Nonoccupational Postexposure Prophylaxis


Although avoiding exposure to HIV is the only reliable way of preventing HIV infection, postexposure prophylaxis (PEP) can decrease the risk of infection after exposure to HIV. Antiretroviral (ARV) therapy is an important prophylactic intervention for appropriate persons with nonoccupational exposures (e.g., sexual contact; sharing of injection drug needles or other equipment) as well as those with occupational exposures (e.g., needlesticks). The U.S. Department of Health and Human Services (HHS) has developed recommendations for nonoccupational PEP (nPEP) based on data from animal models, perinatal clinical trials, and observational studies. Efficacy of nPEP remains hypothetical, and randomized clinical trials are not possible, but nPEP appears to be safe.

Figure 1. Exposure Risk Algorithm

Exposure Risk Algorithm

U.S. Department of Health and Human Services. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States. MMWR Recomm Rep. 2005 Jan 21;54(RR02);1-20.

Figure 1. Exposure Risk Algorithm

Exposure Risk Algorithm

U.S. Department of Health and Human Services. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States. MMWR Recomm Rep. 2005 Jan 21;54(RR02);1-20.

Overall, nPEP is more likely to be effective when the exposure is a single episode and nPEP is initiated in a timely manner. It is not appropriate for cases of multiple sexual exposures or injection drug use (IDU) exposures over time or for exposures that occurred >72 hours before starting nPEP treatment (see Figure 1).

The model for nPEP is derived in part from protocols for occupational PEP (e.g., in terms of risk assessment, pretreatment testing, timing of treatment, treatment regimens, and duration of treatment). (For information on occupational PEP, see chapter Occupational Postexposure Prophylaxis .) One significant difference between the protocols is that nPEP protocols should include interventions to reduce the risk of future HIV acquisition. Although exposed individuals usually seek care because they are interested specifically in antiretroviral prophylaxis, the nPEP model takes advantage of a critical opportunity to provide risk-reduction counseling and education.

see chapter Occupational Postexposure Prophylaxis for further discussion of evaluating possible benefits and risks of PEP.

S: Subjective

The patient reports potential exposure to HIV through a sexual encounter or the sharing of needles or other equipment for IDU.

Take a thorough history of the specific sexual or drug-use activities, the time the exposure occurred, the HIV status of the source person (if known), and HIV risk factors of the source person (if HIV status is not known). In cases of sexual assault, evidence collection and specific paperwork may be required as well.

O: Objective

Examine for trauma and for signs or symptoms of sexually transmitted diseases (STDs), which may increase the risk of HIV transmission. In injection drug users, examine for abscesses and signs or symptoms of infection. For women who may be pregnant, perform a pregnancy test.

A: Assessment

Assess for potential exposures to HIV and other bloodborne pathogens and for the presence of other STDs. The risk of HIV infection depends on the HIV status of the source and on the characteristics of the source (e.g., HIV viral load) and of the exposure (see Figure 1). Note that, although an undetectable HIV viral load is thought to indicate a low risk of HIV transmission, transmission still is possible, and cases of sexual transmission from sources with undetectable serum HIV RNA have been reported.

The estimated risk of HIV exposure will determine whether nPEP should be offered. An algorithm for risk evaluation and treatment decisions is presented in Figure 1.

P: Plan

Laboratory Testing

  • Perform a baseline HIV antibody test.
  • Evaluate and test for other infections transmitted through sexual or IDU exposures, including chlamydia, gonorrhea, syphilis, herpes simplex virus, hepatitis B (HBV surface antigen, surface antibody, and core antibody), and hepatitis C (HCV antibody).
  • Obtain complete blood count (CBC), liver function tests (LFTs), and creatinine and estimated glomerular filtration rate (GFR) at baseline before treatment with ARV medications.


Follow the algorithm in Figure 1 to determine whether the patient should be offered nPEP medications. If the patient is a candidate for treatment, provide counseling about the potential risks and benefits of nPEP.

Select an nPEP regimen that is likely to be effective but tolerable; consider the potential adverse effects and drug interactions of ARV agents (Table 1). Adherence to nPEP is strongly affected by factors such as the tolerability of the ARVs, the number of pills in the regimen, and the frequency of dosing. It is very important to select a regimen that is expected to be tolerated and that is convenient to take; any side effects or adherence difficulties should be managed promptly.

