergonovine should be avoided in women receiving PIs or efavirenz

HIV-infected women who present to labor and delivery who are not receiving ART, or women who

[DHHS Perinatal]

have a positive rapid HIV test at labor and delivery, should initiate IV zidovudine as soon as possible
and undergo Cesarean section delivery

[DHHS Perinatal]

Women should continue their oral antiretroviral therapy regimen as prescribed before and during the
[DHHS Perinatal]

labor/delivery process (Management Guidelines).

The intravenous zidovudine infusion should

replace oral zidovudine. Therefore, women receiving a fixed-dose combination pill


of lamivudine/zidovudine should receive lamivudine 150 mg every 12 hours rather than
the lamivudine/zidovudinecombination pill formulation. Additional antiretroviral agents should be administered
as prescribed with the exception of stavudine.Zidovudine and stavudine are antagonistic and, therefore, should
not be used concurrently. Methylergonovine should be avoided in women receiving PIs or efavirenz because of
the risk of exaggerated vasoconstrictive responses. If absolutely required, the lowest possible dose
ofmethylergonovine should be used.

Additional considerations should be taken in the following scenarios.

Women who present to labor and delivery who are not receiving antiretroviral therapy:

Intravenous zidovudine infusion (2 mg/kg loading dose followed by 1 mg/kg/hour continuous infusion) should
be initiated as soon as possible

Women should undergo Cesarean section delivery

Infants should receive zidovudine for 6 weeks unless testing confirms positivity

Infants of mothers with suboptimal viral suppression may also receive a full antiretroviral therapy regimen

Women who have positive rapid HIV testing at labor and delivery:

Intravenous zidovudine infusion (2 mg/kg loading dose followed by 1 mg/kg/hour continuous infusion) should
be initiated as soon as possible

Women should undergo Cesarean section delivery

Confirmation testing should be completed after delivery

Infants should receive zidovudine until the mothers HIV status is confirmed and infant test results are
confirmed

Keywords: Drug-Drug Interactions, Pregnancy, Switch Strategies, Women

Postpartum Management
SUMMARY

Continuation of ART postpartum is recommended unless a contraindication exists (Management


Guidelines)

[DHHS Perinatal]

However, decisions regarding ART continuation postpartum should be made with


consultation between the woman and her HIV provider, preferably before delivery

ART may be simplified to increase adherence

Breastfeeding is currently not recommended in any HIV-infected women with access to clean water
and formula, regardless of HIV-1 RNA level

[DHHS Perinatal]

Current recommendations highlight the need for antiretroviral therapy for all HIV-infected patients, because
untreated HIV infection or uncontrolled viremia may be associated with adverse outcomes including increased
risk of cardiovascular disease, liver disease, and neurologic complications (Management Guidelines).
ART]

[DHHS

Moreover, the SMART study demonstrated that among patients with a prior CD4+ cell count < 350
3

cells/mm , interrupting antiretroviral therapy is associated with an increased risk of immunologic impairment
resulting in risk of opportunistic disease or death from any causeas well as a higher risk of AIDS-defining
[El-Sadr 2006;Lundgren 2008; Silverberg 2007]

malignancies.

Therefore, there is no longer a solid rationale to stop

antiretroviral therapy in the postpartum period. However, decisions regarding the continuation of antiretroviral
therapy postpartum should involve consultation between the woman and her HIV provider, preferably before
delivery, and with the following considerations in mind (Management Guidelines)

[DHHS Perinatal]

The option of continuing antiretroviral therapy in women who initiated antiretroviral therapy for fetal protection
should be recommended unless a contraindication exists; however, antiretroviral therapy may be simplified to
increase adherence

Women who received an NNRTI (nevirapine or efavirenz) and elect to discontinue antiretroviral therapy after
delivery should discontinue the NNRTI while continuing the other antiretroviral agents (NRTIs) for an additional
week to decrease the risk of NNRTI resistance. Alternatively, a PI may be substituted for the NNRTI for 7 days
and then all antiretroviral therapy discontinued simultaneously. Women whose antepartum regimen did not
include an NNRTI and who plan to discontinue antiretroviral therapy after delivery can stop all drugs
simultaneously

Adherence to antiretroviral therapy should be reinforced postpartum as it often decreases during this period;
clinicians should evaluate patients for issues that may reduce adherence (eg, depression or drug and alcohol
use)

Breastfeeding is not recommended in any HIV-infected women with access to clean water and formula,
regardless of HIV-1 RNA level, because of the increased risk of HIV transmission (C).

[DHHS Perinatal]

However, in

settings that lack such access and where breastfeeding is required for infant health, data from the PROMOTE
study comparing efavirenz plus lamivudine/zidovudine withlopinavir/ritonavir plus lamivudine/zidovudine in 389
pregnant women in rural Uganda are informative. Antiretroviral therapy was initiated at 12-28 weeks of
gestation and continued to 1 year or throughout breastfeeding (women were counseled to breastfeed for 1
year). A recent subanalysis of the study revealed a very low HIV transmission rate of 0.5% among live-born
infants, including only 1 case of transmission during breastfeeding, which occurred in the lopinavir/ritonavircontaining arm (Capsule Summary).

[Cohan 2014]

Virologic suppression rates were high at > 85% at all time points

and in both treatment arms throughout the trial. The randomized, controlled BAN trial conducted in Lilongwe,
Malawi also provides informative data on the role of antiretroviral therapy in preventing HIV transmission during
breastfeeding. In this study, 2369 HIV-infected breastfeeding mother-infant pairs (mothers required to have
3

CD4+ cell count 250 cells/mm ) were randomized to 1 of the following 28-week regimens: maternal triple
antiretroviral therapy (n = 849); daily infant nevirapine (n = 852); or no extended postnatal antiretroviral
regimen (n = 668).

[Chasela 2010]

The estimated HIV transmission risk between postnatal Weeks 2-28 was

significantly higher, at 5.7%, for infants in the group that received no extended postnatal antiretroviral therapy
than for infants in the maternal-regimen group (2.9%; P = .009) or for those in the infant-regimen group
(1.7%; P < .001). The results demonstrated that either maternal triple antiretroviral therapy or
infant nevirapine was effective at reducing the risk of HIV transmission during breastfeeding.

Premastication of food has also been associated with HIV transmission and should be avoided. Women should
be counseled regarding contraceptive choices. A dual protection strategy may be considered to protect against
both unintended pregnancy and HIV transmission in the postpartum period.

Keywords: Pregnancy, Women

Care of Menopausal HIV-Infected Women


SUMMARY

HIV-infected women may be at increased risk for conditions linked with estrogen deficiency

[Kanapathipillai

2013; Cejtin 2012;Coutinho 2013; Karim 2013]

Age of Menopause

Lower CD4+ cell count, low physical activity, and injection drug use may be associated with
earlier menopause in HIV-infected women

[Schoenbaum 2005]

Symptoms of Menopause

Severity of menopause symptoms may be altered in HIV-infected women

[Fantry 2005; Zablotsky

2003; Kanapathipillai 2013]

Treatment of Menopause Symptoms

Current evidence supports the use of hormone replacement therapy for relief of vasomotor
symptoms associated with menopause, although data in HIV-infected women are lacking

Potential drug interactions between hormone replacement therapy and ART are not known

Additional Considerations for HIV-Infected Postmenopausal Women

Postmenopausal women should undergo routine health screening, including annual Pap
smears and screening for STDs, breast cancer, colon cancer, osteoporosis, cardiovascular
risks, and depression

[Kojic 2007]

By 2015, more than one half of all HIV-infected individuals in the United States will be older than 50 years of
age because of the success of antiretroviral therapy. Currently, approximately 30% of women with HIV are 50
years of age or older.

[CDC 2012; CDC 2013b]

Therefore, more HIV-infected women are undergoing the menopause

transition. Menopause is defined as the permanent cessation of menstruation caused by the loss of ovarian
function and is clinically measured as the absence of menses for 12 months in the absence of other etiologies.
Biochemically, menopause is associated with a persistently elevated follicle stimulating hormone level and
diminished estradiol level. Certain medical conditions, such as osteoporosis and cardiovascular disease, have
been linked with estrogen deficiency. HIV-infected women may be at increased risk for these conditions as
well.
2013]

[Kanapathipillai 2013; Cejtin 2012]

For example, one study suggested that vascular elasticity is lower in women,

[Coutinho

and decreased estrogen and androgen levels in HIV-infected women may exacerbate atrial stiffness

compared with HIV-negative women.

[Karim 2013]

Therefore, understanding if and when an HIV-infected woman

undergoes transition to menopause is important. Of note, symptoms associated with menopause are also
commonly associated with HIV infection itself.

For additional information from inPractice on issues related to aging in HIV-infected patients, click here.

Age of Menopause
Earlier age of menopause has been associated with increased risk for medical diseases and increased
mortality. Although the overall median age of menopause in the United States is 51.4 years,
conflicting data as to whether HIV infection is associated with an earlier onset.

[Imai 2013]

[Gold 2001]

there are

Smoking, injection drug

use, black race, and lower education level have been associated with an earlier onset of menopause in the
general population.

[Bromberger 1997; Kanapathipillai 2013]

Lower CD4+ cell count, low physical activity, and injection drug

use may be associated with earlier menopause in HIV-infected women.

[Schoenbaum 2005; Kanapathipillai 2013]

Symptoms of Menopause
The symptoms associated with menopause appear to be similar in HIV-positive and HIV-negative women.
However, the severity of symptoms may be altered.

[Fantry 2005; Kanapathipillai 2013]

HIV-infected black women may

have more vasomotor symptoms. More severe immunosuppression is associated with diminished vasomotor
symptoms. Women with depressive symptoms, reports of negative life events, and those receiving public
assistance report higher rates of menopausal symptoms. Irritability, depression, emotional liability, and
reduced concentration may be 25% to 50% more prevalent in HIV-infected women.

