Duration of HIV Post-Exposure Prophylaxis (PEP)
PEP must be taken for exactly 28 days, with no option for early discontinuation, regardless of exposure severity or any subsequent information about the source patient. 1, 2
Standard Treatment Duration
Complete the full 28-day course of antiretroviral therapy starting from the day of initiation. 1, 2 This recommendation has remained consistent across all CDC guidelines from 1996 through 2025.
The 28-day duration is based on animal model data and represents the established standard of care, though the CDC acknowledges that prescribing a 30-day supply may be more practical for pharmacy dispensing—patients should be instructed that the course is complete after 28 days. 1
Initiate PEP as soon as possible, ideally within 24 hours of exposure, with a maximum window of 72 hours. 1, 2 Efficacy decreases dramatically with each passing hour of delay. 2
Critical Adherence Requirements
Incomplete adherence significantly reduces effectiveness—the full 28-day course must be completed even if you later learn the source patient is HIV-negative or if the exposure risk was lower than initially assessed. 2
Side effects are common (reported in 46.9% of healthcare workers taking PEP), with nausea (26.5%) and fatigue (22.8%) being most frequent. 1 However, side effects are not a reason to stop early—provide anti-emetics or other supportive medications proactively to manage symptoms. 2
The single-tablet regimen (bictegravir/emtricitabine/tenofovir alafenamide) improves completion rates compared to multi-pill regimens. 2
Follow-Up Testing Schedule After the 28-Day Course
Within 72 hours after starting PEP: Clinical evaluation and assessment for drug toxicity 2
At 4-6 weeks: HIV antigen/antibody test PLUS HIV nucleic acid test (NAT) 2, 3
At 12 weeks (3 months): Laboratory-based HIV antigen/antibody combination immunoassay AND HIV nucleic acid test (NAT)—this is the definitive timepoint to rule out HIV infection 2, 3
Test immediately if acute retroviral symptoms develop (fever, rash, lymphadenopathy, pharyngitis), regardless of timeline 2
Common Pitfalls to Avoid
Never discontinue PEP early based on source patient testing results or reassessment of exposure risk—once started, complete the full 28 days 2
Never delay the first dose for any reason, including waiting for laboratory results or specialist consultation 2
Never use two-drug regimens unless three-drug options are absolutely unavailable 2
Schedule follow-up visits or phone check-ins during the 28-day course to encourage adherence and address emerging side effects 2