In general, the recommendations for nPEP involve 3-drug combination therapy. In some circumstances, more than 3 ARVs may be appropriate (e.g., if the source virus is resistant to ARVs), and in some cases, 2-drug PEP may be considered (e.g., if the HIV status of the source person is unknown, the exposure is thought to be of relatively low risk, or there is a need to minimize possible toxicity); consultation with experts is recommended.

Note that the HHS nPEP guidelines were last updated in 2005 and do not reflect current practice. The recommendations presented here have been adapted to reflect current nPEP strategies, current guidelines for occupational PEP, and the availability of newer ARVs (see Table 1). Note that a number of ARVs that were included in "preferred" or "alternative" regimens in the 2005 guidelines are no longer recommended in current practice, based on factors such as higher likelihood of causing adverse effects, greater pill burden, or inconvenient dosing. A number of alternatives to the recommendations listed below are available; consult with an expert. Note that, although these regimens are effective in treating HIV infection, their efficacy as prophylaxis has not been demonstrated.

If the source person is known or suspected to have infection with HIV that is resistant to ARV medications, seek expert consultation in selecting an appropriate nPEP regimen.

Certain ARVs are not currently recommended for PEP, including nevirapine (which is contraindicated for PEP), abacavir (testing for HLA-B*5701 must be done), didanosine, enfuvirtide, and tipranavir. Although the 2005 nPEP guidelines designate it as a preferred agent, efavirenz may have a higher rate of significant adverse effects than other agents listed in Table 1. Additionally, efavirenz should not be used during the first trimester of pregnancy or for women who may become pregnant while taking PEP, because of possible teratogenicity. Refer to the updated occupational PEP guidelines and to the adult and adolescent ARV treatment guidelines for more complete information on the advantages and disadvantages, adverse effects, and drug-drug interactions of the various ARV agents available for PEP (references below). Consider consultation with experts (see "Expert Consultation," below).

Table 1. Antiretroviral Regimens for Nonoccupational Postexposure Prophylaxis of HIV Infection*
* Forthcoming HHS guidelines on nPEP may differ from these recommendations; check current recommendations.

Abbreviations: NNRTI = nonnucleoside reverse transcriptase inhibitor; NRTI = nucleoside analogue reverse transcriptase inhibitor; PI = protease inhibitor

Adapted from Kuhar DT, Henderson DK, Struble KA, et al.; U.S. Public Health Service Working Group. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to Human Immunodeficiency Virus and Recommendations for Postexposure Prophylaxis. Infect Control Hosp Epidemiol. 2013 Sep;34(9):875-92; and U.S. Department of Health and Human Services. Antiretroviral Postexposure Prophylaxis After Sexual, Injection-Drug Use, or Other Nonoccupational Exposure to HIV in the United States-January 21, 2005 . Accessed December 1, 2013.

Preferred Regimens
  • Raltegravir 400 mg BID + tenofovir 300 mg/emtricitabine 200 mg QD (Truvada)
Alternative Regimens

(combine 1 drug or drug pair from left column with 1 NRTI pair from right column)

  • Raltegravir 400 mg BID
  • Darunavir 800 mg QD + ritonavir 100 mg QD
  • Etravirine 200 mg BID
  • Rilpivirine 25 mg QD
  • Atazanavir 300 mg QD + ritonavir 100 mg QD
  • Lopinavir/ritonavir 400/100 mg BID


  • Tenofovir + emtricitabine (Truvada), 1 tablet QD
  • Tenofovir 300 mg QD + lamivudine 300 mg QD
  • Zidovudine + lamivudine (Combivir), 1 tablet BID
  • Zidovudine 300 mg BID + emtricitabine 200 mg QD


  • Elvitegravir/cobicistat/tenofovir/emtricitabine (Stribild) (complete regimen; no additional NRTIs needed)

Once the decision is made to institute nPEP, do the following:

  • Begin ARV prophylaxis as soon as possible after the exposure, but always within 72 hours. Treatment should be continued for 28 days, unless the source person is determined to be HIV negative.
  • Provide counseling about the efficacy of nPEP, timely initiation of nPEP medications, adherence to the regimen for 28 days, and the importance of preventing additional HIV exposures during this time.
  • Counsel exposed patients to use latex barriers with their sex partners until transmission of HIV infection has been ruled out.
  • Counsel patients, as appropriate, about ways to reduce risks of future exposure to HIV.
  • In cases of sexual assault, refer the patient to a rape counselor.


