INTERNAL

HUMAN IMMUNODEFICIENCY VIRUS (HIV)

MEDICINE MICHELLE CARANDANG-CUVIN, M.D., FPPS, FPIDSP
AY 2021-2022 02/09/2022
Hematology Module
• Hugging
• Mosquitoes, ticks, or other insects
TOPIC OUTLINE • HIV does not survive long outside the human body (such as
I. HIV on surfaces), and it cannot reproduce outside a human host.
a. HIV Transmission
b. Ways HIV is NOT Transmitted c. Factors that Increase HIV Risk
c. Factors that increase HIV risk 1. VIRAL LOAD
• The higher someone’s viral load, the more likely that
II. Stages of HIV
person is to transmit HIV
a. Stage 1: Acute HIV Infection
• Viral load is the amount of HIV in the blood of someone
b. Stage 2: Clinical Latency who has HIV
c. Stage 3: AIDS • Viral load is highest during the acute phase of HIV and
III. Diagnosis without HIV treatment
IV. Post HIV Test Counseling • Taking HIV medicine can make the viral load very low—
V. Antiretroviral Therapy so low that a test can’t detect it (called an undetectable
VI. HIV Support Groups viral load).
• People with HIV who keep an undetectable viral load (or
LEARNING OBJECTIVES stay virally suppressed) can live long, healthy lives.
1. To discuss the diagnostics and management of • Having an undetectable viral load also helps prevent
transmitting the virus to others through sex or sharing
HIV/AIDS
needles, syringes, or other injection equipment, and from
mother to child during pregnancy, birth, and
LEGEND: breastfeeding.
Clinical Guide
PPT Lecturer Book
Correlation/SGDs Questions 2. OTHER SEXUALLY TRASMITTED DISEASES
• ❖ • More likely to get or transmit HIV
• Using protective barriers (i.e. condoms)
o Can reduce chances of getting or transmitting STDs
HUMAN IMMUNODEFICIENCY VIRUS (HIV) that can be transmitted through genital fluids,
• HIV (human immunodeficiency virus) is a virus that such as gonorrhea, chlamydia, and HIV.
attacks the body’s immune system. o Less effective at preventing STDs that can be
• If not treated, it can lead to AIDS (Acquired transmitted through sores or cuts on the skin,
Immunodeficiency Syndrome). like human papillomavirus, genital herpes, and
• There is currently no effective cure. Once people get HIV, syphilis.
they have it for life.
• But with proper medical care, HIV can be controlled. 3. ALCOHOL AND DRUG USE
People with HIV who get effective HIV treatment can live • When a person is drunk or high, the more likely to engage
long, healthy lives and protect their partners. in risky sexual behaviors like having sex without
• A Retrovirus, a member of genus Lentivirus protection (such as condoms or medicine to prevent or
• Two species of HIV: HIV-1 and HIV-2 treat HIV).
o Both responsible for the development of AIDS, • Being drunk or high affects your ability to make safe
but transmission patterns, demographics, and choices.
disease progression are different. • Drinking alcohol, particularly binge drinking, and using
o HIV-1: more prevalent pathogenic species “club drugs” can alter once judgment, lower inhibitions,
and impair decisions about sex or drug use.
a. HIV Transmission • More likely to have unplanned sex, have a harder time
• Unprotected sex using a barrier right away, have more sexual partners, or
• Pregnancy, childbirth, and breastfeeding use other drugs.
• Injecting drugs
• Working in healthcare STAGES OF HIV
• Blood transfusion and organ/tissue transplants
a. Stage 1: Acute HIV Infection (Acute Retroviral
b. Ways HIV is NOT Transmitted Syndrome)
• Sharing dishes • Within 2 to 4 weeks after infection with HIV
• Saliva • Fever, lymphadenopathy, sore throat, myalgia, diarrhea,
• Tears headache and skin rash (often described as
• Sweat mononucelosis-like illness), may last for a few weeks
• Shaking hands • ~60% are asymptomatic
• Through the air • Period of rapid viral replication and infection of CD4 cells
• Sharing toilet seats -> plasma viral RNA level is typically very high
• Closed mouth kissing
 INTERNAL MEDICINE
Fig. 1 Acute Retroviral Syndrome signs and symptoms
