Official reprint from UpToDate®

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Management of nonoccupational exposures to HIV and

hepatitis B and C in adults
Authors: Judith A Aberg, MD, Demetre C Daskalakis, MD, MPH
Section Editors: John G Bartlett, MD, Paul E Sax, MD
Deputy Editor: Meg Sullivan, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Oct 2019. | This topic last updated: May 24, 2019.

INTRODUCTION

Patients who are potentially exposed to HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV)
through a nonoccupational exposure or injury are at risk for acquiring infection. Patients can be
exposed through sexual contact or through exposure to infected blood (or blood-contaminated body
fluids). Post-exposure prophylaxis for HIV and HBV may reduce the risk of transmission if
administered soon after the exposure.

The management of adults with a potential nonoccupational exposure to HIV, HBV, and HCV are
reviewed here. Detailed discussions of the risk of transmission after exposure to these pathogens,
the management of occupational exposures, and the prevention of mother-to-child transmission are
found elsewhere:

● (See "HIV infection: Risk factors and prevention strategies".)

● (See "Risk of HIV from blood transfusion".)
● (See "Prevention of hepatitis B virus and hepatitis C virus infection among health care
providers".)
● (See "Management of health care personnel exposed to HIV".)
● (See "Antiretroviral and intrapartum management of pregnant HIV-infected women and their
infants in resource-rich settings".)
● (See "Prevention of mother-to-child HIV transmission in resource-limited settings".)
WOUND MANAGEMENT

For patients with a possible exposure to blood or body fluids after a needle-stick injury or a skin or
mucous membrane exposure, it is important to clean the wound. Discussions of wound management
are found elsewhere. (See "Management of health care personnel exposed to HIV", section on 'Initial
actions following exposure' and "Prevention of hepatitis B virus and hepatitis C virus infection among
health care providers", section on 'Wound care'.)

EXPOSURE TO HIV

HIV infection is acquired through sexual contact, exposure to infected blood (including blood-
contaminated body fluids), or perinatal transmission. The distribution of the modes of transmission
of HIV infection varies in different countries. In the United States, male-to-male sexual contact and
injection drug use (IDU) account for more than half of cases [1]. In contrast, in certain resource-
limited areas (eg, Sub-Saharan Africa), penile-vaginal intercourse is responsible for 70 to 80 percent
of HIV infections [2,3].

The risk of HIV infection also varies by the type of sexual or parenteral exposure (table 1). Risk
factors for HIV transmission include a high HIV viral load in the source, the presence or absence of
sexually transmitted infections (STIs), lack of circumcision, and certain host and genetic factors [4-6].
A detailed discussion of HIV transmission is found elsewhere. (See "HIV infection: Risk factors and
prevention strategies", section on 'Risk factors for infection'.)

General principles of HIV post-exposure management — Patients should be evaluated after a

possible exposure to HIV to determine if nonoccupational post-exposure prophylaxis (nPEP) with
antiretroviral therapy (ART) should be offered to reduce the risk of HIV transmission. Although the
data supporting nPEP are limited, feasibility and safety data have led to widespread acceptance of
this practice, which has been advanced by expert guideline committees [7-10]. (See 'Efficacy of post-
exposure prophylaxis' below.)

The decision to initiate nPEP depends upon several factors. These include:

● The risk of HIV acquisition. As an example, a person who engages in condomless receptive anal
sex has a much greater estimated risk of HIV acquisition than a person who has oral sex (table
1).

● The amount of time that has elapsed after exposure, since nPEP should be administered as soon
as possible and within 72 hours. (See 'Timing of HIV prophylaxis' below.)
 ● The potential for drug toxicity. (See 'Antiviral therapy' below.)

● The cost of medications and the need for laboratory and clinical monitoring while taking nPEP.
(See 'Patient monitoring' below.)

Who should receive post-exposure prophylaxis — For patients who present within 72 hours of a
possible HIV exposure, it is important to assess if the exposure presents a substantial risk of HIV
acquisition (algorithm 1). We consider any of the following to be a high-risk exposure:

● Condomless receptive or insertive anal or vaginal intercourse

● A percutaneous exposure to blood (or body fluids contaminated with blood)

For patients who have had a high-risk exposure, we recommend initiating nPEP if the source is HIV-
infected. We also suggest nPEP when the HIV status of the source is unknown if the source is at high
risk for being HIV-infected (eg, man who has sex with men, injection drug user, sex worker), or if the
patient was sexually assaulted. A more detailed discussion of the management of sexual assault
victims is found elsewhere. (See "Evaluation and management of adult and adolescent sexual assault
victims", section on 'Treatment'.)

Some patients may desire nPEP if they had condomless sex with a source whose risk factors are
unknown. For such patients, the decision to initiate nPEP depends upon the patient's exposure risk,
such as the route of exposure (table 1), and other cofactors that heighten risk of transmission (eg,
presence of genital ulcer disease). If the indications for nPEP are unclear, clinicians can call the
National Clinician's Post-Exposure Prophylaxis Hotline at 888-448-4911 for expert advice.

Certain patients repeatedly present with exposures that could qualify for nPEP (eg, discordant sex
partners who rarely use condoms or injection drug users who often share injection equipment). For
such patients, we try to avoid repeated courses of nPEP, and we discuss the possibility of
transitioning from a post-exposure regimen to pre-exposure prophylaxis (PrEP) to reduce the risk of
subsequent HIV infection [8,11]. (See "Patient evaluation and selection for HIV pre-exposure
prophylaxis", section on 'Patients transitioning from post-exposure prophylaxis'.)

Patients who are taking PrEP typically do not require additional post-exposure prophylaxis for HIV,
unless they report taking their medication sporadically or have not taken their PrEP regimen within the
week before the exposure [11]. Another time that nPEP should be considered in patients taking PrEP
is if the source is known to have confirmed drug-resistant virus [8,11]. Specific nPEP regimens are
discussed below. (See 'Special considerations' below.)

For most patients, the duration of nPEP is 28 days. However, if the source is available and agrees to
testing, post-exposure prophylaxis may be able to be discontinued if the HIV RNA is suppressed or if
HIV testing returns negative. (See 'Duration of post-exposure prophylaxis' below.)
Timing of HIV prophylaxis — Nonoccupational post-exposure prophylaxis (nPEP) should be given
within 72 hours of an exposure. Once the need for nPEP has been identified, the patient should
receive an immediate dose. The first dose should not be delayed pending HIV testing of either the
exposed patient or the source. (See 'HIV and other testing' below.)

Animal data suggest that there is a small window of opportunity to interrupt HIV transmission. A
meta-analysis that included data from 25 nonhuman primate studies found a significant association
between timing of post-exposure prophylaxis and reduced seroconversion after exposure to a closely
related virus, simian immunodeficiency virus (SIV) [12]. In an early study of 24 macaques who
received post-exposure prophylaxis with an experimental nucleoside analog, there was no evidence of
viral replication if treatment was started within 24 hours of exposure; however, the efficacy of post-
exposure prophylaxis decreased when the time between exposure and treatment was extended [13].

Antiviral therapy

Choice of regimen — We administer a three-drug regimen for nPEP given the efficacy of this
combination in patients with chronic HIV infection, the improved tolerability of available treatment
regimens, and the demonstrated safety of these agents. This approach is consistent with several
guideline panels, including the United States Centers for Disease Control and Prevention (CDC), the
United States Public Health Service, the International Antiviral Society-USA Panel, and the World
Health Organization [7,8,14,15].

Several possible regimens can be used for nPEP (table 2). For most patients, we suggest:

● Tenofovir disoproxil fumarate-emtricitabine (TDF/FTC)

PLUS

● An integrase strand transfer inhibitor (raltegravir or dolutegravir)

For many patients, dolutegravir is the preferred integrase strand transfer inhibitor because it is
administered as one pill once daily; in addition, it may be particularly effective if there is concern for
transmission of drug-resistant virus. (See 'Special considerations' below.)

However, dolutegravir should be avoided in the following groups:

● Persons of childbearing potential who are sexually active or have been sexually assaulted and
who are not using an effective birth control method (eg, intrauterine contraception, injectable or
oral contraception). (See "Contraceptive counseling and selection for women".)

● Persons early in pregnancy (eg, eight weeks since last menstrual period)
More detailed information on the choice of regimen in this patient-group and other select populations
is discussed below. (See 'Special considerations' below.)

Alternative regimens use TDF/FTC in combination with a pharmacologically boosted protease

inhibitor (PI) (eg, boosted darunavir). However, compared with the preferred regimens, there is an
increased risk of drug interactions when a pharmacologic-boosting agent (ie, cobicistat or ritonavir) is
used. Information about specific drug interactions can be found in the Lexicomp drug interaction
program within UpToDate.

There are insufficient data to support the use of tenofovir alafenamide (TAF) in place of tenofovir
disoproxil fumarate (TDF) for nPEP. This newer form of tenofovir has less bone and renal toxicity
compared with TDF and is effective in suppressing HIV RNA when used as part of a combination
regimen for HIV-infected patients [16]. However, TAF results in lower mucosal tenofovir levels
compared with TDF and may, therefore, be less effective in preventing HIV transmission [17,18].
Although studies evaluating the use of TAF for nPEP are unlikely, a study evaluating TAF for PrEP is
ongoing. (See "Administration of pre-exposure prophylaxis against HIV infection".)

Special considerations — When choosing a regimen, special considerations include:

● If the source is HIV infected – We prefer a regimen that uses dolutegravir or a boosted PI (eg,
darunavir) as the third agent if the source is known to be HIV infected and there are concerns for
drug-resistant virus (eg, the patient has failed multiple regimens or does not take their
antiretroviral medications as prescribed). Resistance to either dolutegravir or darunavir is
uncommon. The decision to initiate dolutegravir versus a boosted PI depends upon patient-level
factors (eg, dolutegravir should be avoided in persons of childbearing potential who are not on
effective contraceptives) and the source's ART history, if known. The initial regimen can be
modified based upon the results of drug resistance testing, should they become available.

