Recommended Post-Exposure Prophylaxis (PEP) Regimen for HIV Exposure
The preferred HIV PEP regimens are bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) or dolutegravir (DTG) plus tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) or lamivudine (3TC), initiated as soon as possible within 72 hours of exposure and continued for 28 days. 1
Timing of PEP Initiation
- PEP should be initiated as soon as possible after exposure, ideally within 24 hours, but no later than 72 hours 1
- Efficacy decreases with delayed initiation, as demonstrated in animal studies showing decreasing effectiveness with increasing time between exposure and antiretroviral initiation 1
- The first dose should not be delayed due to pending laboratory test results 1
Recommended PEP Regimens
Preferred Regimens for Adults and Adolescents:
- Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single-tablet regimen 1
- Dolutegravir (DTG) plus (tenofovir alafenamide [TAF] OR tenofovir disoproxil fumarate [TDF]) plus (emtricitabine [FTC] OR lamivudine [3TC]) 1
Special Populations:
- For pregnant individuals: Consider regimens with established safety data in pregnancy 2
- For individuals with renal impairment: Consider TAF-based regimens for those with creatinine clearance between 30-60 ml/min 2
- For children: Consult pediatric HIV specialists for appropriate weight-based dosing 3
Duration of PEP
- The recommended course is 28 days of continuous antiretroviral therapy 1
- The full 28-day course should be prescribed at the initial assessment 2
Laboratory Testing and Follow-up
Initial Assessment:
- Perform HIV testing using rapid (point-of-care) or laboratory-based antigen/antibody combination (Ag/Ab) test, or both 1
- For persons with long-acting injectable PrEP exposure in the past 12 months, add a diagnostic HIV nucleic acid test (NAT) 1
- Assess for medical comorbidities, current medications, and allergies 1
Follow-up Testing:
- Perform interim HIV testing with both laboratory-based HIV Ag/Ab test plus diagnostic HIV NAT at 4-6 weeks after exposure 1
- Conduct final HIV testing using laboratory-based HIV Ag/Ab combination immunoassay and diagnostic HIV NAT at 12 weeks after exposure 1
- Monitor for drug toxicity within 72 hours after starting PEP and for at least 2 weeks 1, 2
Indications for PEP
- PEP is recommended when an exposure has occurred within the past 72 hours that presents a substantial risk for HIV transmission and the source has HIV without sustained viral suppression or their viral suppression status is unknown 1
- Case-by-case determination is required when an exposure has occurred within 72 hours that presents substantial risk, but the source's HIV status is unknown 1
- PEP is not recommended if the exposure presents no substantial risk for HIV transmission 1
- PEP should be stopped if the source is found to not have HIV 1
Transition to PrEP After PEP
- Consider immediate transition from PEP to PrEP for persons with anticipated repeat or ongoing potential HIV exposures 1
- Perform HIV testing at the completion of the PEP regimen before transitioning to PrEP 1
Common Pitfalls and Caveats
- Delaying PEP initiation beyond 72 hours significantly reduces effectiveness 1
- Incomplete adherence to the full 28-day course reduces effectiveness 2
- Failure to consider drug interactions with the patient's current medications 1
- Not providing adequate follow-up for medication adherence and toxicity monitoring 1, 2
- Neglecting to counsel patients about preventing secondary transmission during the follow-up period 1
The 2025 CDC guidelines represent a significant update from earlier recommendations, moving from older regimens like zidovudine/lamivudine to newer, better-tolerated integrase inhibitor-based regimens that have demonstrated improved adherence and completion rates 4, 5.