b. Stage 2: Clinical Latency (HIV Inactivity or
Dormancy)
• Asymptomatic HIV infection or Chronic HIV Infection
• May not have any symptoms or get sick during this time
o For people who aren’t taking medicine to treat
HIV, this period can last a decade or longer, but
some may progress faster. They can transmit
HIV to others
o For people who are on ART and stay virally
suppressed, less likely to transmit
• At the end of this phase, viral load starts to go up and CD4
cell count begins to go down, they may begin to have
symptoms and the person moves into Stage 3.
Fig. 2 HIV Disease Progression Pattern
c. Stage 3: Acquired Immunodeficiency Syndrome
(AIDS)
• AIDS is the most severe phase of HIV infection and
consequent depletion of CD4 count.
• AIDS is defined as a CD4 cell count <200 cells/uL or the
presence of any *AIDS-defining conditions regardless
of the CD4 count
• Advanced HIV infection refer to infection when CD4
cell count is <50 cell/uL.
• Badly damaged immune systems that they get an
increasing number of severe illnesses → opportunistic
infections
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HUMAN IMMUNODEFICIENCY VIRUS (HIV)
• Without treatment, the median survival of patients
with advanced HIV infection is 12 to 18 mos.
• Common symptoms: chills, fever, lymphadenopathies,
weakness, and weight loss
• Have high viral load and be very infectious
Fig. 3 Main symptoms of AIDS
AIDS-DEFINING ILLNESSES IN HIV INFECTION
• Bacterial infections, multiple or recurrent
• Candidiasis of bronchi, trachea or lungs or esophagus
• Cervical cancer, invasive
• Coccidiomycosis, disseminated or extrapulmonary
• Cryptococcosis, extrapulmonary
• Cryptosporidiosis, chronic intestinal (>1 mo duration)
• CMV disease (other that liver, spleen or nodes), onset at
age >1 month
• CMV retinitis with loss of vision
• Encephalopathy attributed to HIV
• HSV: chronic ulcers (>1 mo duration) or bronchitis,
pneumonitis or esophagitis (onset at age>1 mo)
• Histoplasmosis, disseminated or extrapulmonary
• Isosporiasis, chronic intestinal (>1 mo duration)
• Kaposi sarcoma
• Lymphoma, Burkitt; immunoblastic; primary of brain
• MAC or Mycobacterium kansaii, disseminated or
extrapulmonary
• Mycobacterium tuberculosis of any site, pulmonary,
disseminated, extrapulmonary
• Pneumocystis jiroveci pneumonia
• Pneumonia, recurrent
• Progressive multifocal encephalopathy
• Salmonella septicemia, recurrent
• Toxoplasmosis of the brain, onset at age >1mo
• Wasting syndrome, attributed to HIV
DIAGNOSIS
Taking a Sexual History
• The history should be carefully taken to elicit possible
exposures to HIV.
**HIV Patients are very sensitive because they are
undergoing a lot of stress so you must establish rapport to
extract all the information that you need.
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 INTERNAL MEDICINE
• Respect and compassion
• Straightforward and nonjudgmental, with appropriate
counselling regarding risk-taking behavior
• Use open-ended questions
• An assurance of confidentiality
• As part of the clinical encounter, health-care providers
should routinely obtain sexual histories from their
patients
The 5 “Ps”
1. Partners
o Do you have sex with men, women or both?
o In the past 2 mos, how many partners have you had sex
with?
o In the past 12 mos, how many partners have you had sex
with?
o Is it possible that any of your sex partners in the past 12 mos
had sex with someone else while they were still in a sexual
relationship with you?
2. Prevention of Pregnancy
o What are you doing to prevent pregnancy?
3. Protection from STIs
o What do you do to protect yourself from STIs and HIV?
4. Practices 1. Informed Consent
o What kind of sex have you had recently? Vaginal sex, Anal
Sex or oral sex?
o Is condom used?
5. Past History of STIs
o Have you ever had an STI?
o Have any of your partners had an STI?
Additional questions to identify HIV and viral hepatitis risk:
o Have you or any of your partners ever injected drugs?
o Have you or any of your partners exchanged money or drugs
for sex?
Sexual History Taking
• Unprotected sexual intercourse, especially receptive anal
intercourse (8-fold higher risk of transmission)
• A large number of sexual partners
• Prior or current sexually transmitted diseases (STDs):
Gonorrhea and chlamydia infections increase the HIV 2. HIV Screening
transmission risk 3-fold, syphilis raises the transmission
risk 7-fold, and herpes genitalis raises the transmission 3. Pre-HIV Test Counselling
risk up to 25-fold during an outbreak
• Sharing of intravenous drug paraphernalia
• Receipt of blood products (before 1985 in the United 4. Conduct of HIV Testing
States) 5. Post-HIV Test Counselling
• Mucosal contact with infected blood or needle-stick
injuries
• Maternal HIV infection (for newborns, infants, and
children): Steps taken to reduce the risk of transmission at
birth include cesarean delivery and prenatal antiretroviral
therapy in the mother and antiretroviral therapy in the
newborn immediately after birth.
HIV Testing
• HIV testing shall be routinely offered, prioritized for,
and promoted to the following:
o Key populations including adolescents:
▪ Key Population: members of this
population are male who are having sex
with male, people in prisons and other
closed settings, people who inject drugs,
sex workers, and transgender men and
women.
o High risk individuals who have not been tested recently
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HUMAN IMMUNODEFICIENCY VIRUS (HIV)
o Partners, infants and children of PLHIV
o Patients showing signs and symptoms consistent with
AIDS defining illness
o Patients with Sexually Transmitted Infections
o Patients with Hepatitis B and C
o Patients with under nutrition not responsive to
interventions
o All confirmed tuberculosis patients
o All pregnant women regardless of risk
Conduct of HIV Testing
• Verbal consent: for >18y/o only in community-based HIV
screening services
• Written consent: all 15 y/o and above
o For infants/children born to HIV positive mothers,
persons below 15 years old needing HIV test, and
patients who are comatose or mentally
incapacitated, consent for HIV test shall be provided
by the nearest of kin;
o In addressing serious cases, that deem HIV test to
be a crucial diagnostic test to proceed with clinical
management, consent for HIV test can be provided
by a licensed social worker for minors, mentally
incapacitated, and comatose patients only if
consent from parent or nearest of kin cannot be
obtained
• Using Rapid Diagnostic Tests
• Provided by HIV counsellor
• Emphasize confidentiality
Types of HIV test
• Nucleic Acid Test (NAT)
o Test for the actual virus and how much virus in the
blood (known as Viral load test)
o Detect HIV sooner but very expensive and not
routinely used for screening
o Includes HIV RNA/DNA PCR
• Antigen/Antibody Test
o Antibodies are produced by immune system when
exposed to HIV
o Antigen p24 is produced even before antibodies
develop
• Antibody Tests
o Only test for antibodies
• It is strongly recommended that HIV virologic testing be
used to diagnose HIV infection in infants and children
below 18 months of age (strong recommendation, high-
quality evidence)
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 INTERNAL MEDICINE
• Since all infants born to HIV-infected mothers have a
positive antibody test at birth because of the passive
transfer of the HIV antibody across the placenta,
virological testing is used to confirm the diagnosis.
• For infants born to HIV-infected mothers, viral diagnostic
testing is usually performed within the first 2 days of
life, at 1 to 2 months of age, and at 4 to 6 months of age.
A diagnosis of HIV infection can be made with two positive
virologic tests obtained from different blood samples.
Diagnosis of HIV Infection <18 mos of age
• HIV DNA PCR
o Historically preferred test to diagnose HIV-1