● Reduced kidney function – For individuals with reduced kidney function (estimated glomerular
filtration rate <60 mL/min), we initiate TDF plus FTC at doses adjusted according to the patient's
renal function. Refer to the Lexicomp drug information topics within UpToDate for specific
dosing recommendations.

Some experts prefer to avoid TDF for nPEP in patients with reduced kidney function given
concerns for renal toxicity [8]. However, the nephrotoxicity associated with TDF typically occurs
with long-term administration, and we feel alternative NRTI combinations (eg, zidovudine-
lamivudine) are associated with reduced tolerability and even greater toxicity (eg, anemia). If
there are concerns about the continued use of a tenofovir-containing regimen in the setting of
reduced kidney function, it may be reasonable to transition the patient to abacavir-lamivudine, if
testing for HLA-B*57:01 is negative. (See "Abacavir hypersensitivity reaction".)
 ● Persons of childbearing potential/persons who are pregnant – Our preferred nPEP regimen for
persons who are or could become pregnant is TDF/FTC plus raltegravir (400 mg twice daily). On
May 18, 2018, the US Food and Drug Administration (FDA) released a safety alert regarding the
use of dolutegravir in all persons who are able to become pregnant [19]. This was issued in
response to a preliminary report suggesting an increased rate of neural tube defects in infants
born to women in Botswana who received dolutegravir at the time of conception [20,21]. The risk
of a fetus developing a neural tube defect is during the first 28 days.

It is unknown whether other integrase strand inhibitors share the potential risk of neural tube
defects seen with dolutegravir; however, raltegravir has been extensively used in pregnant
women and individuals of childbearing potential for at least a decade without any evidence of
risk to the fetus. Nevertheless, this uncertainty should be discussed with patients planning to
initiate raltegravir. A ritonavir-boosted PI (eg, boosted darunavir) is a suitable alternative third
agent.

If dolutegravir is still being considered and the patient was not using effective birth control at the
time of exposure, a pregnancy test should first be obtained. If the test is positive or if the patient
desires pregnancy, raltegravir or a ritonavir-boosted PI should be used as the third agent in
combination with TDF/FTC. If the test is negative and the patient does not desire pregnancy, the
patient can take dolutegravir but should use an effective contraception method until the nPEP
regimen is completed.

Persons who are pregnant and persons of childbearing potential who are not on effective
contraception should also avoid elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil
fumarate and other cobicistat-containing regimens due to decreased drug levels during
pregnancy (table 2). In addition, bictegravir should be avoided because it is structurally similar to
dolutegravir and is coformulated with TAF, which we do not use for nPEP.

A detailed discussion of the dosing and safety of antiretroviral agents in persons of childbearing
potential and during pregnancy is found elsewhere. (See "HIV and women" and "Safety and
dosing of antiretroviral medications in pregnancy".)

Rationale — There are limited data on the relative efficacy of nPEP regimens. (See 'Efficacy of post-
exposure prophylaxis' below.)

Selected medications are chosen based upon side effect profiles, patient convenience (eg, pill burden
and dosing frequencies), penetration into the genital compartment [22-24], and completion rates [25-
27]. As examples:
● Using tenofovir-emtricitabine as the NRTI combination – There has been extensive use of
coformulated tenofovir disoproxil fumarate-emtricitabine as the NRTI combination because it is
well tolerated and requires once-daily dosing. In addition, there is excellent accumulation of
these agents in the genital tract [23]. The main concerns with the use of tenofovir disoproxil
fumarate-emtricitabine are renal toxicity and bone loss attributable to TDF. Patients are more
likely to develop Fanconi syndrome if they have reduced kidney function and/or a PI is used as
the third agent. However, these adverse effects usually occur with long-term administration of
TDF, and not the short duration used for nPEP.

Abacavir-lamivudine (coformulated as Epzicom) should not be used as part of an initial nPEP

regimen since rapid initiation of therapy is not possible. Patients must be screened for the
presence of HLA-B*57:01 before abacavir can be administered since abacavir is associated with
a severe hypersensitivity syndrome in patients who are positive for this allele. (See "Abacavir
hypersensitivity reaction".)

Zidovudine-lamivudine (coformulated as Combivir), which had been the mainstay of nPEP, has
been associated with poor nPEP completion rates [25-27]. In addition to requiring twice-daily
dosing, it is associated with adverse reactions, including significant hematologic toxicity,
headaches, and fatigue. Hence, we do not use this combination for nPEP.

● Using an INSTI for the third agent – For the third agent, we prefer integrase inhibitors because
they are better tolerated and have fewer drug-drug interactions compared with PIs, which had
traditionally been used in nPEP regimens. In addition, small studies have demonstrated that
raltegravir in combination with tenofovir disoproxil fumarate-emtricitabine was well tolerated as
nPEP, except for a few cases where patients developed myalgias and elevation of creatinine
kinase levels [28,29]. Raltegravir also achieves higher concentrations in the male and female
genital tract than PIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs) [30,31].
Guidelines put forth by the CDC include raltegravir as one of their preferred regimen [7,8].

Although most experience with nPEP has been with raltegravir, dolutegravir has the adherence
benefit of once-daily administration. The fixed-dose combination of
elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate can also be administered as a
single-daily tablet; however, there is an increased risk of drug interactions compared with the
other integrase inhibitor regimens because of the boosting agent, cobicistat. The newest
integrase inhibitor, bictegravir, was approved in February 2018. However, this agent is not used
for nPEP since it is only available as a coformulated tablet with tenofovir alafenamide, which we
do not use for nPEP. (See 'Choice of regimen' above.)
 For individuals who are either planning to conceive or are not using effective contraception, we
do not initiate dolutegravir because of concerns about a potential risk of neural tube defects with
dolutegravir exposure at the time of conception. In addition, we do not initiate a cobicistat-
boosted regimen (eg, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate)
because of concerns about adequate levels during pregnancy, or bictegravir because of a similar
chemical structure to dolutegravir. (See 'Special considerations' above.)

The NNRTIs are generally not used for nPEP. Nevirapine has been associated with severe
hepatotoxicity in patients receiving post-exposure prophylaxis and it is contraindicated for this
purpose. Other NNRTIs (eg, rilpivirine, efavirenz) may be suitable third agents, but are limited by
their low barrier to resistance. As an example, the risk of transmitted resistance to efavirenz may
be as high as 20 percent [32]. Although we don't routinely use rilpivirine, it has been studied for
postexposure prophylaxis and is a recommended option in some countries [33].

In addition, efavirenz has significant central nervous system side effects.

A more detailed overview of antiretroviral agents used to treat HIV is found elsewhere. (See "Overview
of antiretroviral agents used to treat HIV" and "Selecting antiretroviral regimens for the treatment-
naïve HIV-infected patient".)

HIV and other testing — In most situations, the HIV status of the exposed patient and source are not
known at the time of presentation. Initial treatment decisions should be made based upon the nature
of the exposure, even in the absence of immediate HIV test results. (See 'Who should receive post-
exposure prophylaxis' above.)

When HIV testing is performed, we prefer a rapid laboratory-based antigen/antibody assay that
detects HIV p24 antigen and HIV antibodies. (See "Screening and diagnostic testing for HIV infection",
section on 'Combination HIV antigen and antibody tests'.)

Determining the HIV status of the exposed person — Rapid HIV testing should be performed on all
persons seeking evaluation after a potential nonoccupational HIV exposure. The preferred three-drug
regimens for nPEP are adequate for both treatment and prevention of HIV, so early initiation of a
three-drug regimen pending lab results is appropriate. (See 'Who should receive post-exposure
prophylaxis' above and 'Antiviral therapy' above.)

Determining the HIV status of the source — If the source is known and is willing, they should be
tested for HIV. In most scenarios, a negative rapid HIV test negates the need for continued nPEP.
However, if there is concern that the source is acutely infected with HIV, additional RNA testing should
be performed since HIV screening tests (eg, antibody/antigen or antibody only) may not detect acute
HIV infection. (See "Acute and early HIV infection: Clinical manifestations and diagnosis".)
If the source is known to be HIV-infected, he or she should be interviewed if possible to determine
their HIV treatment history, and the results of their most recent viral load and resistance tests. In
addition, we repeat an HIV viral load and genotype at time of exposure. This information will provide
guidance regarding the need for continued nPEP and/or which regimen should be administered. (See
'Duration of post-exposure prophylaxis' below and 'Antiviral therapy' above.)

Testing for hepatitis B and C virus — All patients with nonoccupational exposures should be
evaluated for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. If the patient's status is
unknown, we test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc),
hepatitis B surface antibody (anti-HBs), and hepatitis C antibody. If the source's status is unknown,
they should also be tested, if possible [8] (table 3).

It is important to know if the exposed patient has evidence of chronic HBV infection (HBsAg-positive)
since tenofovir and emtricitabine are both active against HBV, and discontinuing nPEP, especially in
patients with cirrhosis, may lead to a flare of their HBV infection. Thus, HBsAg-positive patients
should be evaluated to see if antiviral therapy for HBV should be continued after they have completed
the 28-day course for nPEP. If treatment is discontinued, such patients should be monitored closely.
(See "Hepatitis B virus: Overview of management".)

The results of serologic testing can also be used to guide decisions regarding post-exposure
prophylaxis to prevent HBV transmission, and monitoring for possible HCV infection. Detailed
discussions of HBV and HCV post-exposure management are found below. (See 'Exposure to
hepatitis B virus' below and 'Exposure to hepatitis C virus' below.)