[Zablotsky 2003]

Treatment of Menopause Symptoms


Current evidence supports the use of hormone replacement therapy for relief of menopausal symptoms,
especially the vasomotor effects. However, there are no available data demonstrating safety in the HIV
population. Whether or not there is a drugdrug interaction between hormone replacement therapy and
antiretroviral therapy is unknown.

Additional Considerations for HIV-Infected Postmenopausal Women


Postmenopausal women should continue to undergo routine health screening which can include

Annual Pap smears

Sexually transmitted infection screening

Syphilis

Gonorrhea/chlamydia

Breast cancer screening

Colon cancer screening

Osteoporosis screening and prevention

Women should be encouraged to perform weight-bearing exercises regularly

1000-1500 mg/day of calcium with 400 IU/day vitamin D

Annual dual energy x-ray absorptiometry screening

Cardiovascular risk screening

Depression screening

[Kojic 2007]

The importance of screening older adult populations for sexually transmitted diseases may be
underappreciated. However, factors that could increase the risk of acquiring a sexually transmitted disease
among older adults include the loss of a spouse

[Smith 2009]

protection among older vs younger sexual risk takers.

as well as reduced likelihood of using barrier

[Stall 1994]

Therefore, it is important that older women as

well as men are routinely screened for sexually transmitted diseases, particularly after acquiring a new sexual
partner.

For additional information from inPractice on the aging HIV population, click here.

Keywords: Endocrine Disorders, HIV and Older Patients, Women

Primary Care Essentials


SUMMARY

Because primary care physicians will provide an increasing amount of care for HIV-infected women
over time, they will need to become more knowledgeable of critical management considerations when
treating HIV-infected women and more comfortable determining when specialty consultation is
needed

Routine clinical care for HIV-infected women should include immunizations, cardiovascular disease
risk assessment, psychosocial assessment, and screening for tuberculosis, breast cancer,
depression, STDs, cervical cancer, and anal cancer

The US Department of Health and Human Services adult antiretroviral therapy guidelines recommend
that all HIV-infected persons initiate antiretroviral therapy regardless of CD4+ cell count to prevent
sexual transmission of HIV in addition to preventing disease progression in the
individual (Management Guidelines)

[DHHS ART]

Factors that should be considered when selecting an initial antiretroviral therapy regimen for women
infected with HIV include: childbearing potential and use of hormonal contraceptives, HIV serostatus
of partners, risk for adverse effects of antiretroviral agents, comorbidities, and anticipated
antiretroviral adherence

When counseling HIV-infected women on the use of safe and effective contraception, primary care
physicians can explain the importance of dual forms of contraception: barrier (condom) and hormonal
(or sterilization)

Pharmacokinetic interaction should be considered when oral contraceptives and antiretroviral agents
are used together and certain agents should not be used concurrently

The DHHS recommends use of antiretroviral therapy by all HIV-infected pregnant women to reduce
the risk of mother-to-child transmission of HIV regardless of CD4+ cell count (Management
Guidelines)

[DHHS Perinatal]

The US Centers for Disease Control and Prevention recommend routine prenatal HIV screening in the
first trimester for all pregnant women, with consideration of repeat testing in the third
trimester (Management Guidelines)

[CDC Testing 2006]

All postmenopausal women, including those with HIV infection, should undergo routine health
screening, including annual Pap smears and screening for STDs, breast cancer, colon cancer,
osteoporosis, cardiovascular risk factors, and depression.

[Kojic 2007]

Primary care physicians will provide an increasing amount of care for HIV-infected women. Increased
identification and early initiation of treatment of HIV infection with simpler and more potent antiretroviral therapy
has resulted in increased longevity and decreased mortality. Sex-specific issues such as pregnancy, breast
and cervical cancer screening and prevention, and menopause have become more important components of
the overall care of HIV-infected women. As such, HIV-infected women will rely less on specialized care and
more on primary care physicians. Therefore, primary care providers need to become more knowledgeable of
critical management considerations for this population and more comfortable determining when specialty
consultation is needed. In general, the management of HIV-infected women in the primary care setting shares
many similarities with the management of HIV-uninfected women but with some important differences. This
section of the module will highlight key aspects of care provision for HIV-infected women that should be
considered in the primary care setting.

Routine clinical care for HIV-infected women should include all of the following:

Immunizations: vaccine recommendations are generally similar between HIV-positive and HIV-negative
patients with the exclusion of live viral-based vaccines

Tuberculosis screening: screening for latent tuberculosis infection should be performed at the time of HIV
diagnosis and annually thereafter in HIV-infected women with an ongoing risk for tuberculosis acquisition (C)

Cardiovascular disease risk screening: HIV-infected patients should be screened for traditional modifiable risk
factors, including cigarette smoking, hypertension, hyperlipidemia, diabetes, and obesity, because HIV
infection itself may increase cardiovascular disease risk.

[Kaplan 2007; Freiberg 2013]

These factors should be

addressed at each physician visit with behavioral and pharmacologic interventions as appropriate

[Currier 2008]

Breast cancer screening: HIV-infected women should follow standard age-based recommendations for regular
mammograms and breast self-examinations established for all women, regardless of HIV status

Psychosocial assessment: psychosocial stressors should be evaluated on a regular basis in HIV-infected


women as these factors can negatively affect adherence to antiretroviral therapy and participation in clinical

care. A multidisciplinary team that incorporates social services, mental health, and case management is often
required to maintain ongoing clinical care and medication compliance in this population

[Cunningham 2008; Pillai 2009]

Depression screening: HIV-infected patients should receive ongoing screening for depression, with referral for
appropriate mental health intervention when indicated. This is especially important for HIV-infected women as
the rate of depressive symptoms or disorders in this population is nearly double that in HIV-infected men.
2001; Cook 2002a]

In addition, 1 in 5 HIV-infected women meet the classification for major depressive disorders

compared with 1 in 20 HIV-negative women.

[Morrison 2002]

Depression in HIV-infected women is associated with

several negative sequelae, including increased rates of all-cause and AIDS-related mortality,
2002b]
2007]

[Ickovics

potentially higher rates of sexually transmitted diseases (STDs) and substance abuse,

and decreased cognitive function.

[Fialho 2013]

[Cook

[Chander 2006; Berg

Additionally, depression has been linked to intimate partner

violence necessitating inquiry into safe partnerships and living environments.

STD screening: Sexually active women should receive routing screening for STDs, including for gonorrhea,
chlamydia, trichomonas, syphilis, bacterial vaginosis, vulvovaginal candidiasis, herpes simplex virus, and
human papillomavirus. STDs can facilitate HIV transmission by increasing genital shedding of HIV.
1997]

[Cohen

STD screening should also be conducted after a new HIV diagnosis, with a new sexual partner, following a

condom malfunction, after unprotected intercourse, or when there is a known exposure to an STD.

Cervical cancer screening: Cancer screening, including human papillomavirus testing and a Pap test, should
be conducted every 6 months in the first year after HIV diagnosis and annually thereafter, unlike HIV-negative
women who now require screening every 3 years.

[CDC Cervical Cancer Screening]

The increased frequency of screening

is due to the 4-5 times higher incidence of cervical intraepithelial neoplasia in HIV-positive women compared to
their HIV-negative peers.

[Wright 1994a; Wright 1994b; Ellerbrock 2000]

cytology results and human papillomavirus DNA.

Colposcopy should be offered based on cervical

[Cohn 2001; Goldie 2001; Harris 2005; Kitchener 2007]

Anal cancer screening: Anal cytologic screening is now being recommended for HIV-infected women, followed
by high-resolution anoscopy in women with abnormal cytologic results, regardless of history of receptive anal
intercourse.

[CDC OI]

The US Department of Health and Human Services adult antiretroviral therapy guidelines recommend that all
HIV-infected persons initiate antiretroviral therapy regardless of CD4+ cell count to prevent sexual
transmission of HIV in addition to preventing disease progression in the individual (Management
Guidelines).

[DHHS ART]

Factors that should be considered when selecting an initial antiretroviral therapy regimen

for women infected with HIV include childbearing potential and use of hormonal contraceptives, HIV serostatus
of partners, risk for adverse effects of antiretroviral agents, comorbidities, and anticipated antiretroviral
adherence. Despite recommendations for antiretroviral therapy initiation, considerable numbers of HIV-infected
women with clinical indications for treatment in the United States are not receiving antiretroviral therapy. In
addition, there are several notable differences between the course of antiretroviral therapy in HIV-infected
women vs that in HIV-infected men, including higher rates of treatment-associated adverse events

[Prins 2005; Molina

2010; Mills 2009; Brinkman 1999; Bersoff-Matcha 2001; Mazhude 2002; Sanne 2005]

discontinuation because of adverse events

[Lucas 1999]

and antiretroviral therapy modification or

in women vs men.

There are special considerations for reproductive health in HIV-infected women when compared with the
general population. These include issues related to contraception, pregnancy, and menopause. Women with
HIV infection often feel stigmatized by their diagnosis and, therefore, do not seek appropriate care, which can
be detrimental to all facets of reproductive health. Primary care physicians can play an important role in
addressing these issues by initiating discussions with HIV-infected women during routine primary care
appointments.

When counseling HIV-infected women on the use of safe and effective contraception, primary care physicians
can explain the importance of dual forms of contraception: barrier (condom) and hormonal (or sterilization).
Dual mechanisms are necessary because antiretroviral agents may alter the clinical effectiveness of many of
the available contraceptive choices, and contraceptive agents may alter the efficacy of some antiretroviral
agents. Additionally, barrier (condom) contraception is also important to reduce the risk of sexual transmission
of HIV to intimate partners. Virologic responses to antiretroviral therapy should be monitored closely when
used in combination with nonbarrier contraceptives. Pharmacokinetic interaction should be considered when
combined oral contraceptives and antiretrovirals are used together and certain agents should not be used
concurrently. Limited data exist regarding the use of implantable or intravaginal contraception in HIV-infected
women. However, the Centers for Disease Control and Preventions Medical Eligibility Criteria for
Contraceptive Use lists all combined hormonal contraceptive methods (including the patch and vaginal ring) as
Category 1 (no restriction for use) for women at high risk for HIV or with HIV or AIDS.

