What is the recommended HIV post‑exposure prophylaxis regimen, timing, duration, baseline labs, and adjustments for pregnancy, breastfeeding, or impaired renal function?

HIV Post-Exposure Prophylaxis

The preferred first-line regimen is bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single daily tablet for 28 days, initiated within 72 hours of exposure (ideally within 24 hours), with baseline HIV testing and follow-up at 4-6 weeks and 12 weeks. 1

Preferred Regimen

• BIC/FTC/TAF (bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg) once daily for 28 days is the CDC's first-line recommendation due to superior renal and bone safety profiles compared to older regimens 1
• Alternative regimen: dolutegravir (DTG) 50mg once daily PLUS emtricitabine/tenofovir alafenamide (FTC/TAF) 200mg/25mg once daily for 28 days 1
• If TAF is unavailable, tenofovir disoproxil fumarate (TDF) 300mg can substitute, though TAF is strongly preferred for safety reasons 1

The single-tablet BIC/FTC/TAF formulation significantly improves adherence and completion rates compared to multi-pill regimens, which is critical since incomplete courses dramatically reduce effectiveness 1. Older regimens like zidovudine (ZDV) plus lamivudine (3TC), while historically used and associated with decreased HIV transmission risk in occupational settings, are no longer preferred due to higher side effect profiles and lower adherence rates 2.

Critical Timing Requirements

• Initiate PEP as soon as possible—ideally within 24 hours, with a maximum window of 72 hours after exposure 1
• Efficacy decreases dramatically with each passing hour; the first dose should not be delayed for any reason, including waiting for test results or risk assessment 1
• If uncertainty exists about which regimen to use, start immediately with available antiretrovirals rather than delaying 2
• Animal studies demonstrate PEP is likely ineffective when started beyond 24-36 hours, though the exact human threshold is undefined 2
• For high-risk exposures, consider initiating PEP even 1-2 weeks post-exposure, as early treatment of acute HIV infection may provide benefit 2

Baseline Assessment

Perform these tests before or immediately after starting PEP (do not delay PEP for results): 1

• Rapid or laboratory-based HIV antigen/antibody combination test (fourth-generation preferred)
• Add HIV nucleic acid test (NAT) if the patient received long-acting injectable PrEP in the past 12 months 1
• Assess for medical comorbidities, allergies, and potential drug interactions with concurrent medications 1
• Test for other sexually transmitted infections at baseline 1
• Evaluate renal function (creatinine clearance) to guide tenofovir formulation choice 1

Source patient assessment: 2

• Test known sources for HIV antibody using rapid testing when possible
• Assess risk of infection using available clinical and epidemiologic information
• Do not delay PEP initiation while awaiting source testing results 1

Duration and Adherence

• Complete the full 28-day course regardless of any subsequent information about the source patient 1
• Incomplete adherence significantly reduces effectiveness; the 28-day duration is non-negotiable 1
• Provide anti-emetics or other supportive medications proactively to manage side effects like nausea and fatigue 1
• Schedule follow-up visits or phone check-ins during the 28-day course to encourage adherence and address emerging side effects 1

Follow-Up Testing Schedule

Within 72 hours after starting PEP: 1

• Clinical evaluation and assessment for drug toxicity

At 4-6 weeks: 1

• HIV antigen/antibody test PLUS HIV nucleic acid test (NAT)

At 12 weeks: 1

• Laboratory-based HIV antigen/antibody combination immunoassay AND HIV nucleic acid test (NAT)

Extended follow-up considerations: 3

• For healthcare workers coinfected with HCV following exposure to a source coinfected with HIV and HCV, extend follow-up to 12 months
• Test immediately if acute retroviral syndrome symptoms develop (fever, rash, lymphadenopathy, pharyngitis, myalgias), regardless of timeline 1, 3

The traditional 6-month follow-up schedule (baseline, 6 weeks, 3 months, 6 months) applies when using older antibody-only tests, but modern combination antigen/antibody tests with NAT allow for the shortened 12-week protocol 3.

Special Populations

Impaired renal function: 1

• Use tenofovir alafenamide (TAF) instead of tenofovir disoproxil fumarate (TDF) due to improved renal and bone safety profiles
• TAF has minimal renal toxicity compared to TDF and is preferred for patients with any degree of renal impairment

Pregnancy: 2, 1

• Pregnancy does not preclude the use of optimal PEP regimens and should not be a reason to deny PEP
• The evaluation of risk and need for PEP should be approached as with any other person who has had an HIV exposure
• The decision to use antiretroviral drugs during pregnancy should involve discussion between the woman and her healthcare provider regarding potential benefits and risks to her and the fetus
• Expert consultation is advised for pregnant patients 1
• Older regimens like ZDV/3TC were considered probably safe for pregnant healthcare workers, though current preferred regimens should be used with appropriate counseling 2

Breastfeeding:

• While specific guidance on breastfeeding is not detailed in the most recent guidelines, the general principle is that PEP should not be withheld, and expert consultation should guide decision-making regarding continuation of breastfeeding during the 28-day PEP course

Counseling Requirements

• Advise the exposed person to use precautions to prevent secondary transmission during the follow-up period (barrier methods during sexual activity, avoid blood/tissue donation, avoid breastfeeding if applicable) 2, 1
• Instruct the patient to seek immediate medical evaluation for any acute illness during follow-up, as this may indicate acute retroviral syndrome 1
• Provide psychosocial support and address anxiety related to the exposure 4

Transition to PrEP After Completing PEP

• Consider immediate transition from PEP to PrEP for persons with anticipated repeat or ongoing HIV exposures 1
• Perform HIV testing at completion of the 28-day PEP course before transitioning to PrEP 1

Exposures Warranting PEP

PEP is indicated for: 1

• Percutaneous injuries (needlestick, sharp injuries) with blood or potentially infectious fluids
• Mucous membrane exposures to blood, semen, vaginal secretions, rectal secretions, breast milk
• Nonintact skin exposure to the above fluids
• Exposures to cerebrospinal, amniotic, peritoneal, synovial, pericardial, or pleural fluids
• Sexual assault or unprotected sexual intercourse with a known HIV-positive source 5, 6
• Needle-sharing with a known HIV-positive source 6

PEP is NOT indicated for: 1

• Exposure to non-infectious fluids: tears, non-bloody saliva, urine, feces, vomitus, sputum, nasal secretions, sweat
• When the exposed person is already HIV-positive
• When the source is confirmed HIV-negative with no recent exposure risk

Common Pitfalls to Avoid

• Never delay PEP for source testing or detailed risk assessment—start immediately and adjust later if needed 1
• Do not use two-drug regimens unless three-drug options are absolutely unavailable 1
• Do not discontinue PEP early based on subsequent source information; complete the full 28 days 1
• Do not test discarded needles or syringes for virus contamination—this is unreliable and delays care 2
• Do not withhold PEP from pregnant or breastfeeding individuals; expert consultation should occur concurrently, not as a prerequisite 2, 1