Additional considerations after a sexual exposure — After a high-risk sexual exposure:

● Sexual assault survivors should be empirically treated for STIs without testing. (See "Evaluation
and management of adult and adolescent sexual assault victims".)

● Other patients should be offered testing for other STIs, such as gonorrhea, chlamydia, and
syphilis. Patients receiving nPEP have been found to be at high risk for STIs [34]. A detailed
discussion of screening for STIs (including which sites should be tested) is found elsewhere.
(See "Screening for sexually transmitted infections".)

● Women with child-bearing potential should have pregnancy testing and if negative, emergency
contraception should be offered. (See "Emergency contraception".)

Duration of post-exposure prophylaxis — Although the optimal duration of nPEP is unknown,

guidelines recommend a 28-day course of ART for persons with a significant HIV exposure [8,9,15].

If the source is known and is willing to be tested, nPEP can be discontinued if:
 ● A rapid HIV test (preferably a laboratory-based antigen/antibody test) is negative, unless there is
concern that the source is acutely infected with HIV. (See 'Determining the HIV status of the
source' above and "Acute and early HIV infection: Clinical manifestations and diagnosis".)

● The source is HIV-infected and has a suppressed HIV RNA on ART, since such patients are at
very low risk of transmitting HIV [35-37]. However, certain patients may prefer to continue nPEP,
despite the low risk of transmission. (See "HIV infection: Risk factors and prevention strategies",
section on 'Treatment as prevention'.)

Regimens that use TDF/FTC plus an INSTI have led to greater rates of nPEP completion compared
with older regimens, where toxicity often resulted in treatment discontinuation [25-28,38]. As an
example, in a study of 100 patients using TDF/FTC plus raltegravir for nPEP, 85 percent took all or
most of the nPEP regimen [28]. Although side effects included nausea or vomiting (27 percent),
diarrhea (21 percent), headache (21 percent), and fatigue (14 percent), they were mild and did not
result in drug discontinuation. Side effects were significantly less common and completion rates
were higher than those historically observed on PI-based regimens with zidovudine-lamivudine.

Patient counseling and education — All people taking nPEP should be informed about drug side
effects, drug interactions, proper timing of doses, and the need for monitoring. For most, side effects
include nausea, headache, diarrhea, and myalgias. (See "Selecting antiretroviral regimens for the
treatment-naïve HIV-infected patient".)

Health care personnel also need to be well educated about the factors that influence HIV
transmission so appropriate counseling can take place. After a potential HIV exposure, patients
should be counseled about:

● Acute HIV infection – Individuals should be educated about the signs and symptoms of acute
HIV infection, and they should undergo HIV testing, which includes HIV-1 RNA, if they develop
clinical manifestations consistent with the acute retroviral syndrome. The most common
findings are fever, lymphadenopathy, sore throat, mucocutaneous lesions, myalgia/arthralgia,
diarrhea, headache, nausea/vomiting, and weight loss. The usual time from HIV exposure to the
development of symptoms is two to four weeks. More detailed discussions of the clinical
manifestations and diagnosis of acute HIV are found elsewhere. (See "Acute and early HIV
infection: Clinical manifestations and diagnosis".)

● How to avoid secondary transmission – People potentially exposed to HIV should be advised to:

• Use condoms, or practice sexual abstinence to prevent sexual transmission and to avoid
pregnancy during the follow-up period. This is particularly important during the first 12
weeks after exposure when most HIV-infected persons are expected to seroconvert.
 • Refrain from donating blood, plasma, organs, tissue, or semen. The usual duration for this
precaution is 12 months [39].

In addition, breastfeeding, women in resource-rich settings should discuss the risks and benefits
of continuing breastfeeding. (See "Prevention of HIV transmission during breastfeeding in
resource-limited settings".)

● HIV prevention options – For patients who engage in frequent high-risk behaviors, providers
should discuss HIV prevention strategies (eg, condoms, pre-exposure prophylaxis, substance
abuse treatment) [11,40]. These strategies are reviewed elsewhere. (See "HIV infection: Risk
factors and prevention strategies", section on 'Clinical approach to HIV prevention' and "Patient
evaluation and selection for HIV pre-exposure prophylaxis".)

Patient monitoring — Patients should be monitored while receiving post-exposure prophylaxis to

ensure adherence to the regimen and evaluate for potential toxicity (table 3). Patients who have been
traumatized by a sexual assault should have a follow-up visit within a few days of starting
antiretroviral therapy for a more comprehensive discussion of nPEP [41]. After nPEP is discontinued,
patients should have repeat HIV testing to assess for seroconversion.

● HIV Testing – Baseline and follow-up testing for HIV should be performed to see if
seroconversion occurred (table 3). We prefer HIV testing employing a laboratory-based fourth
generation assay that detects HIV p24 antigen and HIV antibodies; this is in agreement with
recommendations from the CDC [42-44].

• Testing should be performed at four to six weeks and three months after the exposure [8].
Testing should also be performed any time if symptoms suggestive of the acute retroviral
syndrome develop. (See 'Patient counseling and education' above and "Acute and early HIV
infection: Clinical manifestations and diagnosis".)

• In patients who become acutely infected with HCV after exposure, the CDC recommends
that additional HIV testing be performed six months after the exposure [8].

Routine monitoring of HIV RNA in an attempt to detect early infection should generally not be
performed because of the risk of a false positive test result. (See "Screening and diagnostic
testing for HIV infection".)

We do not perform HIV testing (antibody, combination antigen-antibody, or HIV RNA) in

asymptomatic patients during the 28-day period of nPEP therapy; the reasons are as follows:

• Tests for HIV have a "window period" during which time HIV cannot be detected.

• HIV may be suppressed while on post-exposure prophylaxis.

 • Patients may erroneously interpret a negative test during this 28-day nPEP therapy period as
a reason to discontinue the medications before the full course is completed.

● Toxicity – Patients should be educated about potential drug side effects including rash and signs
and symptoms of hepatotoxicity (ie, nausea, vomiting, right upper quadrant pain). Laboratory
monitoring while receiving nPEP is only needed if the patient is receiving zidovudine-lamivudine
as the nucleoside combination (table 3). This includes a complete blood count with differential,
blood urea nitrogen, creatinine, and liver function tests after two weeks of treatment.

On rare occasion, an individual may have difficulty tolerating one of the preferred agents, and a
different regimen must be used (table 2). For patients who experience an adverse reaction to
tenofovir-emtricitabine, abacavir-lamivudine is an option only if testing for HLA-B*57:01 is
negative. (See "Abacavir hypersensitivity reaction", section on 'Screening prior to abacavir
exposure'.)

● Adherence – Regular contact with the patient, either in person or by telephone or email, is
important to help ensure adherence to prophylaxis [45].

Failure of prophylaxis — Patients should be informed that there are instances of nPEP failure [46].
Reasons for failure may include poor adherence to the nPEP regimen, suboptimal treatment
regimens, delays in initiation, or ongoing HIV exposures [47]. In situations where nPEP may fail,
selection of resistant virus by drug exposure is possible. The management of patients with potential
drug-resistant virus is found elsewhere. (See "Evaluation of the treatment-experienced patient failing
HIV therapy" and "Selecting an antiretroviral regimen for treatment-experienced HIV-infected patients
who are failing therapy".)

Additional considerations

● Barriers to post-exposure prophylaxis – Many individuals are not aware of nPEP [45,48-51]. As
an example, in a study conducted from 1999 to 2003, which followed 4295 men who have sex
with men (MSM) from six cities in the United States, 48 percent of participants reported
awareness of nPEP, 2 percent utilized nPEP prior to enrollment, and 6 percent utilized nPEP at
least once during the study [52]. Similarly, in a separate study of 554 MSM surveyed at two New
York City bathhouses from 2006 to 2007, only 36 percent of men were aware of nPEP or pre-
exposure prophylaxis [53]. Less than half of the men reported disclosing MSM behavior to their
primary care provider, and this lack of disclosure likely served as a barrier to nPEP use. However,
awareness and use of nPEP may be increasing [49,50,54,55]. In a survey of MSM in Australia,
awareness of nPEP increased from 23 percent in 2001 to 64 percent in 2010 [54].
Nonoccupational post-exposure prophylaxis use also increased from 2.3 percent to 3.9 percent
over that time period.
 Provider-level factors can also be a barrier to nPEP. As an example, patients with high-risk
exposures seen in an emergency departments are not always offered nPEP and many persons
continue to decline nPEP when offered [48]. In a prospective study of 386 adolescent sexual
assault victims in Canada, only 43 percent accepted and one-third completed the 28-day course
of nPEP [56]. One of the major factors associated with nPEP acceptance was the strength of the
recommendation by the examining health care provider. In another study of providers in Miami
and the District of Columbia, the availability of a written nPEP protocol and patient requests for
nPEP were associated with nPEP administration [57].

Another potential barrier is the lack of access to antiretroviral medications. A 2007 survey in Los
Angeles revealed that only 15 percent of health care venues were able to offer nPEP services,
and only 9 percent of these venues were able to provide nPEP to noninsured persons [58].
Although most insurance carriers will pay for nPEP medications, delays with prior authorizations
and mail order pharmacies may further complicate the timeliness of medication initiation.

● Cost-effectiveness – One issue that is specific to nPEP is cost. However, one review concluded
that post-exposure prophylaxis following nonoccupational exposure to HIV on a one-time basis
was cost-effective for the following persons [25]:

• Men who have unprotected receptive anal intercourse with men, whether the source partner
is known to be HIV-positive or not.

• Heterosexuals after unprotected receptive anal intercourse.

• Intravenous drug users sharing needles with a known HIV-positive person.

