What is the effectiveness of Human Immunodeficiency Virus (HIV) post-exposure prophylaxis (PEP) in preventing HIV transmission in individuals of all ages and backgrounds?

HIV Post-Exposure Prophylaxis Effectiveness

HIV post-exposure prophylaxis (PEP) is highly effective when initiated promptly, with an estimated efficacy of at least 80% in preventing HIV transmission, though no randomized controlled trials have been conducted for ethical reasons. 1

Evidence Base for PEP Efficacy

The effectiveness of PEP is supported by multiple lines of evidence, though direct proof from randomized trials in humans does not exist and likely never will due to ethical constraints. 2

Animal Studies Demonstrate Time-Dependent Efficacy

• Macaque studies show that tenofovir (PMPA) completely blocked simian immunodeficiency virus (SIV) infection when administered within 24 hours of intravenous exposure and continued for 28 days. 2
• Efficacy decreased substantially when treatment was delayed to 48 or 72 hours post-exposure. 2
• In vaginal exposure models, all animals treated within 12 or 36 hours were protected, and three of four animals treated at 72 hours were also protected. 2
• These studies reveal a narrow window of opportunity—virus reaches draining lymph nodes within 2 days and disseminates to the bloodstream by 5 days after mucosal exposure. 2

Perinatal Studies Provide Human Evidence

• Perinatal trials demonstrate that postexposure antiretroviral prophylaxis to neonates reduces HIV transmission rates to 7.7-13.1%, compared to historical placebo rates of 21%. 2
• A Ugandan trial showed transmission rates of 13.1% with nevirapine given to mother and neonate versus 25.1% with zidovudine alone. 2
• These studies confirm that postexposure prophylaxis works in humans, not just through reducing maternal viral load but through direct protection of the exposed individual. 2

Critical Timing Requirements

PEP must be initiated within 72 hours of exposure for any meaningful benefit, with effectiveness declining sharply after 24-36 hours. 2, 3

• The CDC recommends starting PEP as soon as possible, ideally within 1-2 hours of exposure. 3
• Animal data suggest PEP is probably not effective when started later than 24-36 hours post-exposure. 3
• For exposures beyond 72 hours, the CDC does not recommend PEP, though clinicians may consider it for serious exposures on a case-by-case basis if potential benefit outweighs risks. 2

Current Recommended Regimens

The CDC prioritizes integrase inhibitor-based regimens as first-line PEP due to superior tolerability and adherence compared to older zidovudine-based regimens. 4

The preferred regimens for adults and adolescents are:

• Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single-tablet regimen. 4, 3
• Dolutegravir (DTG) plus tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) or lamivudine (3TC). 4, 3
• All regimens must be continued for the full 28-day course. 2, 3

Implementation Algorithm

Step 1: Immediate Assessment (Within 72 Hours)

• Perform rapid HIV antibody or fourth-generation antigen/antibody test at point of care to rule out pre-existing infection. 4
• Do not delay PEP initiation pending any test results or source person assessment. 4
• Ensure the first dose is provided during the clinical encounter if feasible. 2

Step 2: Risk Stratification

• Determine if exposure represents substantial transmission risk (receptive anal intercourse, receptive vaginal intercourse, insertive anal intercourse, needle-sharing with known HIV-positive source). 2
• Assess HIV status of source person when possible using fourth-generation testing. 4
• If source tests negative with no clinical signs of acute HIV infection, PEP is not indicated. 4

Step 3: Initiate Treatment

• Start preferred integrase inhibitor-based regimen immediately for substantial-risk exposures within 72 hours. 2, 4
• For unknown source status with substantial-risk exposure, evaluate risks and benefits on a case-by-case basis. 2

Step 4: Follow-Up Testing Schedule

• Perform laboratory-based HIV Ag/Ab test and diagnostic HIV NAT at 4-6 weeks post-exposure (except for those who started PEP within 24 hours without missed doses). 4
• Perform both laboratory-based HIV Ag/Ab and diagnostic HIV NAT at 12 weeks post-exposure—this is considered conclusive by the CDC. 4

Post-PEP Considerations

Persons completing PEP with anticipated ongoing HIV exposure should transition immediately to pre-exposure prophylaxis (PrEP) after final HIV testing, as HIV incidence rates among PEP seekers are substantially elevated. 2

• Studies show 0.37-9% of PEP recipients acquire HIV after PEP completion, often due to re-exposure. 2
• HIV incidence among men who have sex with men seeking PEP is 70.5 per 10,000, nearly twice the overall incidence in the general MSM population. 2
• When taken as prescribed, PrEP reduces HIV acquisition risk from sex by about 99% and from injection drug use by at least 74%. 2

Critical Pitfalls to Avoid

• Never use oral fluid rapid tests in the PEP context—they are less sensitive for acute/recent infection than blood tests. 4
• Never test discarded needles or syringes for virus contamination. 4
• Antiretroviral medications can suppress viral load and delay antibody formation, potentially causing false-negative results. 4
• Do not discontinue PEP prematurely if the source is later found to be HIV-negative—complete the 28-day course once started. 3
• Evaluate persons taking PEP within 72 hours after starting and monitor for drug toxicity for at least 2 weeks. 4