Post-Exposure Prophylaxis (PEP) Guidelines

Introduction to PEP Regimens

The Centers for Disease Control and Prevention (CDC) recommends bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as the preferred single-tablet option for PEP, and dolutegravir plus emtricitabine/tenofovir alafenamide (DTG + FTC/TAF) as an alternative preferred regimen 1, 2
Tenofovir alafenamide (TAF) is preferred over tenofovir disoproxil fumarate (TDF) for most patients due to improved renal and bone safety profiles 2

Fostemsavir is FDA-approved only for heavily treatment-experienced adults with multidrug-resistant HIV-1, and is not recommended for PEP 3
Fostemsavir is a salvage therapy agent for patients with 3-class resistance who have failed multiple prior regimens 3

For adults and adolescents requiring PEP, initiate one of the CDC-recommended regimens within 72 hours of exposure (ideally within 1-2 hours) 1, 2
The preferred regimens are bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg (single tablet daily), and dolutegravir 50mg daily plus emtricitabine 200mg/tenofovir alafenamide 25mg (Descovy) daily 1, 2
Complete a 28-day course regardless of regimen 1, 2, 4, 5
Baseline HIV testing (antigen/antibody combination test) should be performed before initiating PEP, and follow-up HIV testing at 4-6 weeks and 12 weeks post-exposure 1, 2
Assess renal function at baseline, particularly when using tenofovir-based regimens 2

Do not delay PEP initiation while awaiting source patient testing or expert consultation—start immediately with a preferred regimen 1, 6, 7
Do not use salvage therapy agents (fostemsavir, ibalizumab) for PEP—these are reserved for treatment-experienced patients with documented resistance 3
Do not substitute TDF for TAF without considering renal function—TAF is preferred for patients with impaired renal function or bone density concerns 2
Stop PEP immediately if the source is confirmed HIV-negative during the 28-day course 1, 2

The Centers for Disease Control and Prevention recommends that PEP must be initiated within 72 hours of exposure to have any potential benefit, with optimal initiation within 1-2 hours post-exposure, and efficacy declining rapidly after 24-36 hours based on animal studies 8, 9, 10, 11
The absolute outer limit for considering PEP initiation is 1-2 weeks post-exposure, and only for the highest-risk exposures, such as receptive anal intercourse with a known HIV-positive source, or deep needlestick with a large-bore hollow needle containing HIV-positive blood 8, 9, 11

The Centers for Disease Control and Prevention recommends performing HIV antigen/antibody combination testing immediately at 1 month post-exposure, as this is the standard 4-6 week follow-up timepoint when HIV antibodies would be detectable if infection occurred 12, 13
If the HIV test is negative at 1 month, continue follow-up testing at 12 weeks post-exposure, and complete the standard 6-month follow-up testing protocol 12, 13, 11

The Centers for Disease Control and Prevention advises against prescribing antiretroviral drugs at 1 month post-exposure, as this is neither prophylaxis nor appropriate treatment, and instead, a full treatment regimen with specialist consultation and resistance testing is needed if HIV infection is confirmed 8, 9, 10, 11
If HIV testing is negative, no antiretroviral drugs are indicated, and only continued surveillance testing is necessary 12, 13