● Increased behavioral risk – Conflicting data have been published as to whether nPEP may lead
to an increase in high-risk sexual behaviors [22,48,59,60]. As an example, in a study of 397 adults
who received nPEP for high-risk sexual or drug-use exposures, most participants (73 percent)
reported a decrease in high-risk sexual acts within the subsequent 12 months, while only14
percent reported an increase [61].

Efficacy of post-exposure prophylaxis — Post-exposure prophylaxis was first evaluated in pregnant

women to decrease the risk of mother-to-child transmission (MTCT) and in health care personnel who
had accidental needlestick exposures [62-65]. Among such patients, post-exposure prophylaxis with
zidovudine alone reduced transmission by 70 to 80 percent. Although there are major differences
between nonoccupational and occupational exposures (eg, type of exposure, delay in initiating
treatment), post-exposure prophylaxis continues to be recommended by many experts after a high-
risk exposure [8,9,15,38,66-69].
Placebo-controlled clinical trials of post-exposure prophylaxis for nonoccupational HIV exposures
have not been performed [70]. Thus, the data supporting the efficacy of ART for nPEP is limited to
animal studies and observational data [25-28,45,59,71]. Observational studies of patients who were
offered nPEP for HIV prevention after sexual exposure suggested possible benefit, although
conclusions are limited because of the design of the studies and sample sizes have been too small to
be conclusive. As examples:

● In a study of 200 MSM and bisexual men, a supply of nPEP (zidovudine and lamivudine) was
given to all study participants with instructions to take the medications within 96 hours of a self-
identified high-risk exposure [59]. Approximately one-third of the participants took nPEP. Over a
median of 24 months, there were 11 HIV seroconversions (10 among non-nPEP users and 1 on
nPEP). The most common reason for not taking nPEP after a high-risk exposure was sex with a
steady partner.

● A trial to assess the feasibility of offering individualized nPEP was conducted in San Francisco
among 401 persons with eligible sexual and injection drug-use exposures [45]. No
seroconversions were observed among those who completed nPEP (n = 309), those who
interrupted nPEP (n = 37), or those who decided not to take nPEP at all (n = 55). Among sexual
exposures, receptive or insertive anal intercourse was the most common sexual exposure. Of
those who did consent to take nPEP, 97 percent of participants were treated with dual nucleoside
reverse transcriptase inhibitors and 78 percent completed the four-week treatment. Side effects
were not reported.

● In a retrospective study from Amsterdam, a higher incidence of HIV was observed in 355 MSM
who used nPEP (zidovudine-lamivudine plus nelfinavir or atazanavir without ritonavir) than in 728
who did not (6.4 versus 1.6 seroconversions per 100 person years) [25]. The higher incidence of
seroconversion in those who were prescribed and used post-exposure prophylaxis may reflect
higher risk behavior in that group. Of note, 8 of the 11 nPEP users who were infected with HIV
seroconverted more than three months following nPEP use, suggesting that their infections were
not related to nPEP failure, but continued high-risk exposure. The use of an nPEP regimen not
widely prescribed in the US is an additional limitation of this study.

EXPOSURE TO HEPATITIS B VIRUS

Most adults who acquire hepatitis B virus (HBV) do so through sexual or percutaneous exposures.
Transmission between sexual partners ranges from 18 to 44 percent. The risk of acquiring HBV
through a percutaneous exposure has been reported to be approximately 30 percent if the source has
chronic HBV [72]. Additional discussions of HBV transmission are found elsewhere. (See
"Epidemiology, transmission, and prevention of hepatitis B virus infection", section on 'Transmission
of HBV' and "Prevention of hepatitis B virus and hepatitis C virus infection among health care
providers", section on 'Risk of acquisition following exposure'.)

Initial evaluation — After a percutaneous (eg, bite or needlestick) or mucosal exposure to blood or

infectious secretions (eg, semen or body fluids that contain blood), it is important that any wounds be
cleaned. (See 'Wound management' above.)

Such patients should then be evaluated for post-exposure prophylaxis (algorithm 2). If the HBV status
of the exposed patient or source is unknown, we do not delay initial decisions regarding prophylaxis
pending the results of serologic testing. (See 'Approach to prophylaxis' below.)

However, during the initial evaluation of the exposed patient, we obtain laboratory testing for hepatitis
B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), and hepatitis B surface antigen
(HBsAg) to guide future treatment decisions. If the exposed patient requires hepatitis B immune
globulin (HBIG) for prophylaxis (table 4), this testing should be performed before HBIG is
administered. If the source's HBV status is unknown, and he/she is available and willing to be tested,
the same serologic testing should also be performed. (See "Hepatitis B virus: Screening and
diagnosis".)

Post-exposure prophylaxis — The use of post-exposure prophylaxis with hepatitis B vaccine and/or

HBIG can reduce HBV transmission by 70 to 90 percent after an exposure to a patient with chronic
HBV when administered within 12 to 24 hours of an exposure. These findings are based primarily
upon studies evaluating the use of post-exposure prophylaxis to prevent perinatal transmission of
HBV to infants from mothers who are HBsAg-positive. Data supporting the use of post-exposure
prophylaxis to prevent mother-to-child transmission is presented elsewhere. (See "Hepatitis B and
pregnancy", section on 'Mother-to-child transmission' and "Hepatitis B virus immunization in infants,
children, and adolescents".)

Indications — Post-exposure prophylaxis should be administered to patients without previously

documented HBV immunity who are exposed to blood or body fluids from a source who is HBsAg-
positive or whose HBV status is unknown (ie, HBV-unknown). The approach to prophylaxis depends
primarily upon the vaccination history of the exposed patient and the HBV status of the source (if
available) (table 4 and algorithm 2). (See 'Approach to prophylaxis' below.)

Post-exposure prophylaxis should not be delayed pending the results of serologic testing. However, if
prior test results are available at the time of the initial evaluation, the following groups of patients do
not require post-exposure prophylaxis (regardless of the HBV status of the source):
 ● Patients with a known history of recovery from HBV infection (anti-HBs and anti-HBc-positive).
However, individuals with isolated anti-HBc positivity, with both anti-HBs and HBsAg results that
are negative, should receive prophylaxis as if they do not have evidence of immunity. (See
"Hepatitis B virus: Screening and diagnosis", section on 'Isolated anti-HBc' and 'Approach to
prophylaxis' below.)

● Patients who were previously vaccinated and are known to have responded to vaccine (ie, a post-
vaccination anti-HBs ≥10 milli-international units/mL), regardless of when they were vaccinated.
For such patients, testing to confirm the continued presence of antibody is not needed, as
vaccine responders should have lifelong protection even if their antibody level has subsequently
declined.

● Patients with chronic HBV infection (HBsAg-positive).

In addition, immediate prophylaxis is not needed if, at the time of exposure, the source has
documentation of a prior anti-HBs level ≥10 milli-international units/mL after vaccination, or resolved
HBV infection (anti-HBs and anti-HBc). In this situation, exposed patients without evidence of
immunity (eg, those who were never vaccinated) should still receive the hepatitis B vaccine series to
reduce the risk of future HBV transmission. (See "Hepatitis B virus immunization in adults".)

Approach to prophylaxis

Overview — Most patients who require post-exposure prophylaxis should receive the hepatitis B
vaccine if they were exposed to a source who is HBsAg-positive or HBV-unknown. However, there is
no role for additional doses of the hepatitis B vaccine if the exposed patient previously failed to
respond to two complete courses of the hepatitis B vaccine series. (See 'Patients who are vaccine
nonresponders' below.)

HBIG should be administered (in addition to the hepatitis B vaccine), to patients who are without
evidence of immunity if the source is HBsAg-positive. We also administer HBIG to exposed patients
without evidence of immunity if the source is HBV-unknown (table 4), although, the decision to use of
HBIG when the source is HBV-unknown is less clear since there are no data to guide treatment
decisions and guideline recommendations vary [73-75].

Our approach is consistent with the United States Centers for Disease Control and Prevention
guidelines for occupational HBV post-exposure prophylaxis [73,76]. Other guidelines do not routinely
use this approach for nonoccupational exposures and typically recommend HBIG for HBV post-
exposure prophylaxis only if the source is known to be HBsAg-positive [76], or if the source is at high
risk for being HBsAg-positive (eg, injection drug users, sexually active men who have sex with men)
[75]. (See "Prevention of hepatitis B virus and hepatitis C virus infection among health care
providers".)

The use of prophylaxis in selected patient populations is described below. (See 'Patients not fully
vaccinated' below and 'Patients vaccinated but response unknown' below and 'Patients who are
vaccine nonresponders' below.)

Timing — When post-exposure prophylaxis is indicated, it should be administered within 24

hours of an exposure, if possible. If prophylaxis is not available at the initial visit, the exposed patient
should receive the hepatitis B vaccine as soon as possible. HBIG, if indicated, may be more difficult to
obtain, and should be administered within seven days of a percutaneous exposure or 14 days of a
sexual exposure.

Patients not fully vaccinated — Patients without a history of HBV who have not received or
completed their hepatitis B vaccine series require post-exposure prophylaxis after a potential
exposure to a source who is HBsAg-positive or HBV-unknown.

Such patients should receive the hepatitis B vaccine and HBIG. The vaccine and HBIG can be given
simultaneously but should be administered at different sites (table 4).

The patient should then complete the hepatitis B vaccine series, even if the source is found to be
HBsAg negative; the dosing schedule depends upon the type of vaccine (table 5). Such patients
should be tested for anti-HBs one month after completing the hepatitis B vaccine series. Follow-up
testing to assess for HBV transmission is discussed below. (See 'Follow-up testing' below.)