[CDC MEC]

Both the copper-

containing intrauterine device (Tcu-380A IUD) and the levonorgestrel-releasing intrauterine contraceptive
system are acceptable choices for HIV-infected women at low risk for acquiring STDs.

[DHHS ART]

The US Department of Health and Human Services recommends the use of antiretroviral therapy by all HIVinfected pregnant women to reduce the risk of mother-to-child transmission of HIV regardless of CD4+ cell
count (Management Guidelines).

[DHHS Perinatal]

In many cases, HIV infection may be initially diagnosed during

pregnancy. The Centers for Disease Control and Prevention recommend routine prenatal HIV screening in the
first trimester for all pregnant women, with consideration of repeat testing in the third trimester (Management
Guidelines)

[CDC Testing 2006]

In addition, women who present to labor and delivery with unknown HIV status or

who are at risk for HIV acquisition should undergo rapid HIV testing. If the results of the rapid test are positive
or unknown, intravenous zidovudine should be administered without waiting for confirmation of HIV status.
Primary care physicians should involve both obstetrical providers and HIV specialists in the medical care of
HIV-infected pregnant women throughout the entire gestational period especially regarding selection
ofappropriate antiretroviral therapy, management of prenatal care and delivery, and treatment of HIV-exposed

infants. Key management strategies for HIV-infected pregnant women include the following (Management
Guidelines)

[DHHS Perinatal]

HIV-infected pregnant women should follow the same vaccination schedule as nonpregnant HIV-infected
individuals, with particular attention to the need for hepatitis A and B vaccination (if antibodies are not present)
and influenza virus vaccine, inactivated

HIV-infected pregnant women should be monitored with greater frequency for antiretroviral treatment response
and complications

Intravenous zidovudine administered near delivery is recommended for HIV-infected pregnant women with
HIV-1 RNA > 1000 copies/mL or unknown HIV-1 RNA levels unless there is evidence of resistance or toxicity

Women whose HIV-1 RNA remains > 1000 copies/mL near the time of delivery should be advised to
undergo Cesarean section

Women should continue their oral antiretroviral therapy regimen as prescribed before and during labor and
delivery

Antiretroviral therapy should be continued postpartum unless a contraindication exists

However, decisions regarding antiretroviral therapy continuation postpartum should be made with consultation
between the woman and her HIV provider, preferably before delivery

Breastfeeding is currently not recommended in any HIV-infected women with access to clean water and
formula, regardless of HIV-1 RNA level

Based on the success of antiretroviral therapy, the proportion of HIV-infected women who are 50 years of age
or older continues to increase, with a concomitant increase in the need for effective management of
menopausal symptoms in this group. All postmenopausal women, including those with HIV infection, should
undergo routine health screening, including annual Pap smears and screening for STDs, breast cancer, colon
cancer, osteoporosis, cardiovascular risk factors, and depression.

[Kojic 2007]

Evidence suggests that several

important interactions may occur between HIV infection and menopause, and primary care physicians may be
better able to assist HIV-infected women experiencing complications of menopause if they have an
understanding of this potential interplay. Several potential associations that may be useful to consider include

Earlier menopause in HIV-infected women may be associated with lower CD4+ cell count, low physical activity,
and injection drug use

[Schoenbaum 2005]

HIV-infected women may be at increased risk for conditions linked with estrogen deficiency

[Kanapathipillai 2013; Cejtin

2012; Coutinho 2013; Karim 2013]

Severity of menopause symptoms may be altered in HIV-infected women

[Fantry 2005; Zablotsky 2003]

Current evidence supports the use of hormone replacement therapy for relief of menopausal symptoms,
especially the vasomotor effects. However, there are no available data demonstrating safety in the HIV
population. Whether or not there are drugdrug interactions between hormone replacement therapy and
antiretroviral therapy is unknown.

Keywords: Primary Care Considerations, Women

DR. CARLOS RODOLFO MEJIA VILLATORO

MY SUBSCRIPTIONS

QUICK TOUR

MY CE

MY FOLDER

LOGOUT

Specialty

Decision Tools

Drug Reference

Guidelines

XGO

PubMed

Trials

More

Specialty

HIV

Management of Specific Populations

HIV-Infected Women

Summary

Introduction

Primary Care of HIV-Infected Women

Immunizations

Screening and Risk Factors

Reproductive Health Considerations

Oral Contraceptives

Injectable Contraceptives

Implantable, Intravaginal, and Intrauterine Contraceptives

Barrier Contraceptives

STDs

Cervical Cancer Screening

Antiretroviral Therapy

Treatment Initiation

Treatment Outcomes

Treatment Complications

Depression and HIV-Infected Women

Effect of Depression on ART and Outcomes

Treatment of Depression

Care of Pregnant HIV-Infected Women

HIV Screening in Pregnant Women

Initial Evaluation

ART During Pregnancy

Monitoring During Pregnancy

Immunizations

Intrapartum Management

Mode of Delivery

Concurrent ART and Other Medications

Postpartum Management

Care of Menopausal HIV-Infected Women

Age of Menopause

Symptoms of Menopause

Treatment of Menopause Symptoms

Additional Considerations

Primary Care Essentials

Supporting Assets

References

Jointly Sponsored by inPractice Resources, LLC, and:

more information about our sponsors

Save

Share

Print

Email

Previous

Special Considerations in the Management of HIV-Infected Women, Including


Management of Conception and Pregnancy

Author: Kristine Patterson, MD (More Info)

Section Editor: Judith S. Currier, MD, MSc

Editors in Chief: Joseph J. Eron, Jr., MD; Daniel R. Kuritzkes,


MD; Kathleen E. Squires, MD

Last Reviewed: 4/24/14 (What's New)

References
Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA. Primary care guidelines for the
management of persons infected with HIV: 2013 update by the HIV Medicine Association of the Infectious
Diseases Society of America. Clin Infect Dis. 2014;58:1-10.[Aberg 2014]
Abraham AG, DSouza G, Jing Y, et al. Invasive cervical cancer risk among HIV-infected women: a North
American multicohort collaboration prospective study. J Acquir Immune Defic Syndr. 2013;62:405413.[Abraham 2013]

Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol
to Reduce Atherosclerotic Cardiovascular Risk in Adults: a report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;[Epub ahead of
print].[ACC/AHA Cholesterol]

ACIP Adult Immunization Work Group, Bridges CB, Coyne-Beasley T, et al. Advisory Committee on
Immunization Practices (ACIP) recommended immunization schedule for adults aged 19 years and older
United States, 2014. MMWR Surveill Summ. 2014;63:110-112.[ACIP Schedule]

The American College of Obstetricians and Gynecologists. Gynecologic care for women with human
immunodeficiency virus. Practice bulletin. Number 117. December 2010;116:1492-1509.[ACOG 2010]

American Cancer Society guidelines for breast cancer screening: update 2003. Available at:
http://www.cancer.org/healthy/findcancerearly/cancerscreeningguidelines/american-cancer-society-guidelinesfor-the-early-detection-of-cancer. Accessed April 11, 2014.[ACS 2003]

Alciati A, Gallo L, Monforte AD, Brambilla F, Mellado C. Major depression-related immunological changes and
combination antiretroviral therapy in HIV-seropositive patients. Hum Psychopharmacol. 2007;22:33-40.[Alciati
2007]

Althoff KN, Rebeiro P, Brooks JT, et al. Disparities in the quality of HIV care when using US Department of
Health and Human Services indicators. Clin Infect Dis. 2014;[Epub ahead of print].[Althoff 2014]

Anastos K, Gange SJ, Lau B, et al. Association of race and gender with HIV-1 RNA levels and immunologic
regression. J Acquir Immune Defic Syndr. 2000;24:218-226.[Anastos 2000]

Anastos K, Schneider MF, Gange SJ, et al. The association of race, sociodemographic, and behavioral
characteristics with response to highly active antiretroviral therapy in women. J Acquir Immune Defic Syndr.
2005;39:537-544.[Anastos 2005]

Anderson MS, Hanley WD, Moreau AR, et al. Effect of raltegravir on estradiol and norgestimate plasma
pharmacokinetics following oral contraceptive administration in healthy women. Br J Clin Pharmacol.
2011;71:616-620.[Anderson 2011]

Andrade A, Baheti G, Smeaton L, et al. Sex and geographic differences in atazanavir pharmacokinetics in
subjects treated with didanosine, emtricitabine and atazanavir in the ACTG PEARLS study. Program and
abstracts of the 18th Conference on Retroviruses and Opportunistic Infections; February 27 - March 2, 2011;
Boston, Massachusetts. Abstract 648.[Andrade 2011]

Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral pregnancy registry internation interim
report for 1 January 1989 through 31 July 2013. Available at :
http://www.apregistry.com/forms/interim_report.pdf. Accessed April 11, 2014.[APRSC 2013]

Atashili J, Poole C, Ndumbe PM, Admiora AA, Smith JS. Bacterial vaginosis and HIV acquisition: a metaanalysis of published studies. AIDS. 2008;22: 1493-1501.[Atashili 2008]

Atrio J, Stanczyk FZ, Neely M, Cherala G, Kovacs A, Mishell DR Jr. Effect of protease inhibitors on steadystate pharmacokinetics of oral norethindrone contraception in HIV-infected women. J Acquir Immune Defic
Syndr. 2014;65:72-77.[Atrio 2014]