subtype B infection in infants and children younger
than 24 mo of age; highly sensitive and specific by 2
wk of age and available; performed on peripheral
blood mononuclear cells.
o False negatives can theoretically occur in non-B
subtype HIV-1 infections.
o Historically had been preferred for testing in young
infants.
• HIV RNA PCR
o Preferred test to identify non-B subtype HIV-1
infections
o Similar sensitivity and specificity to HIV DNA PCR in
infants and children younger than 24 mo of age
Time to positivity of HIV diagnostic tests
Fig. 5 Time to positivity of HIV diagnostic tests
❖ Fourth generation is now the recommended test among
other Enzyme-linked immunoassay generations:
o Antigen + antibody
o 15 to 20 days only
❖ Western blot
o Although a confirmatory test, it takes a while
before diagnosis, it is now rarely used.
❖ HIV Viral load test
o Can detect as early as 5 days, but very costly
Diagnostic Algorithm of HIV
WHO recommends the following in developing an algorithm:
o Recommendation 1: HIV testing services may use
combinations of RDTs or combinations of RDTs/enzyme
immunoassays (ElAs)/supplemental assays rather than
EIA/Western blot combinations.
o Recommendation 2: Three different serological assays
that do not share the same false reactivity must be
included in the algorithm.
o Recommendation 3: Among the serological assays, first
test must be the most sensitive of the three. Succeeding
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HUMAN IMMUNODEFICIENCY VIRUS (HIV)
tests, on the other hand, must have superior diagnostic
specificity.
**See Appendices for the Diagnostic Algorithm of HIV
Post-HIV Test Counselling
HIV Test Non-Reactive Result
• Provide the patient official copy of the HIV non-reactive
test
• Explain that either the patient may either be non-infected
or may have been infected from the most recent exposure
but his/her body has not produced sufficient level of
antibodies that can be detected by HIV test kit
• Check for latest or ongoing significant risk if there is, the
counsellor shall:
o Emphasize the importance of knowing the HIV
status of sexual partners and recommend HIV
testing.
o Facilitate risk reduction planning, discuss
prevention of HIV infection and the importance
of maintaining an HIV negative status
o Offer retesting after 6 weeks from the last HIV
test result
o Refer the patient for continuous support, STI and
HIV prevention services and other appropriate
services from partner community-based
organizations
Frequency of retesting shall be recommended to the following:
Population Frequency
1. Key Population Every 3 months
2. Pregnant Women who 1st trimester
belong to key 2nd trimester
populations or a 3rd trimester
partner of a PLHIV And at least once while
(Person Living with breastfeeding
HIV)
3. Casual or intimate Annual
partners of key
populations or PLHIV
HIV Test Reactive Result
• Patient shall be verbally informed of the reactive result.
• No written results shall be given to patient.
• Reactive blood samples shall be sent for confirmatory
testing to NRL-SLH/SACCL or its designated Confirmatory
rHIVda site.
The HIV Counselor shall do the following:
1) Help the patient cope with emotions arising from the test
result;
2) Address significant concerns and assist the patient to
identify who in her/his network may be available and
acceptable to offer immediate support;
3) Reinforce risk reduction planning and other procedures
4) Discuss importance of disclosure of her/his HIV status to
partner(s), family member(s) and/or significant other(s).
Help the client in a decision-making process to facilitate
disclosure by presenting different strategies to do so.
5) Encourage and offer referral for counseling and testing of
partners and children;
6) Assess the risk of violence or suicide and discuss possible
steps to ensure the physical safety of the patient;
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 INTERNAL MEDICINE HUMAN IMMUNODEFICIENCY VIRUS (HIV)