Patients vaccinated but response unknown — Many patients will have completed the initial
hepatitis B vaccine series but do not know if they have had an adequate response (ie, a post-
vaccination anti-HBs ≥10 milli-international units/mL). If the exposed patient is uncertain that they
completed the hepatitis B vaccine series, they should be treated as if they are unvaccinated. (See
'Patients not fully vaccinated' above.)

Patients with an unknown response should receive a booster dose of the hepatitis B vaccine after
exposure to a source who is HBsAg-positive or HBV-unknown (table 4). Further management
depends upon the results of the baseline serologic tests. (See 'Initial evaluation' above.)

● If the anti-HBs is ≥10 milli-international units/mL, no further intervention is needed.

● If the anti-HBs is <10 milli-international units/mL at the time of exposure, then we use the
following approach:

• Source HBsAg positive or HBV unknown – If the source was available for testing at the time
of exposure and the HBsAg returns positive, or if the HBV status of the source remains
 unknown, the exposed patient should receive a dose of HBIG within seven days of a
percutaneous exposure or 14 days of a sexual exposure.

- If the exposed patient had an anti-HBs <10 milli-international units/mL after receiving
only one prior course of the hepatitis B vaccine series, a second hepatitis B vaccine
series should be completed and the anti-HBs should be checked one month after.

- If the exposed patient had an anti-HBs<10 milli-international units/mL after completing

two courses of the hepatitis B vaccine series, there is no role for additional hepatitis B
vaccination. Instead, such patients should receive a second dose of HBIG one month
later. (See 'Patients who are vaccine nonresponders' below.)

Follow-up testing to assess for HBV transmission is discussed below. (See 'Follow-up
testing' below.)

• Source HBsAg negative – In most cases, if the source was available for testing at the time
of exposure and the HBsAg returns negative, the patient can have the anti-HBs repeated
approximately one month after the booster dose. If the anti-HBs is still <10 milli-international
units/mL, the hepatitis B vaccine series should be completed, and the anti-HBs checked one
month after.

However, on rare occasion, the source may be HBsAg negative and anti-HBs negative, but
the anti-HBc returns positive. In this setting, the source should be further evaluated for
evidence of occult HBV infection. (See 'Special considerations if the source has isolated
anti-HBc' below.)

Patients who are vaccine nonresponders — At the time of exposure, some patients know that
they did not respond to the hepatitis B vaccine series (ie, anti-HBs <10 milli-international units/mL).
After an exposure to a source who is HBsAg positive or HBV unknown, the type of prophylaxis
depends upon the number of hepatitis B vaccine doses the exposed patient received (table 4).

● Nonresponders after the initial vaccine series – Patients who did not respond to the initial
hepatitis B vaccine series should:

• Initiate a second course of the hepatitis B vaccine series within 24 hours of exposure. If the
second course had already been started, it should be completed as scheduled (table 5). Anti-
HBs should be measured approximately one month after receiving the last dose of the
vaccine series.

• In addition, such patients should receive a single dose of HBIG at the time of exposure. The
hepatitis B vaccine and HBIG can be given simultaneously but should be administered at
 different sites. Additional information regarding HBIG is described above. (See 'Timing'
above.)

● Nonresponders after two vaccine series – There is no role for additional hepatitis B vaccination
for patients who are nonresponders after receiving two courses of the hepatitis B vaccine series.
Instead, such patients should receive two doses of HBIG given one month apart. Follow-up
testing to assess for transmission is discussed below. (See 'Follow-up testing' below.)

If the source is available for testing and the HBsAg returns negative, the second dose of HBIG is
not needed unless there is evidence of occult infection (ie, isolated anti-HBc and detectable HBV
DNA). (See 'Special considerations if the source has isolated anti-HBc' below.)

Special considerations if the source has isolated anti-HBc — On rare occasions, testing of the
source may reveal that an individual has isolated anti-HBc (HBsAg negative, anti-HBs negative, but
anti-HBc positive). Isolated detection of anti-HBc can occur in several settings: during the window
period of acute hepatitis B (when the anti-HBc is predominantly IgM class); many years after recovery
from acute hepatitis B when anti-HBs has fallen to undetectable levels; and after many years of
chronic HBV infection when the HBsAg titer has decreased below the cutoff level for detection. A
false-positive anti-HBc can also be seen. (See "Hepatitis B virus: Screening and diagnosis", section on
'Isolated anti-HBc'.)

If the source is found to have isolated anti-HBc, additional testing for HBV DNA should be performed
to evaluate for occult HBV infection. This testing does not impact the need for hepatitis B
immunization in nonimmune patients. However, if HBV DNA is detected (or if HBV DNA cannot be
obtained within seven days of a percutaneous exposure or 14 days of a sexual exposure), the
exposed patient should be managed the same way as if the source is HBsAg positive. (See 'Patients
vaccinated but response unknown' above and 'Patients who are vaccine nonresponders' above.)

Follow-up testing — For patients who receive post-exposure prophylaxis for HBV, we perform
testing for anti-HBc and HBsAg after six months to assess for HBV acquisition. Testing should be
done sooner if the patient develops signs or symptoms of hepatitis. (See "Hepatitis B virus: Clinical
manifestations and natural history".)

EXPOSURE TO HEPATITIS C VIRUS

Most patients infected with hepatitis C virus (HCV) in the United States and Europe acquire the
disease through parenteral exposure (eg, intravenous drug use). Although the risk of sexual
transmission appears to be low, among men who have sex with men (MSM), certain sexual practices
may carry a higher risk of transmission [77,78]. As an example, in a study of 5310 MSM followed for a
median of seven years, unprotected receptive anal sex with more than one partner was independently
associated with incident HCV infection among both HIV-infected and uninfected participants,
whereas unprotected insertive anal sex with multiple partners was not [77].

There are no medications or immunizations to reduce the risk of acquiring HCV after a possible
exposure. Thus, post-exposure management depends upon close monitoring and referral for
treatment if infection does occur. We perform HCV testing in patients who have had a percutaneous
exposure or a high-risk sexual exposure (eg, condomless receptive anal intercourse, sexual assault).

If the patient has no history of HCV infection, we obtain a baseline HCV antibody. We also obtain an
HCV viral load if the patient has signs and symptoms of acute HCV infection (eg, elevated
aminotransaminase levels), or has a partner who is known to have HCV infection.

If the exposed patient tests negative for HCV at baseline, the approach to follow-up depends upon the
HCV status of the source:

● If the source tests negative for HCV RNA, no further testing needs to be performed.

● If the HCV status of the source is positive or unknown, the exposed patient should be tested for
HCV RNA at least three weeks after the exposure. If positive, the patient should be referred to
care; if negative, no further testing is needed.

If the exposed patient was treated for HCV in the past, they are still at risk for reinfection, even if the
HCV antibody is positive. For such patients, we obtain HCV RNA at baseline and at follow-up testing
(if needed), rather than an antibody.

This is one approach to testing and is based upon guidelines from the United States Centers for
Disease Control and Prevention [79]. Additional discussions of HCV testing and diagnosis of HCV are
found elsewhere. (See "Clinical manifestations, diagnosis, and treatment of acute hepatitis C virus
infection in adults", section on 'Patients with discrete HCV exposure' and "Diagnosis and evaluation of
chronic hepatitis C virus infection", section on 'Diagnosis and testing approach'.)

SOCIETY GUIDELINE LINKS

Links to society- and government-sponsored guidelines from selected countries and regions around
the world are provided separately. (See "Society guideline links: HIV prevention" and "Society guideline
links: Diagnosis of hepatitis B" and "Society guideline links: Management of hepatitis B" and "Society
guideline links: Hepatitis B vaccination" and "Society guideline links: Hepatitis C virus infection".)
INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The
Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and
they answer the four or five key questions a patient might have about a given condition. These
articles are best for patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for patients
who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-
mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)

● Basics topic (see "Patient education: Preventing HIV after unprotected sex or needle-sharing
(The Basics)")

● Beyond the Basics topic (see "Patient education: Care after sexual assault (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

● Patients who are potentially exposed to HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV)
through a nonoccupational exposure (eg, sexual or percutaneous) are at risk for acquiring one of
these infections. (See 'Introduction' above.)

● To reduce the risk of HIV transmission, patients who present within 72 hours of a possible
exposure (eg, condomless receptive or insertive vaginal or anal intercourse and/or a
percutaneous exposure to blood, or body fluids contaminated with blood) should be evaluated
for nonoccupational post-exposure prophylaxis (nPEP) with antiretroviral therapy (ART) (see
'General principles of HIV post-exposure management' above and 'Who should receive post-
exposure prophylaxis' above):

• If the source is HIV-infected, we recommend initiating post-exposure prophylaxis (Grade 1C).

• If the source's HIV status is unknown at the time of the exposure, we suggest post-exposure
prophylaxis if the source is at high risk for having HIV (eg, man who has sex with men
[MSM], injection drug user, sex worker), or if the patient has been sexually assaulted (Grade
2C).
 • Some patients may also desire nPEP for HIV if they had condomless sex with a source
whose risk factors are unknown. For such patients, the decision to initiate nPEP depends
upon the route of exposure (table 1), and other cofactors that heighten risk of transmission
(eg, presence of genital ulcer disease). If the indications for nPEP are unclear, clinicians can
also call the National Clinician's Post-Exposure Prophylaxis Hotline at 888-448-4911 for
expert advice.

● Once the need for HIV post-exposure prophylaxis has been determined, the patient should be
given a dose as soon as possible, and within 72 hours of the exposure. Prophylaxis should not be
delayed pending HIV testing of the exposed patient or the source. (See 'Timing of HIV
prophylaxis' above and 'Determining the HIV status of the exposed person' above and
'Determining the HIV status of the source' above.)

● For most patients who initiate nPEP, we suggest a three-drug regimen using tenofovir disoproxil
fumarate-emtricitabine plus an integrase strand transfer inhibitor (eg, raltegravir or dolutegravir)
(table 2) (Grade 2C). (See 'Antiviral therapy' above.)