Belhadj H, Rasanathan JJ, Denny L, Broutet N. Sexual and reproductive health and HIV services: integrating
HIV/AIDS and cervical cancer prevention and control. Int J Gynaecol Obstet. 2013;121(suppl 1):S29S34.[Belhadj 2013]

Benson C, Hua L, Andersen J, et al. ZOSTAVAX is generally safe and immunogenic in HIV+ adults
virologically suppressed on ART: results of a phase 2, randomized, double-blind, placebo-controlled trial.
Program and abstracts of the 19th Conference on Retroviruses and Opportunistic Infections; March 5-8, 2012;
Seattle, Washington. Abstract 96.[Benson 2012]

Berg CJ, Michelson SE, Safren SA. Behavioral aspects of HIV care: adherence, depression, substance use,
and HIV-transmission behaviors. Infect Dis Clin North Am. 2007;21:181-200.[Berg 2007]

Bersoff-Matcha SJ, Miller WC, Aberg JA, et al. Sex differences in nevirapine rash. Clin Infect Dis. 2001;32:124129.[Bersoff-Matcha 2001]

Brinkman K, Smeitink JA, Romijn JA, Reiss P. Mitochondrial toxicity induced by nucleoside-analogue reversetranscriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy.
Lancet. 1999;354:1112-1115.[Brinkman 1999]

Brogly SB, Abzug MJ, Watts DH, et al. Birth defects among children born to human immunodeficiency virusinfected women: pediatric AIDS clinical trials protocols 219 and 219C. Pediatr Infect Dis J. 2010;29:721727.[Brogly 2010]

Bromberger JT, Matthews KA, Kuller LH, Wing RR, Meilahn EN, Plantinga P. Prospective study of the
determinants of age at menopause. Am J Epidemiol. 1997;145:124-133.[Bromberger 1997]

Bulterys M, Landesman S, Burns DN, Rubinstein A, Goedert JJ. Sexual behavior and injection drug use during
pregnancy and vertical transmission of HIV-1. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;15:7682.[Bulterys 1997]

Burns DN, Landesman S, Muenz LR, et al. Cigarette smoking, premature rupture of membranes, and vertical
transmission of HIV-1 among women with low CD4+ levels. J Acquir Immune Defic Syndr. 1994;7:718726.[Burns 1994]

Campbell T, Smeaton L, De Grutolla V, et al. PEARLS (ACTG A5175): a multinational study of didanosine-EC,
emtricitabine and atazanavir vs co-formulated zidovudine/lamivudine and efavirenz for initial treatment of HIV-1
infection. Program and abstracts of the 17th International AIDS Conference; August 3-8, 2008; Mexico City,
Mexico. Abstract THAB0404.[Campbell 2008]

Campbell TB, Smeaton LM, Kumarasamy N, et al. Efficacy and safety of three antiretroviral regimens for initial
treatment of HIV-1: a randomized clinical trial in diverse multinational settings. PLoS Med.
2012;9:e1001290.[Campbell 2012]

Castilho JL, Melekhin VV, Sterling TR. Sex differences in HIV outcomes in the highly active antiretroviral
therapy era: a systematic review. AIDS Res Hum Retroviruses. 2014;30:446-456.[Castilho 2014]

Centers for Disease Control and Prevention. HIV/AIDS surveillance report, 2009; vol. 21. Published February
2011. Available at: http://www.cdc.gov/hiv/surveillance/resources/reports/2009report/. Accessed September
24, 2012.[CDC 2011]

Centers for Disease Control and Prevention. HIV Surveillance Report, 2010; vol. 22. March 2012. Available at:
http://www.cdc.gov/hiv/topics/surveillance/resources/reports/. Accessed April 11, 2014.[CDC 2012]

Centers for Disease Control and Prevention. Monitoring selected national HIV prevention and care objectives
by using HIV surveillance dataUnited States and 6 US dependent areas2011. HIV Surveillance
Supplemental Report 2013;18(No. 5). October 2013. Available at:
http://www.cdc.gov/hiv/topics/surveillance/resources/reports/. Accessed April 11, 2014.[CDC 2013a]

Centers for Disease Control and Prevention. Diagnoses of HIV infection among adults aged 50 years and older
in the United States and dependent areas, 2007-2010. HIV Surveillance Supplemental Report 2013;18(No. 3).
February 2013. Available at: http://www.cdc.gov/hiv/topics/surveillance/resources/reports/#supplemental.
Accessed April 11, 2014.[CDC 2013b]

US Centers for Disease Control and Prevention. Cervical cancer screening guidelines for average-risk women.
Available at: http://www.cdc.gov/cancer/cervical/pdf/guidelines.pdf. Accessed April 22, 2014.[CDC Cervical
Cancer Screening]

Centers for Disease Control and Prevention. Update to CDC's U.S. Medical Eligibility Criteria for Contraceptive
Use, 2010: revised recommendations for the use of hormonal contraception among women at high risk for HIV
infection or infected with HIV. MMWR Morb Mortal Wkly Rep. 2012;61:449-452.[CDC MEC]

Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and
treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the
Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine
Association of the Infectious Diseases Society of America. Available at:
http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed April 11, 2014.[CDC OI]

Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010.
Available at: http://www.cdc.gov/std/treatment/2010/STD-Treatment-2010-RR5912.pdf. Accessed April 11,
2014.[CDC STD 2010]

Centers for Disease Control and Prevention. Revised recommendations for HIV testing of adults, adolescents,
and pregnant women in health-care settings. September 22, 2006. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5514a1.htm. Accessed April 11, 2014.[CDC Testing 2006]

Cejtin HE, Jacobson L, Springer G, et al. Effect of hormonal contraceptive use on plasma HIV-1-RNA levels
among HIV-infected women. AIDS. 2003;17:1702-1704.[Cejtin 2003]

Cejtin HE. Care of the human immunodeficiency virus-infected menopausal woman. Am J Obstet Gynecol.
2012 Aug;207(2):87-93. doi: 10.1016/j.ajog.2011.12.031. Epub 2011 Dec 30.[Cejtin 2012]

Cescon A, Patterson S, Chan K, et al. Gender differences in clinical outcomes among HIV-positive individuals
on antiretroviral therapy in Canada: a multisite cohort study. PLoS One. 2013;8:e83649.[Cescon 2013]

Cespedes MS, Aberg JA. Neuropsychiatric complications of antiretroviral therapy. Drug Saf. 2006;29:865874.[Cespedes 2006]

Chander G, Himelhoch S, Moore RD. Substance abuse and psychiatric disorders in HIV-positive patients:
epidemiology and impact on antiretroviral therapy. Drugs. 2006;66:769-789.[Chander 2006]

Chasela CS, Hudgens MG, Jamieson DJ, et al. Maternal or infant antiretroviral drugs to reduce HIV-1
transmission. N Engl J Med. 2010;362:2271-2281.[Chasela 2010]

Chew K, Bhattacharya D, McGinnis K, et al. Coronary heart disease risk by Framingham risk score in hepatitis
C virus and HIV/hepatitis C virus. Program and abstracts of the 20th Conference on Retroviruses and
Opportunistic Infections. March 3-6, 2013. Atlanta, Georgia. Abstract 716.[Chew 2013]

Chu JH, Gange SJ, Anastos K, et al. Hormonal contraceptive use and the effectiveness of highly active
antiretroviral therapy. Am J Epidemiol. 2005;161:881-890.[Chu 2005]

Clifford DB, Evans S, Yang Y, et al. Impact of efavirenz on neuropsychological performance and symptoms in
HIV-infected individuals. Ann Intern Med. 2005;143:714-721.[Clifford 2005]

Cohan D, Natureeba P, Plenty A, et al. Efficacy and safety of LPV/r versus EFV in HIV+ pregnant and breastfeeding Ugandan women. Program and abstracts of the 21st Conference on Retroviruses and Opportunistic
Infections; March 3-6, 2014; Boston, Massachusetts. Abstract 69.[Cohan 2014]

Cohen MS, Hoffman IF, Royce RA, et al. Reduction of concentration of HIV-1 in semen after treatment of
urethritis: implications for prevention of sexual transmission of HIV-1. Lancet. 1997;349:1868-1873.[Cohen
1997]

Cohen MS. Sexually transmitted diseases enhance HIV transmission: no longer a hypothesis. Lancet.
1998;351(suppl 3):5-7.[Cohen 1998]

Cohn JA, Gagnon S, Spence MR, et al. The role of human papillomavirus deoxyribonucleic acid assay and
repeated cervical cytologic examination in the detection of cervical intraepithelial neoplasia among human
immunodeficiency virus-infected women. Am J Obstet Gynecol. 2001;184:322-330.[Cohn 2001]

Cohn SE, Park JG, Watts DH, et al. Depo-medroxyprogesterone in women on antiretroviral therapy: effective
contraception and lack of clinically significant interactions. Clin Pharmacol Ther. 2007;81:222-227.[Cohn 2007]

Colebunders R, Hilbrands R, DeRoo A, et al. Neuropsychiatric reaction with abacavir. Am J Med.