7) Inform the patient of the importance of/or offer early • Etravirine

treatment in maintaining health and transmission • Nevirapine
prevention and management of possible opportunistic • Rilpivirine
infections.
8) Provide the patient a referral letter and ensure that the Protease Inhibitors
patient shall be linked to the treatment hub or primary MOA: Block new HIV from becoming mature HIV
HIV care clinic of his/her choice for access of antiretroviral • Atazanavir
therapy, management of possible opportunistic infections, • Darunavir
care and support services.
• Fosamprenavir
• Indinavir
Laboratory tests during initial patient visits • Nelfnavir
To stage HIV disease and to assist in the selection of ARV drug • Ritonavir
regimens:
• Saquinavir
✓ HIV antibody testing (if prior documentation is not
• Tipranavir
available or if HIV RNA is below the assay's limit of
detection)
✓ CD4 T lymphocyte cell count (CD4 count) Fusion Inhibitors
✓ Plasma HIV RNA (viral load) MOA: Blocks HIV envelope from fusing with CD4 cell membrane
✓ Complete blood count, chemistry profile, transaminase • Enfuvirtide
levels, blood urea nitrogen (BUN), and creatinine,
urinalysis, and serologies for hepatitis A, B, and C viruses Entry (Attachment) Inhibitors
✓ Fasting blood glucose and serum lipids MOA: CCR5 (Co-receptor) Antagonist
✓ Genotypic resistance testing • Maraviroc
• For patients who have HIV RNA levels <500 to 1,000
copies/mL, viral amplification for resistance testing may Integrase Inhibitors
not always be successful MOA: Prevent HIV DNA from integrating to the Host DNA
• Dolutegravir
ANTIRETROVIRAL THERAPY • Raltegravir
Readiness to start ART
• Before initiation of therapy, adolescents' readiness and Anti-Viral Regimen
ability to adhere to therapy within their psychosocial
context need to be carefully considered as part of ARV Regimen for HIV-infected Adults and
therapeutic decision making Adolescents >10 years old
• Once ART is initiated, appropriate support is essential
to reduce potential barriers to adherence and maximize FIRST LINE REGIMEN: 2NRTI + 1NNRTI
the likelihood of achieving sustained viral suppression • Preferred 1st line NRTI: Tenofovir (TDF) + Lamivudine
(3TC)
Anti-Viral Drugs • Alternative 1st line NRTI: Abacavir (ABC) + 3TC
❖ We need multiple drugs to prevent resistance. However, • ABC is preferred over TDF for patients with estimated
the challenge now is there have been recent reports of Creatinine clearance of <60ml/min.
developing drug resistance due to long-term use. • 1st line NNRTI: Efavirenz (EFV)
• Start antiretroviral therapy (HAART) in all patients • Alternative NNRTI: (Rilpivirine) RPV, that may only be
regardless of clinical stage initiated for asymptomatic patients >12 y/o with known
• Goals of HAART: Maximal suppression of HIV RNA CD4 >350cells/mm3, non-pregnant and not on
1. Reduce HIV-related morbidity and mortality Rifampicin-containing regimen; Contraindicated among
2. Prevent transmission of HIV to others patients taking antacids, H2 blockers/PPIs.
**See Appendices for The HIV Life Cycle
SECOND LINE REGIMEN: 2NRTI + boosted Pls
Nucleoside/Nucleotide Reverse Transcriptase • Preferred 2nd line: 2 NRTI + Lopinavir/ritonavir (LPV/r)
Inhibitors • Zidovudine (AZT) + 3TC + LPV/r if previously on TDF or
MOA: Block the conversion of HIV RNA to HIV DNA ABC
• Abacavir • TDF or ABC + 3TC + LPV/r if previously on AZT
• Didanosine • Alternative second line: 2NRTI + DRV + RTV
• Emtricitabine • AZT + 3TC + Darunavir (DRV) + RTV if previously on TDF
• Lamivudine or ABC
• Stavudine • TDF or ABC + 3TC + DRV + RTV if previously on AZT
**Note:
• Tenofovir
• TFD - Tenofovir
• Zidovudine
• 3TC – Lamivudine
Non-Nucleoside Reverse Transcriptase Inhibitors • ABC – Abacavir
MOA: Block the conversion of HIV RNA to HIV DNA • RPV – Rilpivirine
• Delavirdine • LPV/r – Lopinavir/ritonavir
• Efavirenz • AZT (ZDV) - Zidovudine