• For many patients, a dolutegravir-containing regimen is preferred because of the

convenience of once-daily dosing. (See 'Choice of regimen' above.)

• However, for persons of childbearing potential who were not using an effective birth control
method at the time of exposure and in persons early in pregnancy, dolutegravir should be
avoided and raltegravir or a boosted protease inhibitor should be used. Preliminary data
suggest a potential risk of neural tube defects in infants born to women who received
dolutegravir at the time of conception. (See 'Choice of regimen' above and 'Special
considerations' above.)

• If the source is HIV infected and there are concerns for multidrug-resistant virus, we prefer a
regimen that uses dolutegravir or a boosted protease inhibitor (eg, boosted darunavir) as the
third agent. (See 'Special considerations' above.)

● Patients receiving nPEP for HIV should receive a 28-day course of ART. After nPEP is
discontinued, patients should have repeat HIV testing approximately 6 and 12 weeks after the
exposure to assess for seroconversion (table 3). If the source is known and is willing to be
tested, nPEP may be able to be discontinued sooner. (See 'Duration of post-exposure prophylaxis'
above and 'Patient monitoring' above.)

● Patients with a potential nonoccupational exposure to HIV should also be evaluated for HBV and
HCV. If their status is unknown, we test the exposed patient for hepatitis B surface antigen
(HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B surface antibody (anti-HBs), and
 hepatitis C antibody. If the source is willing, they should be evaluated for these infections as well.
Patients with a sexual exposure should also be offered and/or treated for other sexually
transmitted infections, depending upon the type of exposure (table 3). (See 'Testing for hepatitis
B and C virus' above.)

● Patients with a potential sexual or percutaneous exposure to HIV should also be evaluated for
HBV post-exposure prophylaxis. If the source is HBsAg-positive or the HBV status is unknown,
the need for immediate post-exposure prophylaxis depends primarily upon the exposed patient's
HBV immune status and their vaccination history. (See 'Exposure to hepatitis B virus' above.)

● There are no medications or immunizations to reduce the risk of acquiring HCV after a possible
exposure. Thus, post-exposure management depends upon close monitoring and referral for
treatment if infection does occur. We perform HCV testing in patients who have had a
percutaneous exposure or a high-risk sexual exposure (eg, condomless receptive anal
intercourse, sexual assault) unless the source tests negative for HCV RNA. (See 'Exposure to
hepatitis C virus' above.)

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30. Else LJ, Taylor S, Back DJ, Khoo SH. Pharmacokinetics of antiretroviral drugs in anatomical
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32. Yanik EL, Napravnik S, Hurt CB, et al. Prevalence of transmitted antiretroviral drug resistance
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33. Chauveau M, Billaud E, Bonnet B, et al. Tenofovir DF/emtricitabine/rilpivirine as HIV post-

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34. Hamlyn E, McAllister J, Winston A, et al. Is screening for sexually transmitted infections in men
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35. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral
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36. Cohen MS, Chen YQ, McMauley M, et al.. Antiretroviral therapy for the prevention of HIV-1
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37. Rodger AJ, Cambiano V, Bruun T, et al. Sexual Activity Without Condoms and Risk of HIV
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38. Bryant J, Baxter L, Hird S. Non-occupational postexposure prophylaxis for HIV: a systematic
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39. American Red Cross. Eligibility criteria. http://www.redcrossblood.org/donating-blood/eligibility-

requirements/eligibility-criteria-alphabetical-listing (Accessed on April 08, 2016).

40. Katz MH, Gerberding JL. The care of persons with recent sexual exposure to HIV. Ann Intern
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41. Cohen MS. HIV postexposure prophylaxis after sexual assault: why is it so hard to accomplish?
Sex Transm Dis 2008; 35:979.

42. Masciotra S, McDougal JS, Feldman J, et al. Evaluation of an alternative HIV diagnostic
algorithm using specimens from seroconversion panels and persons with established HIV
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43. Nasrullah M, Wesolowski LG, Meyer WA 3rd, et al. Performance of a fourth-generation HIV
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44. http://www.cdc.gov/hiv/pdf/HIVtestingAlgorithmRecommendation-Final.pdf (Accessed on July

24, 2014).

45. Kahn JO, Martin JN, Roland ME, et al. Feasibility of postexposure prophylaxis (PEP) against
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46. Roland ME, Neilands TB, Krone MR, et al. Seroconversion following nonoccupational
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47. Cohen MS, Kashuba AD, Gay C. HIV antiretroviral postexposure prophylaxis: a cautionary note.
Clin Infect Dis 2005; 41:1514.

48. Merchant RC, Mayer KH, Becker BM, et al. Predictors of the initiation of HIV postexposure
prophylaxis in Rhode Island emergency departments. AIDS Patient Care STDS 2008; 22:41.

49. Poynten IM, Jin F, Mao L, et al. Nonoccupational postexposure prophylaxis, subsequent risk
behaviour and HIV incidence in a cohort of Australian homosexual men. AIDS 2009; 23:1119.

50. Lunding S, Katzenstein TL, Kronborg G, et al. The Danish PEP registry: experience with the use
of postexposure prophylaxis (PEP) following sexual exposure to HIV from 1998 to 2006. Sex
Transm Dis 2010; 37:49.

51. Misra K, Udeagu CC. Disparities in Awareness of HIV Postexposure and Preexposure
Prophylaxis Among Notified Partners of HIV-Positive Individuals, New York City 2015-2017. J
Acquir Immune Defic Syndr 2017; 76:132.

52. Donnell D, Mimiaga MJ, Mayer K, et al. Use of non-occupational post-exposure prophylaxis does
not lead to an increase in high risk sex behaviors in men who have sex with men participating in
the EXPLORE trial. AIDS Behav 2010; 14:1182.
53. Mehta SA, Silvera R, Bernstein K, et al. Awareness of post-exposure HIV prophylaxis in high-risk
men who have sex with men in New York City. Sex Transm Infect 2011; 87:344.

54. Zablotska IB, Prestage G, Holt M, et al. Australian gay men who have taken nonoccupational
postexposure prophylaxis for HIV are in need of effective HIV prevention methods. J Acquir
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55. Rocha LM, Campos MJ, Brito J, et al. Acceptability of PrEP among HIV negative Portuguese
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56. Du Mont J, Myhr TL, Husson H, et al. HIV postexposure prophylaxis use among Ontario female
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57. Rodríguez AE, Castel AD, Parish CL, et al. HIV medical providers' perceptions of the use of
antiretroviral therapy as nonoccupational postexposure prophylaxis in 2 major metropolitan
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58. Golub SA, Rosenthal L, Cohen DE, Mayer KH. Determinants of high-risk sexual behavior during
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59. Schechter M, do Lago RF, Mendelsohn AB, et al. Behavioral impact, acceptability, and HIV
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60. Scheer S, Chu PL, Klausner JD, et al. Effect of highly active antiretroviral therapy on diagnoses of
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62. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human
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63. Mofenson LM, Lambert JS, Stiehm ER, et al. Risk factors for perinatal transmission of human
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64. Tokars JI, Marcus R, Culver DH, et al. Surveillance of HIV infection and zidovudine use among
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65. Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health
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66. Roland ME. Postexposure prophylaxis after sexual exposure to HIV. Curr Opin Infect Dis 2007;
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67. Landovitz RJ. Occupational and nonoccupational postexposure prophylaxis for HIV in 2009. Top
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68. Landovitz RJ, Currier JS. Clinical practice. Postexposure prophylaxis for HIV infection. N Engl J
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69. Chin RL. Postexposure prophylaxis for HIV. Emerg Med Clin North Am 2010; 28:421.

70. Smith DK, Grohskopf LA, Black RJ, et al. Antiretroviral postexposure prophylaxis after sexual,
injection-drug use, or other nonoccupational exposure to HIV in the United States:
recommendations from the U.S. Department of Health and Human Services. MMWR Recomm
Rep 2005; 54:1.

71. Otten RA, Smith DK, Adams DR, et al. Efficacy of postexposure prophylaxis after intravaginal
exposure of pig-tailed macaques to a human-derived retrovirus (human immunodeficiency virus
type 2). J Virol 2000; 74:9771.

72. International Healthcare Worker Safety Center, University of Virugina. 2011 EPINet Report: Needl
estick and sharp-object injuries. http://www.healthsystem.virginia.edu/pub/epinet/epinetdatare
ports.html (Accessed March 25, 2014).

73. Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for
hepatitis B virus protection and for administering postexposure management. MMWR Recomm
Rep 2013; 62:1.

74. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted
diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1.

75. New York State Department of Health AIDS Institute. HIV clinical resource. Nonoccupational ex
posures to hepatitis B and C. http://www.hivguidelines.org/clinical-guidelines/post-exposure-pr
ophylaxis/hiv-prophylaxis-following-non-occupational-exposure/ (Accessed on February 03, 201
6).
 76. Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United
States: Recommendations of the Advisory Committee on Immunization Practices. MMWR
Recomm Rep 2018; 67:1.

77. Witt MD, Seaberg EC, Darilay A, et al. Incident hepatitis C virus infection in men who have sex
with men: a prospective cohort analysis, 1984-2011. Clin Infect Dis 2013; 57:77.

78. Tohme RA, Holmberg SD. Is sexual contact a major mode of hepatitis C virus transmission?
Hepatology 2010; 52:1497.

79. Centers for Disease Control and Prevention. Information for healthcare personnel potentially ex
posed to hepatitis C virus (HCV). www.cdc.gov/hepatitis/pdfs/testing-followup-exposed-hc-per
sonnel.pdf (Accessed on August 30, 2017).