2002;113:616.[Colebunders 2002]

Collazos J, Asensi V, Cartn JA. Sex differences in the clinical, immunological and virological parameters of
HIV-infected patients treated with HAART. AIDS. 2007;21:835-843.[Collazos 2007]

Colombo S, Buclin T, Cavassini M, et al. Population pharmacokinetics of atazanavir inpatients with human
immunodeficiency virus infection. Antimicrob Agents Chemother. 2006;50:3801-3808.[Colombo 2006]

Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human
immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076
Study Group. N Eng J Med. 1994;331:1173-1180.[Connor 1994]

Cook JA, Cohen MH, Burke J, et al. Effects of depressive symptoms and mental health quality of life on use of
highly active antiretroviral therapy among HIV-seropositive women. J Acquir Immune Defic Syndr.
2002;30:401-409.[Cook 2002a]

Cook JA, Cohen MH, Grey D, et al. Use of highly active antiretroviral therapy in a cohort of HIV-seropositive
women. Am J Public Health. 2002;92:82-87.[Cook 2002b]

Cook JA, Grey D, Burke-Miller J, et al. Effects of treated and untreated depressive symptoms on highly active
antiretroviral therapy use in a US multi-site cohort of HIV-positive women. AIDS Care. 2006;18:93-100.[Cook
2006]

Coutinho T, Borlaug BA, Pellikka PA, et al. Sex differences in arterial stiffness and ventricular-arterial
interactions. J Am Coll Cardiol. 2013 Jan 8;61(1):96-103. doi: 10.1016/j.jacc.2012.08.997. Epub 2012 Nov
1.[Coutinho 2013]

Crauwels H, van Heeswijk R, Cornelis L, et al. Pharmacokinetic interaction study between TMC278, an NNRTI,
and the contraceptives norethindrone plus ethinylestradiol. Program and abstract of the 12th European AIDS
Conference; November 11-14, 2009; Cologne, Germany. Abstract PE4.3/3[Crauwels 2009]

Cruess DG, Douglas SD, Petitto JM, et al. Association of resolution of major depression with increased natural
killer cell activity among HIV-seropositive women. Am J Psychiatry. 2005;162: 2125-2130.[Cruess 2005]

Cunningham WE, Wong M, Hays RD. Case management and health-related quality of life outcomes in a
national sample of persons with HIV/AIDS. J Natl Med Assoc. 2008;100:840-847.[Cunningham 2008]

Currier JS, Spino C, Grimes J, et al. Differences between women and men in adverse events and CD4+
responses to nucleoside analogue therapy for HIV infection. J Acquir Immune Defic Syndr. 2000;24:316324.[Currier 2000]

Currier JS, Lundgren JD, Carr A, et al. Epidemiological evidence for cardiovascular disease in HIV-infected
patients and relationship to highly active antiretroviral therapy. Circulation. 2008;118:e29-e35.[Currier 2008]

Currier J, Averitt Bridge D, Hagins D, et al. Sex-based outcomes of darunavir-ritonavir therapy: a single-group
trial. Ann Intern Med. 2010;153:349-357.[Currier 2010]

Daar ES, Tierney C, Fischl MA, et al. Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for
initial treatment of HIV-1. Ann Intern Med. 2011;154:445-456.[Daar 2011]

Dale S, Cohen M, Weber K, Cruise R, Kelso G, Brody L. Abuse and resilience in relation to HAART medication
adherence and HIV viral load among women with HIV in the United States. AIDS Patient Care STDS.
2014;28:136-143.[Dale 2014]

Denslow SA, Rositch AF, Firnhaber C, Ting J, Smith JS. Incidence and progression of cervical lesions in
women with HIV: a systematic global review. Int J STD AIDS. 2014;25:163-177.[Denslow 2014]

US Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1-infected
adults and adolescents. May 1, 2014. Available at:
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed May 19, 2014.[DHHS
ART]

US Department of Health and Human Services. Safety and toxicity of individual antiretroviral agents in
pregnancy. July 21, 2012. Available at: http://aidsinfo.nih.gov/guidelines/html/3/perinatalguidelines/190/appendix-a-supplement-safety-and-toxicity-of-individual-antiretroviral-agents-in-pregnancy.
Accessed April 11, 2014.[DHHS ARV Safety]

US Department of Health and Human Services Perinatal HIV Guidelines Working Group. Public Health Service
Task Force recommendations for use of antiretroviral drugs in pregnant HIV-infected women for maternal
health and interventions to reduce perinatal HIV transmission in the United States. March 28, 2014. Available
at: http://aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf. Accessed April 11, 2014.[DHHS Perinatal]

US Department of Health and Human Services. A guide to the clinical care of women with HIV. Available at:
http://hab.hrsa.gov/deliverhivaidscare/files/womenwithaids.pdf. Accessed April 11, 2014.[DHHS Women]

Dube MP, Lipshultz SE, Fichtenbaum CJ, Greenberg R, Schecter AD, Fisher SD. Effects of HIV infection and
antiretroviral therapy on the heart and vasculature. Circulation. 2008,118:e36-e40.[Dube 2008]

Sustiva [package insert]. Princeton, NJ: Bristol-Myers Squibb; May 2013.[Efavirenz PI]

El-Ibiary SY, Cocohoba JM. Effects of HIV antiretrovirals on the pharmacokinetics of hormonal contraceptives.
Eur J Contracept Reprod Health Care. 2008;13:123-132.[El-Ibiary 2008]

El-Sadr WM, Lundgren JD, Neaton JD, et al; Strategies for Management of Antiretroviral Therapy (SMART)
Study Group. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:22832296.[El-Sadr 2006]

Ellerbrock TV, Chiasson MA, Bush TJ, et al. Incidence of cervical squamous intraepithelial lesions in HIVinfected women. JAMA. 2000;283:1031-1037.[Ellerbrock 2000]

Stribild [package insert]. Foster City, CA: Gilead Sciences; October 2013.[ELV/COBI/TDF/FTC PI]

Evans DL, Ten Have TR, Douglas SD, et al. Association of depression with viral load, CD8 T lymphocytes, and
natural killer cells in women with HIV infection. Am J Psychiatry. 2002;159:1752-1759.[Evans 2002]

Fantry LE, Zhan M, Taylor GH, Sill AM, Flaws JA. Age of menopause and menopausal symptoms in HIVinfected women. AIDS Patient Care STDS. 2005;19:703-711.[Fantry 2005]

Fastring DR, Amedee A, Gatski M, et al. Co-occurrence of Trichomonas vaginalis and Bacterial Vaginosis and
Vaginal Shedding of HIV-1 RNA. Sex Transm Dis. 2014;41:173-179.[Fastring 2014]

Fialho RM, Pereira M, Mendona N, et al. Depressive symptoms and neurocognitive performance among HIVinfected women. Women Health. 2013;53(2):117-134. doi: 10.1080/03630242.2013.767301.[Fialho 2013]

Firnhaber C, Wilkin T. Human papillomavirus vaccines: where do they fit in HIV-infected individuals? Curr
HIV/AIDS Rep. 2012 Sep;9(3):278-286. doi: 10.1007/s11904-012-0128-6.[Firnhaber 2012]

Ford N, Mofenson L, Kranzer K, et al. Safety of efavirenz in first-trimester of pregnancy: a systematic review
and meta-analysis of outcomes from observational cohorts. AIDS. 2010;24:1461-1470.[Ford 2010]

Foster R, Taylor C, Everall IP. More on abacavir-induced neuropsychiatric reactions. AIDS.


2004;18:2449.[Foster 2004]

Fat distribution in women with HIV infection. J Acquir Immune Defic Syndr. 2006;42:562-571.[FRAM 2006]

Freiberg MS, Chang CC, Kuller LH, et al. HIV infection and the risk of acute myocardial infarction. JAMA Intern
Med. 2013; Apr 22;173(8):614-22.[Freiberg 2013]

FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical
lesions. N Engl J Med. 2007;356:1915-1927.[FUTURE II 2007]

Gold EB, Bromberger J, Crawford S, et al. Factors associated with age at natural menopause in a multiethnic
sample of midlife women. Am J Epidemiol. 2001;153:865-874.[Gold 2001]

Goldie SJ, Freedberg KA, Weinstein MC, Wright TC, Kuntz KM. Cost effectiveness of human papillomavirus
testing to augment cervical cancer screening in women infected with the human immunodeficiency virus. Am J
Med. 2001;111:140-149.[Goldie 2001]

Gollub E, Stein Z. Living with uncertainty: acting in the best interests of women. AIDS Res Treat.
2012;2012:524936. doi: 10.1155/2012/524936. Epub 2012 Nov 1.[Gollub 2012]

Gray RH, Li X, Kigozi G, et al. Increased risk of incident HIV during pregnancy in Rakai, Uganda: a prospective
study. Lancet. 2005;366:1182-1188.[Gray 2005]

Greig JM, Anderson J. Optimizing antiretroviral therapy for women living with HIV. Curr Opin Infect Dis.
2014;27:46-52.[Greig 2014]

Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared
with immunosuppressed transplant recipients: a meta-analysis. Lancet 2007;370:59-67.[Grulich 2007]

Guaraldi G, Stentarelli C, Domingues Da Silva A, et al. Metabolic alterations in HIV-infected pregnant women:
moving to metabolic tailoring of antiretroviral drugs. AIDS Rev. 2014;16:14-22.[Guaraldi 2014]

Harpaz R, Ortega-Sanchez IR, Seward JF; Advisory Committee on Immunization Practices (ACIP) Centers for
Disease Control and Prevention (CDC). Prevention of herpes zoster: recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008;57(RR-5):1-30; quiz CE24.[Harpaz 2008]

Harris TG, Burk RD, Palefsky JM, et al. Incidence of cervical squamous intraepithelial lesions associated with
HIV serostatus, CD4 cell counts, and human papillomavirus test results. JAMA. 2005;293:1471-1476.[Harris
2005]

Hawes SE, Critchlow CW, Faye Niang MA, et al. Increased risk of high-grade cervical squamous intraepithelial
lesions and invasive cervical cancer among African women with human immunodeficiency virus type 1 and 2
infections. J Infect Dis. 2003;188:555-563.[Hawes 2003]

Heard I, Tassie JM, Kazatchkine MD, Orth G. Highly active antiretroviral therapy enhances regression of
cervical intraepithelial neoplasia in HIV-seropositive women. AIDS. 2002;16:1799-1802.[Heard 2002]

Heffron R, Donnell D, Rees H, et al. Use of hormonal contraceptives and risk of HIV-1 transmission: a
prospective cohort study. Lancet Infect Dis. 2012;12:19-26.[Heffron 2012]