Patients should be evaluated within 1 week for review of all test results and further risk-reduction counseling. For patients taking nPEP, this follow-up should include adherence assessment and evaluation of any adverse effects. Side effects should be managed aggressively in order to maximize the likelihood of adherence to nPEP. A 2-week blood screening (CBC, LFTs, and creatinine) should be performed for patients on the 28-day nPEP regimen to monitor for nPEP toxicity.

Follow-up testing for HIV antibody in patients with a negative baseline HIV antibody test should be done at 6 weeks, 3 months, and 6 months after the exposure. If a 4th-generation HIV Ag/Ab assay is used, the final HIV test can be done at 4 months rather than 6 months.

Patients need health education and risk-reduction counseling and emotional support during their follow-up visits. Nonoccupational PEP programs should focus efforts on risk-reduction counseling rather than the continued use of medicines for prevention. To this end, many programs have case managers, social workers, and health educators as the key providers of follow-up and counseling after an exposure, with referral to clinicians as needed.

If patients develop acute HIV infection or are discovered to be HIV seropositive at follow-up testing, immediately refer to an HIV specialist for evaluation and care (see chapter Early HIV Infection ).

Expert Consultation

For consultation on the treatment of exposures to HIV (and HBV and HCV), the clinician managing the exposed person can call the National HIV/AIDS Clinicians' Post-Exposure Prophylaxis Hotline (PEPline) at 888-HIV-4911 (888-448-4911). This service is available 7 days a week at no charge. Additional information on the Internet is available at PEPline support may be especially useful in challenging situations, such as when drug-resistant HIV strains are suspected to be involved in the exposure or when the exposed person is pregnant.

Prophylaxis Against HBV and HCV

Prophylaxis against HBV is recommended for patients with potential exposure to HBV who do not have not have immunity against HBV. Give HBV immune globulin (HBIG) as a 0.06 mL/kg IM injection and initiate the vaccination series. For patients who previously received the vaccine series but did not develop protective antibody (HBV sAb+), give HBIG at the time of the postexposure workup and initiate revaccination; consider repeat of HBIG in 1 month. For patients with immunity to HBV (HBV sAb+), no treatment is indicated.

For HCV, no prophylactic treatments are recommended. After potential exposure, perform a baseline HCV antibody test. If the source is known to have HCV infection, consider alanine aminotransferase (ALT) and HCV viral load testing at 4-6 weeks. HCV antibody testing should be repeated at 4-6 months. If HCV seroconversion occurs (indicated by ALT elevation, detectable HCV viral load, or confirmed positive HCV antibody test result), refer the patient to a hepatitis C specialist because early treatment of acute HCV may be indicated.

Patient Education

  • Persons who have possible exposures to HIV should contact a medical provider or go to an emergency room as soon as possible after the potential exposure has occurred. PEP may be effective if it is started within 72 hours of exposure, but the sooner medications are initiated, the better the chance for preventing HIV transmission.
  • PEP medications should be taken as directed for a full 28-day course. Adherence to PEP medications is essential for successful treatment.
  • If patients are experiencing uncomfortable adverse effects, they should contact their care provider right away. Providers may prescribe medications to alleviate the adverse effects or select other PEP medications.
  • Until HIV infection has been ruled out, exposed persons should be advised to use latex barriers to prevent transmission of HIV to their sex partners.
  • Exposed persons should be counseled about the symptoms of primary HIV infection and instructed to contact their care provider immediately if symptoms develop.
  • The most effective way to prevent HIV infection is to prevent exposure to HIV by practicing safer sex and safer IDU techniques. Use of condoms and other latex or polyurethane barriers and avoidance of needle sharing are successful preventive measures. If patients have questions about access to condoms or clean needles, they should contact their care provider for assistance.