Topic 3768 Version 26.0

GRAPHICS

Estimated per-act risk for acquisition of HIV, by exposure route

Risk per 10,000 exposures to an infected

Exposure route
source (risk)

Blood-borne Blood transfusion 9000 (9/10)

exposure
Needle-sharing injection drug use 67 (1/150)

Percutaneous needle stick 23 (1/435)

Mucous membrane exposure to blood (eg, splash to eye) 10 (1/1,000)

Sexual exposure Receptive anal intercourse 138 (1/72)

Insertive anal intercourse 11 (1/900)

Receptive penile-vaginal intercourse 8 (1/1250)

Insertive penile-vaginal intercourse 4 (1/2500)

Receptive or insertive penile-oral intercourse 0-4

Other Biting, spitting, throwing body fluids (including semen Negligible 

and saliva), sharing sex toys

There are scant empiric data on per contact risk of exposure. This table lists the estimated risk by exposure type in the absence of
antiretroviral treatment of the HIV-infected source and in the absence of amplifying factors. Most of these estimates are derived
through modeling studies of different cohorts. Clinicians need to be aware that estimates of sexual risk are often based on studies of
monogamous couples among whom amplifying factors have been treated and repeated exposure may offer as yet unexplained
protection from infection. Using a single value for assessing risk of HIV transmission based on route of sexual exposure fails to reflect
the variation associated with important cofactors. A variety of amplifying factors and conditions have been identified, and these factors
can be expected to increase transmission probability.

Data from:
1. Donegan E, Stuart M, Niland JC, et al. Infection with human immunodeficiency virus type 1 (HIV-1) among recipients of antibody-positive
blood donations. Ann Intern Med 1990; 113:733-9.
2. Baggaley RF, Boily MC, White RG, Alary M. Risk of HIV-1 transmission for parenteral exposure and blood transfusion: A systematic review and
meta-analysis. AIDS 2006; 20:805.
3. Kaplan EH, Heimer R. HIV incidence among New Haven needle exchange participants: updated estimates from syringe tracking and testing
data. J Acquir Immune Defic Syndr 1995; 10:175-6.
4. Patel P, Borkowf CB, Brooks JT, et al. Estimating per-act HIV transmission risk: A systematic review. AIDS 2014; 28:1509-19.
5. Cohen MS. Amplified transmission of HIV-1: Missing link in the HIV pandemic. Trans Am Clin Climatol Assoc 2006; 117: 213–225.
6. Centers for Disease Control and Prevention, US Department of Health and Human Services. Updated Guidelines for Antiretroviral
Postexposure Prophylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV—United States, 2016.

Graphic 60145 Version 5.0

Management of possible exposure to HIV
The HIV status of the source should be classified as HIV-positive or unknown at the time of the initial evaluation. Thus, treatment decisions s
exposure and when the exposure occurred. Once the need for nPEP has been identified, the patient should receive a dose as soon as possible
testing of the exposed patient and source have not yet been performed. After the initial dose has been administered, HIV testing and a more d
patients should also be assessed for hepatitis B and C virus, and sexually transmitted infections (depending upon the type of exposure).

ART: antiretroviral therapy; EVG/c/FTC/TDF: Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate; FTC: emtricitabine; nPEP: nonoccupatio
disoproxil fumarate. Antiretroviral abbreviations separated by "/" (eg, TAF/FTC) are available in single-tablet coformulations.
* High-risk exposure includes: Having condomless receptive or insertive vaginal or anal intercourse with a source who is HIV-infected, or a source whos
(eg, men who have sex with men, injection drug users, sex workers); having a percutaneous exposure to blood (or body fluids contaminated with blood
factors described above; or having been sexually assaulted.
¶ Preferred regimens: The coformulated tablet TDF/FTC in combination with raltegravir or dolutegravir. Alternative regimens include: EVG/c/FTC/TDF, T
darunavir plus ritonavir or darunavir/cobicistat), or rilpivirine/emtricitabine/TDF. There is an increased risk of drug interactions if a pharmacologic boos
Δ For individuals with reduced kidney function, TDF and FTC cannot be administered as a coformulated tablet and the dosage must be adjusted accord
and cobicistat should only be administered together if the eGFR is >70 mL/min/1.73 m 2.
◊ If the source patient is at risk for having drug-resistant virus (eg, those who have failed multiple regimens as well as those with known non-adherence
tablet TDF/FTC in combination with dolutegravir. An alternative regimen is TDF/FTC plus a pharmacologically-boosted PI (eg, darunavir plus ritonavir o
managed in conjunction with an experienced HIV provider.
§ Refer to the topic that discusses the clinical manifestations of acute HIV infection.
¥ HIV-infected patients with a stably suppressed viral load are unlikely to transmit HIV. Decisions to continue nPEP should be made on a case-by-case b

Graphic 108662 Version 1.0

Antiretroviral regimens for post-exposure prophylaxis following an exposure to HIV

Preferred regimen
Tenofovir disoproxil fumarate-emtricitabine* plus one of the following:

Raltegravir 400 mg twice daily

Dolutegravir 50 mg once daily ¶

Alternative regimens
Elvitegravir-cobicistat-emtricitabine-tenofovir disoproxil fumarate Δ◊

Tenofovir disoproxil fumarate-emtricitabine* plus a pharmacologically boosted protease inhibitor Δ◊§

Rilpivirine-emtricitabine-tenofovir disoproxil fumarate*

Antiretroviral agents separated by "-" are available in single-tablet coformulations

* The approach to regimen selection in patients with reduced kidney function can vary and is discussed in the topic reviews on occupational and
nonoccupational exposures to HIV. If tenofovir disoproxil fumarate and emtricitabine are used in individuals with an estimated glomerular
filtration rate <50 mL/min, the dosage of tenofovir disoproxil fumarate and emtricitabine should be adjusted based upon kidney function, and
coformulated tablets cannot be used. For specific dosing recommendations, refer to the individual Lexicomp drug monographs available in
UpToDate.
¶ Dolutegravir should not be prescribed to any person of childbearing potential who is sexually active or has been sexually assaulted and was not
using an effective birth control method. It should also be avoided in persons early in pregnancy (eg, eight weeks since last menstrual period).
Preliminary reports suggest an increased rate of neural tube defects in infants born to women who received dolutegravir at the time of
conception. Additional information on regimen selection in this population can be found in the topics that discuss management after a potential
exposure to HIV.
Δ There is an increased risk of drug interactions if a regimen using a boosting agent (ie, cobicistat or ritonavir) is administered. In addition,
regimens that contain tenofovir disoproxil fumarate and cobicistat should only be administered to individuals with an estimated glomerular
filtration rate ≥70 mL/min.
◊ Elvitegravir-cobicistat-emtricitabine-tenofovir disoproxil fumarate and other cobicistat-containing regimens should not be used in persons of
childbearing potential who desire pregnancy or in those who are pregnant due to decreased drug levels during pregnancy.
§ In general, we prefer darunavir boosted with ritonavir or the coformulated tablet darunavir-cobicistat if a protease inhibitor is used. However,
darunavir should generally be avoided in patients with a sulfonamide allergy. Atazanavir boosted with ritonavir or the coformulated tablet
atazanavir-cobicistat can be used as an alternative.

Graphic 83598 Version 10.0

Recommended laboratory evaluation for nonoccupational post-exposure prophylaxis (nPEP) of HIV
infection*

4 to 6 weeks after 3 months after 6 months after

Test Baseline
exposure exposure exposure

HIV serologic testing ¶ E, S Δ E E E◊

Complete blood count with differential § E      

Serum liver enzymes (ALT, AST) E E    

Blood urea nitrogen/creatinine E E    

Sexually transmitted diseases screen E, S E‡   E‡

(gonorrhea, chlamydia, syphilis) ¥

Hepatitis B serology (HBsAg, anti-HBs, anti- E, S     E†

HBc)

Hepatitis C serology E, S **     E

Pregnancy test (for women of reproductive age) E E (if sexual exposure)    

HIV viral load ¶ ¶ S (only if HIV-      

infected)

HIV resistance testing ¶ ¶ S (only if HIV-      

infected)

ALT: alanine aminotransferase; AST: aspartate aminotransferase; HBV: hepatitis B virus; HCV: hepatitis C virus; E: exposed patient; S: source;
HBsAg: hepatitis B surface antigen.
* This table is designed to monitor asymptomatic patients receiving tenofovir disoproxil fumarate-emtricitabine as the nucleoside combination
with a third agent (eg, an integrase inhibitor or a boosted protease inhibitor). Additional testing (eg, for pregnancy, sexually transmitted diseases,
hepatitis) should be performed if clinically indicated.
¶ A lab-based fourth-generation HIV antigen-antibody assay is the preferred test.
Δ HIV serologic testing is indicated for sources of unknown serostatus.
◊ Only if patient became acutely infected with HCV.
§ If zidovudine-lamivudine is used as the nucleoside combination, a complete blood count should be performed while the patient is receiving
nonoccupational post-exposure prophylaxis (after approximately two weeks). 
¥ For patients with a sexual exposure. Refer to the topic review in UpToDate that discusses screening of sexually transmitted infections.
‡ Syphilis testing should be performed four to six weeks and six months after a sexual exposure. Chlamydia and gonorrhea testing should be
performed four to six weeks after a sexual exposure for those who were not treated empirically at baseline and for those who are symptomatic.  
† For patients who were not immune at baseline and were exposed to a source who is HBsAg-positive or whose HBsAg status is unknown. Refer
to the UpToDate topic that discusses nonoccupational exposures to HBV for a discussion of HBV post-exposure prophylaxis.
** If the source tests positive for HCV, additional monitoring of the exposed patient may be required. Refer to the UpToDate topic review that
discusses the diagnosis of acute HCV in adults.
¶¶ For the exposed patient, virologic testing should only be performed if symptoms of acute HIV infection develop or if the patient is found to be
HIV-infected on serologic testing.