Heffron R, Mugo N, Ngure K, Celum C, Donnell D, Were E, Rees H, Kiarie J, Baeten JMet al; Partners in
Prevention HSVHIV Transmission Study Team. Hormonal contraceptive use and risk of HIV-1 disease
progression. AIDS. 2013;27:261-267.[Heffron 2013]

Himelhoch S, Medoff DR, Oyeniyi G. Efficacy of group psychotherapy to reduce depressive symptoms among
HIV-infected individuals: a systematic review and meta-analysis. AIDS Patient Care STDS. 2007;21:732739.[Himelhoch 2007]

Hitti J, Frenkel LM, Stek AM, et al. Maternal toxicity with continuous nevirapine in pregnancy: results from
PACTG 1022. J Acquir Immune Defic Syndr. 2004;36:772-776.[Hitti 2004]

Hodder S, Arasteh K, De Wet J, et al. Effect of gender and race on the week 48 findings in treatment-naive,
HIV-1-infected patients enrolled in the randomized, phase III trials ECHO and THRIVE. HIV Med. 2012;13:406415.[Hodder 2012]

Hoffman R, Vardavas R, Jaycocks A, et al. The benefits of pre-exposure prophylaxis as an adjunctive method
of HIV-1 prevention during attempted conception between HIV-1-uninfected women and HIV-1-infected male
partners: a modeling approach. Program and abstracts of the 7th Annual IAS Conference on HIV
Pathogenesis, Treatment and Prevention; June 30 - July 3, 2013; Kuala Lumpur, Malaysia. Abstract
TUAC0104.[Hoffman 2013]

Holcomb K, Maiman M, Dimaio T, Gates J. Rapid progression to invasive cervix cancer in a woman infected
with the human immunodeficiency virus. Obstet Gynecol. 1998;91:848-850.[Holcomb 1998]

Horberg MA, Silverberg MJ, Hurley LB, et al. Effects of depression and selective serotonin reuptake inhibitor
use on adherence to highly active antiretroviral therapy and on clinical outcomes in HIV-infected patients. J
Acquir Immune Defic Syndr. 2008;47:384-390.[Horberg 2008]

Ickovics JR, Hamburger ME, Vlahov D, et al. Mortality, CD4 cell count decline, and depressive symptoms
among HIV-seropositive women: longitudinal analysis from the HIV Epidemiology Research Study. JAMA.
2001;285:1466-1474.[Ickovics 2001]

Illangasekare SL, Burke JG, McDonnell KA, et al. The impact of intimate partner violence, substance use, and
HIV on depressive symptoms among abused low-income urban women. J Interpers Violence. 2013;28:28312848.[Illangasekare 2013a]

Illangasekare S, Burke J, Chander G, et al. The syndemic effects of intimate partner violence, HIV/AIDS, and
substance abuse on depression among low-income urban women. J Urban Health. 2013;90:934947.[Illangasekare 2013b]

Imai K, Sutton MY, Mdodo R, Del Rio C. HIV and menopause: a systematic review of the effects of HIV
infection on age at menopause and the effects of menopause on response to antiretroviral therapy. Obstet
Gynecol Int. 2013;2013:340309.[Imai 2013]

Ironson G, O'Cleirigh C, Fletcher MA, et al. Psychosocial factors predict CD4 and viral load change in men and
women with human immunodeficiency virus in the era of highly active antiretroviral treatment. Psychosom
Med. 2005;67:1013-1021.[Ironson 2005]

Jones S, de Gijsel D, Wallach FR, et al. Utility of QuantiFERON-TB Gold in-tube testing for latent TB infection
in HIV-infected individuals. Int J Tuberc Lung Dis. 2007;11:1190-1195.[Jones 2007]

Judd FK, Cockram AM, Komiti A, Mijch AM, Hoy J, Bell R. Depressive symptoms reduced in individuals with
HIV/AIDS treated with highly active antiretroviral therapy: a longitudinal study. Aust N Z J Psychiatry.
2000;34:1015-1021.[Judd 2000]

Kahn JA, Xu J, Kapogiannis BG, et al. immunogenicity and safety of the human papillomavirus 6, 11, 16, 18
vaccine in HIV-infected young women. Clin Infect Dis. 2013;57:735-744.[Kahn 2013]

Kanapathipillai R, Hickey M, Giles M. Human immunodeficiency virus and menopause. Menopause.


2013;20:983-990.[Kanapathipillai 2013]

Kaplan RC, Kingsley LA, Sharrett AR, et al. Ten-year predicted coronary heart disease risk in HIV-infected
men and women. Clin Infect Dis. 2007;45:1074-1081.[Kaplan 2007]

Karim R, Mack WJ, Kono N, et al. Gonadotropin and sex steroid levels in HIV-infected premenopausal women
and their association with subclinical atherosclerosis in HIV-infected and -uninfected women in the women's
interagency HIV study (WIHS). J Clin Endocrinol Metab. 2013;98:E610-E618.[Karim 2013]

Kieffer MP, Nhlabatsi B, Mahdi M, Improved detection of incident HIV infection and uptake of PMTCT services
in labor and delivery in a high HIV prevalence setting. J Acquir Immune Defic Syndr. 2011;57:e85-91.[Kieffer
2011]

Kilmarx PH, Limpakarnjanarat K, Kaewkungwal J, et al. Disease progression and survival with human
immunodeficiency virus type 1 subtype E infection among female sex workers in Thailand. J Infect Dis.
2000;181:1598-1606.[Kilmarx 2000]

Kitchener H, Nelson L, Adams J, et al. Colposcopy is not necessary to assess the risk to the cervix in HIVpositive women: an international cohort study of cervical pathology in HIV-1 positive women. Int J Cancer.
2007;121:2484-2491.[Kitchener 2007]

Kojic EM, Wang CC, Cu-Uvin S. HIV and menopause: a review. J Womens Health (Larchmt). 2007;16:14021411.[Kojic 2007]

Kojic EM, et al. Baseline seroprevalence of HPV vaccine types 6, 11, 16, and 18 in HIV+ women receiving the
quadrivalent vaccine in the AIDS Clinical Trials Group Study A5240. Program and abstracts of the 18th
Conference on Retroviruses and Opportunistic Infections; February 27 March 2, 2011; Boston,
Massachusetts. Abstract 762.[Kojic 2011a]

Kojic EM, Cu-Uvin S, Conley L, et al. Human papillomavirus infection and cytologic abnormalities of the anus
and cervix among HIV-infected women in the study to understand the natural history of HIV/AIDS in the era of
effective therapy (the SUN study). Sex Transm Dis. 2011;38:253-259.[Kojic 2011b]

Kojic EM, Kang M, Cespedes MS, et al. Immunogenicity and Safety of a Quadrivalent Human Papillomavirus
Vaccine in HIV-1-Infected Women. Clin Infect Dis. 2014;[Epub ahead of print].[Kojic 2014]

Kowada A. Cost effectiveness of interferon- release assay for TB screening of HIV positive pregnant women
in low TB incidence countries. J Infect. 2014;68:32-42.[Kowada 2014]

Kunimoto D, Der E, Beckon A, et al. Use of the QuantiFERON-TB Gold test to confirm latent tuberculosis
infection in a Canadian tuberculosis clinic. Int J Tuberc Lung Dis. 2009;13:726-730.[Kunimoto 2006]

Landolt NK, Phanuphak N, Ubolyam S, et al. Efavirenz, in contrast to nevirapine, is associated with
unfavorable progesterone and antiretroviral levels when coadministered with combined oral contraceptives. J
Acquir Immune Defic Syndr. 2013;62:534-539.[Landolt 2013]

Lavreys L, Baeten JM, Martin HL, Jr, et al. Hormonal contraception and risk of HIV-1 acquisition: results of a
10-year prospective study. AIDS. 2004;18:695-697.[Lavreys 2004]

Leticee N, Viard JP, Yamgnane A, Karmochkine M, Benachi A. Contraceptive failure of etonogestrel implant in
patients treated with antiretrovirals including efavirenz. Contraception. 2012;85:425-427.[Leticee 2012]

Li Y, Marshall CM, Rees HC, Nunez A, Ezeanolue EE, Ehiri JE. Intimate partner violence and HIV infection
among women: a systematic review and meta-analysis. J Int AIDS Soc. 2014;17:18845.[Li 2014]

Lillie-Blanton M, Stone VE, Snow Jones A, et al. Association of race, substance abuse, and health insurance
coverage with use of highly active antiretroviral therapy among HIV-infected women, 2005. Am J Public Health.
2010;100:1493-1499.[Lillie-Blanton 2010]

Low-Beer S, Chan K, Yip B, et al. Depressive symptoms decline among persons on HIV protease inhibitors. J
Acquir Immune Defic Syndr. 2001;23:295-301.[Low-Beer 2000]

Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy in a large urban clinic: risk factors for
virologic failure and adverse drug reactions. Ann Intern Med. 1999;131:81-87.[Lucas 1999]

Lundgren JD, Babiker A, El-Sadr W, et al; Strategies for Management of Antiretroviral Therapy (SMART) Study
Group. Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in
the SMART study: role of CD4+ cell counts and HIV RNA levels during follow-up. J Infect Dis. 2008;197:11451155.[Lundgren 2008]

Lutalo T, Musoke R, Kong X, et al. Effects of hormonal contraceptive use on HIV acquisition and transmission
among HIV-discordant couples. AIDS. 2013;27(suppl 1):S27-S34.[Lutalo 2013]

Mallari AO, Schwartz TM, Luque AE, et al. Anal cancer screening in HIV-infected patients: is it time to screen
them all? Dis Colon Rectum. 2012;55:1244-1250.[Mallari 2012]

Massad LS, DSouza G, Tian F, et al. Negative predictive value of pap testing: implications for screening
intervals for women with human immunodeficiency virus. Obstet Gynecol. 2012;120:791-797.[Massad 2012]

