Management of nonoccupational exposures to HIV and hepatitis B and C in adults

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 "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 selection and management in pregnant individuals with HIV in resource-rich settings".)

●(See "Prevention of vertical 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 has HIV. We also suggest nPEP when the HIV status of the source is unknown if the source is at high risk for having HIV (eg, man who has sex with men, person who uses injection drugs, 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 in the emergency department", section on 'Management'.)

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 "HIV pre-exposure prophylaxis", section on 'Persons receiving 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. For most patients, we suggest:

●Tenofovir disoproxil fumarate-emtricitabine (TDF/FTC)

PLUS

●An integrase strand transfer inhibitor (eg, raltegravir [400 mg twice daily] or dolutegravir [50 mg once daily])

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.)

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.

More detailed information on the choice of regimen in certain patient groups (eg, persons who are of childbearing potential or are pregnant, persons with reduced kidney function, persons exposed to a source with known HIV) can be found below. (See 'Special considerations' below.)

There are insufficient data to support the routine use of tenofovir alafenamide (TAF) in place of tenofovir disoproxil fumarate (TDF) for nPEP. TAF 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 patients with HIV [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 found tenofovir alafenamide-emtricitabine (TAF/FTC) to be noninferior to TDF/FTC for PrEP [19]. (See "HIV pre-exposure prophylaxis".)

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 have HIV infection 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 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 creatinine clearance <50 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/FTC 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 – Persons who are pregnant or of childbearing potential can use tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) plus either raltegravir or dolutegravir. (See 'Choice of regimen' above.)

Previously, dolutegravir was avoided in persons who were early in their pregnancy or were able to become pregnant but were not using effective birth control [20]. This was based on a preliminary report suggesting an increased rate of neural tube defects in infants born to women in Botswana who were receiving dolutegravir at the time of conception (the risk of a fetus developing a neural tube defect during the first 28 days) [21,22]. However, after accrual of further data, the risk with dolutegravir exposure was not found to be statistically different compared with exposure to non-dolutegravir-containing antiretroviral therapy around the time of conception [23].

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. In addition, bictegravir should be avoided since there is limited experience with the use of this agent during pregnancy.

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 [24-26], and completion rates [27-29]. As examples:

●Using tenofovir-emtricitabine as the NRTI combination – There has been extensive use of coformulated TDF/FTC 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 [25]. The main concerns with the use of TDF/FTC 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 [27-29]. 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 TDF/FTC was well tolerated as nPEP, except for a few cases where patients developed myalgias and elevation of creatinine kinase levels [30,31]. Raltegravir also achieves higher concentrations in the male and female genital tract than PIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs) [32,33]. 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 TAF, which we do not routinely 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 a cobicistat-boosted regimen (eg, elvitegravir-cobicistat-emtricitabine-tenofovir disoproxil fumarate) because of concerns about adequate levels during pregnancy or bictegravir since there is limited experience with this regimen. (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 [34]. Although we don't routinely use rilpivirine, it has been studied for post-exposure prophylaxis and is a recommended option in some countries [35].

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 treatment-naïve persons with HIV-1: General approach".)

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 have HIV, 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 2).

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 in the emergency department".)

●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 [36]. 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 has HIV and a suppressed HIV RNA on ART, since such patients are at very low risk of transmitting HIV [37-39]. 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 [27-30,40]. 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 [30]. 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 treatment-naïve persons with HIV-1: General approach".)

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 persons with HIV are expected to seroconvert.

•Refrain from donating blood, plasma, organs, tissue, or semen. The usual duration for this precaution is 12 months [41].

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) [11,42]. These strategies are reviewed elsewhere. (See "HIV infection: Risk factors and prevention strategies", section on 'Clinical approach to HIV prevention' and "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 2). 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 [43]. 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 2). 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 [44-46].

•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 2). 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. 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 [47].

Failure of prophylaxis — Patients should be informed that there are instances of nPEP failure [48]. Reasons for failure may include poor adherence to the nPEP regimen, suboptimal treatment regimens, delays in initiation, or ongoing HIV exposures [49]. 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 patients with HIV who are failing therapy".)

Additional considerations

●Barriers to post-exposure prophylaxis – Many individuals are not aware of nPEP [47,50-53]. 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 [54]. 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 [55]. 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 [51,52,56,57]. In a survey of MSM in Australia, awareness of nPEP increased from 23 percent in 2001 to 64 percent in 2010 [56]. 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 [50]. 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 [58]. 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 [59].

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 [60]. 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 [27]:

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

•Heterosexuals after unprotected receptive anal intercourse.

•Intravenous drug users sharing needles with a person with HIV.

●Increased behavioral risk – Conflicting data have been published as to whether nPEP may lead to an increase in high-risk sexual behaviors [24,50,61,62]. 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 [63].

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 [64-67]. 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 [8,9,15,40,68-71].

Placebo-controlled clinical trials of post-exposure prophylaxis for nonoccupational HIV exposures have not been performed [72]. Thus, the data supporting the efficacy of ART for nPEP is limited to animal studies and observational data [27-30,47,61,73]. 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 [61]. 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 [47]. 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) [27]. 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 [74]. 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 3), 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 in adults".)

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 3 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 in adults", 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 3), 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 [75-77].

Our approach is consistent with the United States Centers for Disease Control and Prevention guidelines for occupational HBV post-exposure prophylaxis [75,78]. 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 [78], or if the source is at high risk for being HBsAg-positive (eg, injection drug users, sexually active men who have sex with men) [77]. (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 3).

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 4). 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 3). 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 3).

●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 4). 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 in adults", 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 [79,80]. 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 participants with and without HIV, whereas unprotected insertive anal sex with multiple partners was not [79].

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 [81]. 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 "Screening and diagnosis of chronic hepatitis C virus infection", section on 'Diagnosis'.)

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 5^th to 6^th 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 10^th to 12^th 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 has HIV, 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 (TDF/FTC) plus an integrase strand transfer inhibitor (eg, raltegravir or dolutegravir) (Grade 2C). (See 'Antiviral therapy' above.)

If the source has HIV 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. There are also certain considerations for regimen selection in other patient groups (eg, persons who are of childbearing potential or are pregnant, persons with reduced kidney function). (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 2). 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 2). (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.)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Demetre Daskalakis, MD, MPH, who contributed to an earlier version of this topic review.

UpToDate also gratefully acknowledges John G Bartlett, MD (deceased), who contributed as Section Editor on earlier versions of this topic and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.