Adapted from: United States Centers for Disease Control and Prevention. Updated guidelines for antiretroviral postexposure prophylaxis after sexual,
injection drug use, or other nonoccupational exposure to HIV—United States, 2016. http://stacks.cdc.gov/view/cdc/38856 (Accessed on April 20,
2016).

Graphic 66128 Version 5.0

Management of possible nonoccupational exposure to hepatitis B virus
This algorithm reflects our approach to HBV post-exposure prophylaxis after a nonoccupational exposure, and is a synthesis of guideline reco

HBV: hepatitis B virus; anti-HBc: antibodies to hepatitis B core antigen; anti-HBs: antibodies to hepatitis B surface antigen; HBIG: hepatitis B immune gl
* Clinicians should evaluate patients for post-exposure prophylaxis if the patient had a percutaneous (eg, bite or needlestick) or mucosal exposure to b
contain blood).
¶ Routine hepatitis B vaccination should still be administered to all exposed individuals who engage in high-risk behaviors if they are not immune or are
discusses hepatitis B vaccination.
Δ If the exposed patient is uncertain if they completed the hepatitis B vaccine, they should be treated as if they are unvaccinated.
◊ If the HBV status of the source is unknown at the time of exposure and the source is willing to be tested, HBsAg, anti-HBs, anti-HBc should also be ob
management after a nonoccupational exposure should not be delayed pending the results of serologic testing (of the exposed patient or the source).
§ HBIG and/or hepatitis B vaccine should be administered within 24 hours. If the hepatitis B vaccine and HBIG are given simultaneously, they should be
particular HBIG) are not always available in the emergency room or primary care setting. If HBIG is delayed, hepatitis B vaccine should be given as soon
¥ HBIG can still be effective if administered within 7 days of a percutaneous exposure or 14 days of a sexual exposure.
‡ Individuals who have received two courses of the hepatitis B vaccine series are unlikely to respond to additional doses.
† HBIG can be discontinued if serologic testing reveals the source is HBsAg-negative.

References:
1. Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering post
2. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm R
3. New York State Department of Health AIDS Institute. HIV clinical resource. Nonoccupational exposures to hepatitis B and C. http://www.hivguidelin
prophylaxis-following-non-occupational-exposure/ (Accessed on February 03, 2016).

Graphic 108661 Version 2.0

Post-exposure prophylaxis to hepatitis B virus after a nonoccupational exposure

Treatment when source patient is:

Vaccination and/or antibody
response status of exposed person* HBsAg-positive/source unknown or not
HBsAg-negative ¶
available for testing

Unvaccinated/nonimmune HBIG Δ × 1; initiate HBV vaccine series Initiate HBV vaccine series

Previously vaccinated ◊, known responder § No treatment No treatment

Previously vaccinated ◊, known HBIG Δ × 1 and initiate revaccination ¥ or No treatment

nonresponder § HBIG Δ × 2

Previously vaccinated ◊, antibody response Single vaccine booster dose No treatment

unknown ‡

If still undergoing vaccination HBIG Δ × 1; complete series Complete series

anti-HBc: antibody to hepatitis B core antigen; anti-HBs: antibody to hepatitis B surface antigen; HBsAg: hepatitis B surface antigen; HBIG:
hepatitis B immune globulin; HBV: hepatitis B virus.
* Persons who have previously been infected with HBV are immune to reinfection and do not require post-exposure prophylaxis.
¶ A source is considered HBsAg-negative if at the time of exposure they are known to have either of the following: anti-HBs ≥10 milli-international
units/mL after immunization or resolved HBV (anti-HBs-positive and anti-HBc-positive).
Δ For specific recommendations on dosing and administration of HBIG, refer to the topic that discusses post-exposure prophylaxis after a
nonoccupational exposure to HBV and the drug information topic within UpToDate.
◊ Vaccinated with full three-dose series.
§ Based on information available at presentation. Responder is defined as person with previously documented adequate levels of serum
antibody to HBsAg (serum anti-HBs ≥10 milli-international units/mL); nonresponder is a person with previously documented inadequate
response to vaccination (serum anti HBs<10 milli-international units/mL). It is recommended that decision-making not be delayed while testing
for anti-HBs at presentation.
¥ The option of giving one dose of HBIG and reinitiating the vaccine series is preferred for nonresponders who have not completed a second
three-dose vaccine series. For persons who previously completed a second vaccine series but failed to respond, two doses of HBIG are
preferred.
‡ The need for additional prophylaxis (eg, hepatitis B vaccine and HBIG) depends upon serologic testing performed at the time of the initial
evaluation. Refer to the UpToDate topic that discusses post-exposure prophylaxis for HBV.

References: 
1. HIV Clinical Resource. UPDATE: HIV prophylaxis following non-occupational exposure. Available at: http://www.hivguidelines.org/clinical-
guidelines/post-exposure-prophylaxis/hiv-prophylaxis-following-non-occupational-exposure/ (Accessed on February 2, 2016). Copyright ©
2014 New York State Department of Health AIDS Institute's Clinical Guidelines Development Program.
2. CDC Guidance for Evaluating Health-Care Personnel for Hepatitis B Virus Protection and for Administering Postexposure Management.
MMWR Recomm Rep 2013; 62:1.
3. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR
Recomm Rep 2015; 64:1.

Graphic 106531 Version 2.0

Recommended doses of formulations of recombinant hepatitis B vaccines licensed in the United States
for persons age 18 and older, by age group and vaccine type*

Dose
Age group and associated Volume
  HBsAg Recommended schedule ¶
conditions (mL)
(mcg)

Single-antigen vaccines

Recombivax HB

Pediatric/adolescent 18 through 19 years 0.5 5 0, 1, and 6 months Δ

formulation

Adult formulation ≥20 years 1 10

Dialysis formulation ≥20 years and receiving 1 40 0, 1, and 6 months

dialysis ◊

Engerix-B 18 through 19 years 0.5 10 0, 1, and 6 months Δ

≥20 years 1 20

≥20 years and receiving 2§ 40 0, 1, 2, and 6 months

hemodialysis ◊

Heplisav-B ¥ ≥18 years 0.5 20 0 and 1 months

Combination vaccine

Twinrix (combined HepB- ≥18 years 1 20 Standard: 0, 1, and 6 months

HepA vaccine) Accelerated: 0, 7, and 21 to 30
days, and 12 months

HBsAg: hepatitis B surface antigen; HepA: hepatitis A; HepB: hepatitis B.

* For recommended doses for persons <18 years of age, refer to UpToDate content on HepB vaccines for children.
¶ The hepatitis B vaccine series does not need to be restarted if the second or third dose is delayed.
Δ An alternative accelerated schedule is 0, 1, 2, and 12 months. Accelerated schedules provide a more rapid antibody response (may be of use
for travelers).
◊ The increased dose of HBsAg (40 mcg) may also be reasonable for immunocompromised hosts. Refer to the topics that discuss hepatitis B
immunization in adults and immunization in patients with end-stage renal disease for additional information.
§ This is a double dose of the standard formulation of Engerix-B for patients ≥20 years of age (Engerix-B does not have a separate dialysis
formulation).
¥ Heplisav-B contains 3000 mcg of immunostimulatory phosphorothioate oligodeoxyribonucleotide as an adjuvant.

Data from:
1. Schillie S, Vellozzi C, Reingold A, et al. Prevention of hepatitis B virus infection in the United States: Recommendations of the Advisory
Committee on Immunization Practices. MMWR Recomm Rep 2018; 67:1.
2. Schillie S, Harris A, Link-Gelles R, et al. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B
Vaccine with a Novel Adjuvant. MMWR Morb Mortal Wkly Rep 2018; 67:455.
3. HEPLISAV-B (hepatitis B vaccine [recombinant], adjuvanted). United States Prescribing Information. November 2017, US Food and Drug
Administration. Available at: https://www.fda.gov/BiologicsBloodVaccines/default.htm (Accessed on April 12, 2018).

Graphic 117603 Version 2.0

Contributor Disclosures
Judith A Aberg, MD Grant/Research/Clinical Trial Support: GSK [HIV investigational study on attachment
inhibitor (fostemsavir)]; Gilead [HIV (Tenofovir alenfenamide)]; Viiv [Long acting injectables (Cabotegravir,
rilpivirine)]; Frontier Technology (Albuvirtide, 3BNC117). Consultant/Advisory Boards: Gilead [HIV (TDF)]; Janssen
[HIV (Darunavir)]; Merck [HIV (Raltegravir, Doravirine)]; Viiv [HIV [ABC, 3TC, DTG)]. Demetre C Daskalakis, MD,
MPH Nothing to disclose John G Bartlett, MD Nothing to disclose Paul E Sax, MD Grant/Research/Clinical Trial
Support: Gilead Sciences [HIV (tenofovir, emtricitabine, elvitegravir, cobicistat)]; GlaxoSmithKline [HIV
(lamivudine, abacavir, dolutegravir)]. Consultant/Advisory Boards: Gilead Sciences [HIV (tenofovir, emtricitabine,
elvitegravir, cobicistat)]; GlaxoSmithKline [HIV (lamivudine, abacavir, dolutegravir)]; Janssen Pharmaceuticals
[HIV (darunavir, etravirine, rilpivirine)]; Merck [HIV (raltegravir)]. Meg Sullivan, MD Grant/Research/Clinical Trial
Support: Gilead Sciences [Pre-exposure prophylaxis for contraception (Tenofovir)]. Consultant/Advisory Boards:
Gilead Sciences [Pre-exposure prophylaxis for contraception (Tenofovir)].

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.

Conflict of interest policy