Matheson PB, Thomas PA, Abrams EJ, et al. Heterosexual behavior during pregnancy and perinatal
transmission of HIV-1. AIDS. 1996;10:1249-1256.[Matheson 1996]

Maxwell S, Scheftner WA, Kessler HA, et al. Manic syndrome associated with zidovudine. JAMA.
1988;259:3406-3407.[Maxwell 1988]

Mazhude C, Jones S, Murad S, Taylor C, Easterbrook P. Female sex but not ethnicity is a strong predictor of
non-nucleoside reverse transcriptase inhibitor-induced rash. AIDS. 2002;16: 1566-1568.[Mazhude 2002]

McCoy SI, Zheng W, Montgomery ET, et al. Oral and injectable contraception use and risk of HIV acquisition
among women in sub-Saharan Africa. AIDS. 2013;27:1001-1009.[McCoy 2013]

McLean HQ, Fiebelkorn AP, Temte JL, et al. Prevention of measles, rubella, congenital rubella syndrome, and
mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP).
MMWR Recomm Rep. 2013;62:1-34.[McLean 2013]

Meditz AL, MaWhinney S, Allshouse A, et al. Sex, race, and geographic region influence clinical outcomes
following primary HIV-1 infection. J Infect Dis. 2011;203:442-451.[Meditz 2011]

Mildvan D, Yarrish R, Marshak A, et al. Pharmacokinetic interaction between nevirapine and ethinyl
estradiol/norethindrone when administered concurrently to HIV-infected women. J Acquir Immune Defic Syndr.
2002;29:471-477.[Mildvan 2002]

Mills AM, Nelson M, Jayaweera D, et al. Once-daily darunavir/ritonavir vs. lopinavir/ritonavir in treatment-naive,
HIV-1-infected patients: 96-week analysis. AIDS. 2009;23:1679-1688.[Mills 2009]

Mocroft A, Gill MJ, Davidson W, Phillips AN. Are there gender differences in starting protease inhibitors,
HAART, and disease progression despite equal access to care? J Acquir Immune Defic Syndr. 2000;24:475482.[Mocroft 2000]

Mofenson LM, Lambert JS, Stiehm ER, et al. Risk factors for perinatal transmission of human
immunodeficiency virus type 1 in women treated with zidovudine. N Engl J Med. 1999;341:385-393.[Mofenson
1999]

Molina JM, Andrade-Villanueva J, Echevarria J, et al. Once-daily atazanavir/ritonavir compared with twice-daily
lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive
HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE Study. J Acquir Immune Defic
Syndr. 2010;53:323-332.[Molina 2010]

Moore AL, Kirk O, Johnson AM, Katlama C, et al. Virologic, immunologic, and clinical response to highly active
antiretroviral therapy: the gender issue revisited. J Acquir Immune Defic Syndr. 2003;32:452-461.[Moore 2003]

Morrison MF, Petitto JM, Ten Have T, et al. Depressive and anxiety disorders in women with HIV infection. Am
J Psychiatry. 2002;159:789-796.[Morrison 2002]

Morrison CS, Skoler-Karpoff S, Kwok C, et al. Hormonal contraception and the risk of HIV acquisition among
women in South Africa. AIDS. 2012;26:497-504.[Morrison 2012]

Mullins TL, Wilson CM, Rudy BJ, Sucharew H, Kahn JA. Incident anal human papillomavirus and human
papillomavirus-related sequelae in HIV-infected versus HIV-uninfected adolescents in the United States. Sex
Transm Dis. 2013;40:715-720.[Mullins 2013]

Nanda K, Amaral E, Hays M, Viscola MA, Mehta N, Bahamondes L. Pharmacokinetic interactions between
depot medroxyprogesterone acetate and combination antiretroviral therapy. Fertil Steril. 2008;90:965971.[Nanda 2008]

Noguchi LM, Richardson B, Chirenje Z, et al. Injectable contraception and HIV acquisition in the VOICE study
(MTN-003). Program and abstracts of the 21st Conference on Retroviruses and Opportunistic Infections;
March 3-6, 2014; Boston, Massachusetts. Abstract 847.[Noguchi 2014]
ODowd MA, McKegney F. Manic syndrome associated with zidovudine. JAMA. 1988;260:3587.[ODowd 1988]

Ouellet D, Hsu A, Qian J, et al. Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy
female volunteers. Br J Clin Pharmacol. 1998;46:111-116.[Ouellet 1998]

Paavonen J, Naud P, Salmern J, et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted


vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of
a double-blind, randomised study in young women. Lancet. 2009;374:301-314.[Paavonen 2009]

Parmigiani A, Alcaide ML, Freguja R, et al. Impaired antibody response to influenza vaccine in HIV-infected
and uninfected aging women is associated with immune activation and inflammation. PLoS One.
2013;8:e79816.[Parmigiani 2013]

Patterson K, Napravnik S, Eron J, Keruly J, Moore R. Effects of age and sex on immunological and virological
responses to initial highly active antiretroviral therapy. HIV Med. 2007;8:406-410.[Patterson 2007]

Patterson KB, Cohn SE, Uyanik J, Hughes M, Smurzynski M, Eron JJ. Treatment responses in antiretroviral
treatment-naive premenopausal and postmenopausal HIV-1-infected women: an analysis from AIDS Clinical
Trials Group Studies. Clin Infect Dis. 2009;49:473-476.[Patterson 2009]

Patterson KB, Dumond JB, Prince HA, et al. Protein binding of lopinavir and ritonavir during 4 phases of
pregnancy: implications for treatment guidelines. J Acquir Immune Defic Syndr. 2013;63:51-58.[Patterson
2013]

Pence BW, Miller WC, Gaynes BN, Eron JJ Jr. Psychiatric illness and virologic response in patients initiating
highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2007;44:159-166.[Pence 2007]

Pernerstorfer-Schoen H, Jilma B, Perschler A, et al. Sex differences in HAART-associated dyslipidaemia.


AIDS. 2001;15:725-734.[Pernerstorfer-Schoen 2001]

Phillips SJ, Curtis KM, Polis CB. Effect of hormonal contraceptive methods on HIV disease progression: a
systematic review. AIDS. 2013 Mar 13;27(5):787-794. doi: 10.1097/QAD.0b013e32835bb672.[Phillips 2013]

Phiri K, Hernandez-Diaz S, Dugan KB, et al. First trimester exposure to antiretroviral therapy and risk of birth
defects. Pediatr Infect Dis J. 2014;[Epub ahead of print].[Phiri 2014]

Pillai NV, Kupprat SA, Halkitis PN. Impact of service delivery model on health care access among HIV-positive
women in New York City. AIDS Patient Care STDS. 2009;23:51-58.[Pillai 2009]

Polis CB, Westreich D, Balkus JE, Heffron R; Participants of the 2013 HC-HIV Observational Analysis Meeting.
Assessing the effect of hormonal contraception on HIV acquisition in observational data: challenges and
recommended analytic approaches. AIDS. 2013;27(suppl 1):S35-S43.[Polis 2013a]

Polis CB, Phillips SJ, Curtis KM. Hormonal contraceptive use and female-to-male HIV transmission: a
systematic review of the epidemiologic evidence. AIDS. 2013;27:493-505.[Polis 2013b]

Polis CB,Curtis KM. Use of hormonal contraceptives and HIV acquisition in women: a systematic review of the
epidemiological evidence. Lancet Infect Dis. 2013;13:797-808.[Polis 2013c]

Powis KM, Kitch D, Ogwu A, et al. Increased risk of preterm delivery among HIV-infected women randomized
to protease versus nucleoside reverse transcriptase inhibitor-based HAART during pregnancy. J Infect Dis.
2011;204:506-514.[Powis 2011]

Prins M, Meyer L, Hessol NA. Sex and the course of HIV infection in the pre- and highly active antiretroviral
therapy eras. AIDS. 2005;19:357-370.[Prins 2005]

Rachas A, Warszawski J, Le Chenadec J, et al. Does pregnancy affect the early response to cART? AIDS.
2013;27:357-367.[Rachas 2013]

Redelman-Sidi G, Sepkowitz KA. IFN- release assays in the diagnosis of latent tuberculosis infection among
immunocompromised adults. Am J Respir Crit Care Med. 2013;188:422-431.[Redelman-Sidi 2013]

Richardson BA, Otieno PA, Mbori-Ngacha D, Overbaugh J, Farquhar C, John-Stewart GC. Hormonal
contraception and HIV-1 disease progression among postpartum Kenyan women. AIDS. 2007;21:749753.[Richardson 2007]

Robinson WR, Barnes SE, Adams S, Perrin MS. Histology/cytology discrepancies in HIV-infected obstetric
patients with normal pap smears. Gynecol Oncol. 1997;65:430-433.[Robinson 1997]

Robinson JA, Jamshidi R, Burke AE. Contraception for the HIV-positive woman: a review of interactions
between hormonal contraception and antiretroviral therapy. Infect Dis Obstet Gynecol.
2012;2012:890160.[Robinson 2012]

Rochat TJ, Tomlinson M, Newell ML, Stein A. Detection of antenatal depression in rural HIV-affected
populations with short and ultrashort versions of the Edinburgh Postnatal Depression Scale (EPDS). Arch
Womens Ment Health. 2013;16:401-410.[Rochat 2013]

Rodriguez EM, Mofenson LM, Chang BH, et al. Association of maternal drug use during pregnancy with
maternal HIV culture positivity and perinatal HIV transmission. AIDS. 1996;10:273-282.[Rodriguez 1996]

Sanne I, Mommeja-Marin H, Hinkle J, et al. Severe hepatotoxicity associated with nevirapine use in HIVinfected subjects. J Infect Dis. 2005;191:825-829.[Sanne 2005]

Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MRI as an
adjunct to mammography. CA Cancer J Clin. 2007;57:75-89.[Saslow 2007]

Saslow D, Solomon D, Lawson HW, et al; ACS-ASCCP-ASCP Cervical Cancer Guideline Committee.
American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for
Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J
Clin. 2012;62:147-172.[Saslow 2012]

Sauzullo I, Mengoni F, Scrivo R, et al. Evaluation of QuantiFERON-TB Gold In-Tube in human


immunodeficiency virus infection and in patient candidates for anti-tumour necrosis factor-alpha treatment. Int J
Tuberc Lung Dis. 2010;14:834-840.[Sauzullo 2010]

Schaerf FW, Miller R, Pearlson GD, et al. Manic syndrome associated with zidovudine. JAMA. 1988;260:35873588.[Schaerf 1988]

Schoenbaum EE, Hartel D, Lo Y, et al. HIV infection, drug use, and onset of natural menopause. Clin Infect
Dis. 2005;41:1517-1524.[Schoenbaum 2005]

Serrano-Villar S, Estrada V, Gmez-Garre D, et al. Diagnosis of subclinical atherosclerosis in HIV-infected


patients: higher accuracy of the D:A:D risk equation over Framingham and SCORE algorithms. Eur J Prev
Cardiol. 2012;[Epub ahead of print].[Serrano-Villar 2012]

Shapiro DE, Sperling RS, Mandelbrot L, Britto P, Cunningham BE. Risk factors for perinatal human
immunodeficiency virus transmission in patients receiving zidovudine prophylaxis. Pediatric AIDS Clinical Trials
Group protocol 076 Study Group. Obstet Gynecol. 1999;94:897-908.[Shapiro 1999]

Silverberg MJ, Neuhaus J, Bower M, et al. Risk of cancers during interrupted antiretroviral therapy in the
SMART study. AIDS. 2007 Sep 12;21:1957-1963.[Silverberg 2007]

Smith KP, Christakis NA. Association between widowhood and risk of diagnosis with a sexually transmitted
infection in older adults. Am J Public Health. 2009;99:2055-2062.[Smith 2009]

Smith KY, Tierney C, Mollan K, et al. Outcomes by sex following treatment initiation with atazanavir plus
ritonavir or efavirenz with abacavir/lamivudine or tenofovir/emtricitabine. Clin Infect Dis. 2014;58:555563.[Smith 2014]

Soals C, Gagineu MC, Ravaux I, et al. Population pharmacokinetics of atazanavir in human immunodeficiency
virus-infected patients. Ther Drug Monit. 2008;30:670-673.[Soals 2008]

Song I, Mark S, Borland J, et al. Dolutegravir has no effect on the pharmacokinetics of methadone or oral
contraceptives with norgestimate and ethinyl estradiol. Program and abstracts of the 20th Conference on
Retroviruses and Opportunistic Infections; March 3-6, 2013; Atlanta, Georgia. Abstract 535.[Song 2013]

Soon GG, Min M, Struble KA, et al. Meta-analysis of gender differences in efficacy outcomes for HIV-positive
subjects in randomized controlled clinical trials of antiretroviral therapy (2000-2008). AIDS Patient Care STDS.
2012;26:444-453.[Soon 2012]

Sow PS, Watson-Jones D, Kiviat N, et al. Safety and immunogenicity of human papillomavirus-16/18 AS04adjuvanted vaccine: a randomized trial in 10-25-year-old HIV-seronegative African girls and young women. J
Infect Dis. 2013;207:1753-1763.[Sow 2013]

Squires K, Lazzarin A, Gatell JM, et al. Comparison of once-daily atazanavir with efavirenz, each in
combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV. J
Acquir Immune Defic Syndr 2004;36:1011-1019.[Squires 2004]

Squires K, Bekker L, Eron J, et al. Safety, tolerability, and efficacy of raltegravir in a diverse cohort of HIVinfected patients: 48-week results from the REALMRK study. AIDS Res Hum Retroviruses. 2013;29:859870.[Squires 2013]

Stall R, Catania J. AIDS risk behaviors among late middle-aged and elderly Americans: the National-AidsBehavioral-Surveys. Arch Intern Med. 1994;154:57-63.
[Stall 1994]

Sterling TR, Vlahov D, Astemborski J, Hoover DR, Margolick JB, Quinn TC. Initial plasma HIV-1 RNA levels
and progression to AIDS in women and men. N Engl J Med. 2001;344:720-725.[Sterling 2001]

Stringer EM, Levy J, Sinkala M, Chi BH, Matongo I, Chintu N, Stringer JS. HIV disease progression by
hormonal contraceptive method: secondary analysis of arandomized trial. AIDS. 2009;23:1377-1382.[Stringer
2009]

Thurman AR, Anderson S, Doncel GF. Effects of hormonal contraception on antiretroviral drug metabolism,
pharmacokinetics and pharmacodynamics. Am J Reprod Immunol. 2014;[Epub ahead of print].[Thurman 2014]

Aptivus [package insert]. Ridgefield, CT: Boehringer Ingelheim; April 2012.[Tipranavir PI]

Toft L, Storgaard M, Mller M, et al. Comparison of the immunogenicity and reactogenicity of Cervarix and
Gardasil human papillomavirus vaccines in HIV-infected adults: a randomized, double-blind clinical trial. J
Infect Dis. 2014;209:1165-1173.[Toft 2014]

Torti C, Quiros-Roldan ME, Cologni G, et al. Plasma HIV load and proviral DNA decreases after two standard
antiretroviral regimens in HIV-positive patients naive to antiretrovirals. Curr HIV Res. 2008;6:43-48.[Torti 2008]

Townsend CL, Cortina-Borja M, Peckham CS, et al. Low rates of mother-to-child transmission of HIV following
effective pregnancy interventions in the United Kingdom and Ireland, 2000-2006. AIDS. 2008;22:973981.[Townsend 2008]

Tseng A, Hills-Nieminen C. Drug interactions between antiretrovirals and hormonal contraceptives. Expert
Opin Drug Metab Toxicol. 2013;9:559-572.[Tseng 2013]

Turner BJ, Hauck WW, Fanning TR, Markson LE. Cigarette smoking and maternal-child HIV transmission. J
Acquir Immune Defic Syndr Hum Retrovirol. 1997;14:327-337.[Turner 1997]

Umeh OC, Currier JS, Park JG, Cramer Y, Hermes AE, Fletcher CV. Sex differences in lopinavir and ritonavir
pharmacokinetics among HIV-infected women and men. J Clin Pharmacol. 2011;51:1665-1673.[Umeh 2011]

US National Cancer Institute. Cervical cancer treatment PDQ. March 14, 2014. Available at:
http://www.cancer.gov/cancertopics/pdq/treatment/cervical/healthprofessional/. Accessed April 11,
2014.[USNCI Cervical]

Volkow P, Rubi S, Lizano M, et al. High prevalence of oncogenic human papillomavirus in the genital tract of
women with human immunodeficiency virus. Gynecol Oncol. 2001;82:27-31[Volkov 2001]

Watts DH, Park JG, Cohn SE, et al. Safety and tolerability of depot medroxyprogesterone acetate among HIVinfected women on antiretroviral therapy: ACTG A5093. Contraception. 2008;77:84-90.[Watts 2008]

Westling K, Pettersson K, Kaldma A, Navr L. Rapid decline in HIV viral load when introducing raltegravircontaining antiretroviral treatment late in pregnancy. AIDS Patient Care STDS. 2012 Dec;26(12):714-717. doi:
10.1089/apc.2012.0283. Epub 2012 Oct 26.[Westling 2012]

World Health Organization/WHO CONRAD. Technical consultation on nonoxynol 9, 2001. Available at:
http://whqlibdoc.who.int/hq/2003/WHO_RHR_03.08.pdf. Accessed April 11, 2014.[WHO 2001]

World Health Organization. Antiretroviral drugs for treating pregnant women and preventing HIV infection in
infants in resource-limited settings: towards universal access, recommendations for a public health approach
(2010 version). Available at: http://www.who.int/hiv/pub/mtct/antiretroviral2010/en/. Accessed April 11,
2014.[WHO 2010]

World Health Organization. WHO guidelines approved by the Guidelines Review Committee. Hormonal
contraception and HIV: technical statement. Feb 2012. Available at:
http://whqlibdoc.who.int/hq/2012/WHO_RHR_12.08_eng.pdf. Accessed April 11, 2014.[WHO 2012]

World Health Organization. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and
Preventing HIV Infection: Recommendations for a Public Health Approach. June 2013. Available at:
http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf. Accessed April 11, 2014.[WHO HIV]

Wise ME, Mistry K, Reid S. Neuropsychiatric complications of nevirapine treatment. BMJ. 2002:324:879.[Wise
2002]

Wright TC Jr, Ellerbrock TV, Chiasson MA, et al. Cervical intraepithelial neoplasia in women infected with
human immunodeficiency virus: prevalence, risk factors, and validity of Papanicolaou smears. Obstet Gynecol.
1994;84:591-597.[Wright 1994a]

Wright TC Jr, Koulos J, Schnoll F, et al. Cervical intraepithelial neoplasia in women infected with the human
immunodeficiency virus: outcome after loop electrosurgical excision. Gynecol Oncol. 1994;55:53-58.[Wright
1994b]

Zablotsky D, Kennedy M. Risk factors and HIV transmission to midlife and older women: knowledge, options,
and the initiation of safer sexual practices. J Acquir Immune Defic Syndr. 2003;33(suppl 2):S122S130.[Zablotsky 2003]

Zorrilla CD, Wright R, Osiyemi OO, et al. Total and unbound darunavir pharmacokinetics in pregnant women
infected with HIV-1: results of a study of darunavir/ritonavir 600/100 mg administered twice daily. HIV Med.
2014;15:50-56.[Zorrilla 2014]

Keywords: Women