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 INTERNAL MEDICINE HUMAN IMMUNODEFICIENCY VIRUS (HIV)

• DRV – Darunavir 2. Treating those living with HIV differently can negatively
• RTV – Ritonavir affect their ability to secure life’s necessities, like housing,
employment, and medical care
ARV Regimen for HIV-infected 3 years to <10 years
old

FIRST LINE REGIMEN: 2NRTI + 1NNRTI

• Preferred 1st line NRTI: Abacavir (ABC) + Lamivudine
(3TC)
• Alternative 1st line NRTI: Zidovudine (AZT) + Lamivudine
(3TC) or Tenofovir (TDF) + 3TC (TDF preferred over AZT
for children with Hgb <10g/L
• 1st line NNRTI: Efavirenz (EFV)
Guide Questions
• Alternative 1st line NNRTI: Nevirapine (NVP) 1. This HIV test is to detect how much virus is in the blood:
a. Antigen/Antibody test
ARV Regimen for HIV-infected < 3 years old b. NAT
c. Antigen p24
0-2 weeks 2 weeks – 3 3-36 weeks d. Western Blot
months
Preferred Zidovudine + Abacavir or Abacavir or 2. Viral load is highest during what phase of HIV infection?
Lamivudine + Zidovudine + Zidovudine + a. Acquired Immunodeficiency Syndrome
Nevirapine Lamivudine or Lamivudine or b. Acute HIV infection
Lopinavir/rito Lopinavir/riton c. HIV Dormancy
navir avir d. Clinical Latency

Complications 3. These are factors that increase the risk of HIV infection,
EXCEPT
Monitoring For Complications
a. Alcohol Use
• Non-infectious complications:
b. Previous STI
o Metabolic complications, cardiovascular
c. Men having sex with men
diseases, malignancies d. Undetectable viral load
o Wellness counselling - discussions on nutrition,
exercise and avoidance or cessation of smoking 4. What is the most severe phase of HIV infection where there is
• Infectious complications: consequent depletion of CD4 count?
o Most commonly occur when CD4 count <200 a. Acute phase
cells/Ul b. Latent phase
c. HIV Inactivity
SUPPORT GROUPS d. AIDS
❖ Counselling is the most important thing in managing HIV
patients, we are encouraged to refer them to support 5.First line anti-retroviral therapy for patients 10 y/o with HIV?
groups. a. Tenofovir + Lamivudine + Rilpivirine
• The REDRIBBON Care Management Program b. Abacavir + Lamivudine/Ritonavir
• Loveyourself c. Tenofovir + Lamivudine + Efavirenz
• AIDS Society of the Philippines d. Zidovidine + Lamivudine/Fitonavir
• PAFPI (Positive Action Foundation Philippines, Inc.)
• HASH (HIV & AIDS Support House) 6. What is the mechanism of action of Tenofovir?
a. Block new HIV from becoming mature HIV
Despite the absence of cure, the natural history of the disease was b. Block the conversion of HIV RNA to HIV DNA
radically changed, and now, persons with HIV infection without c. Blocks HIV Envelope from fusing with CD4 cell membrane
significant comorbidities who are treated before significant d. CCR5 (Co-receptor) Antagonist
immunosuppression can expect a life expectancy approaching
that of the general population 7. What is a positive HIV result according to the algorithm by
WHO?
How can we stop HIV Stigma? a. T1+, T2+, T3+
Learn about the Basics About HIV Stigma b. T1+, T2 -
• What is HIV Stigma? c. 2 T1-
d. T1+, T2+, T3-
• Where can I find support?
Answers: B, B, D, D, C, B, A

• How can I educate others about HIV Stigma?

Why stopping HIV Stigma Matters: References:

1. When people are afraid of experiencing discrimination, • Dra. Cuvin’s PPT
they are less likely to be tested or treated for HIV.

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Appendix A. HIV Life Cycle and MOA of HIV Drugs
Appendix B. Rapid HIV Diagnostic Algorithm for the Philippines (rHIVda)

Appendix C. HIV Diagnostic Algorithm for Infants