What is the recommended post-exposure prophylaxis (PEP) regimen for a gay male who has been exposed to Human Immunodeficiency Virus (HIV)?

Post-Exposure Prophylaxis for Gay Males After HIV Exposure

For gay males with potential HIV exposure, initiate a 28-day course of three-drug highly active antiretroviral therapy (HAART) within 72 hours of exposure when the source is known to be HIV-positive or represents substantial transmission risk. 1

Timing and Eligibility

• Start PEP as soon as possible, ideally within 72 hours of exposure – the sooner treatment begins, the more likely it is to prevent HIV transmission by suppressing local viral replication before systemic infection occurs 1
• PEP is recommended for exposures to blood, genital secretions, or other potentially infected body fluids from a known HIV-positive source that represent substantial transmission risk 1
• While 72 hours is the standard window, consider initiating PEP even after 72 hours for high-risk exposures if clinical judgment suggests diminished benefit still outweighs risks 1

Preferred Regimens

The U.S. Department of Health and Human Services recommends specific three-drug HAART combinations 1:

Preferred regimens include:

• Efavirenz + lamivudine (or emtricitabine) + zidovudine or tenofovir (NNRTI-based regimen) 1
• Lopinavir/ritonavir (Kaletra) + zidovudine + lamivudine (or emtricitabine) (PI-based regimen) 1

More recent evidence supports integrase strand transfer inhibitor (INSTI)-based regimens as better tolerated alternatives, particularly those containing tenofovir with lamivudine or emtricitabine 2

Rationale for Three-Drug Therapy

• Three-drug HAART provides maximal suppression of viral replication, which is assumed to offer the best chance of preventing infection in exposed individuals 1
• While no evidence definitively proves three-drug regimens are superior to two-drug regimens for PEP, the recommendation follows the treatment standard for established HIV infection 1
• Two-drug regimens (two reverse transcriptase inhibitors) remain acceptable if adherence or toxicity concerns with three drugs are substantial 1

Source Person Considerations

When the source person is available:

• Obtain their antiretroviral medication history and most recent viral load to guide drug selection and avoid prescribing medications to which the source virus may be resistant 1
• Consider drawing blood for viral load and resistance testing if results can be obtained promptly to modify the initial PEP regimen 1

When the source person's HIV status is unknown:

• No formal recommendation exists for or against PEP 1
• Evaluate risk and benefits on a case-by-case basis, considering background HIV prevalence and local epidemiological patterns 1

Essential Concurrent Interventions

Screen and treat for sexually transmitted infections (STIs):

• Sexual exposures that risk HIV transmission also risk other STIs, which can increase HIV acquisition risk 1
• Provide prophylaxis for STIs and test for hepatitis B; vaccinate if not immune 1

Adherence and Monitoring

• Counsel patients about potential side effects and adverse events requiring immediate medical attention 1
• Consider prescribing antiemetics or antimotility agents to improve adherence if gastrointestinal side effects occur 1
• Common side effects include nausea (57%) and fatigue (38%), though most are manageable and resolve after completing treatment 1
• Approximately 76% of individuals taking PEP report some symptoms, but only 1.3% experience severe adverse events requiring discontinuation 1

Follow-Up Testing

• Perform baseline HIV testing before initiating PEP using rapid tests that provide results within 2 hours 1
• HIV testing should be voluntary with appropriate pre- and post-test counseling, but assessment should not delay PEP initiation in emergency situations 1
• Follow-up testing typically occurs at 6 weeks, 3 months, and 6 months after exposure 3

Critical Pitfalls to Avoid

• Do not delay PEP initiation for HIV testing results – start treatment immediately if exposure risk is substantial 1
• Do not use nevirapine-containing regimens – severe hepatotoxicity and skin reactions have been reported in PEP recipients 1
• Do not assume PEP replaces prevention – provide comprehensive risk-reduction counseling, as 17% of PEP recipients request repeat courses within one year, indicating ongoing risk behaviors 1

Evidence Quality Note

While the evidence base includes observational studies and case reports rather than randomized controlled trials, cumulative data from multiple sources demonstrate that antiretroviral therapy initiated soon after exposure and continued for 28 days reduces HIV acquisition risk 1. The WHO has shifted toward recommending three-drug regimens universally given improved tolerability of newer medications and the difficulty in assessing drug resistance risk 1.