What is the recommended PEP (Post-Exposure Prophylaxis) regimen for a patient exposed to HIV (Human Immunodeficiency Virus)?

Recommended HIV Post-Exposure Prophylaxis (PEP) Regimen

The preferred PEP regimen is bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single tablet once daily for 28 days, initiated immediately after exposure—ideally within 1-2 hours, but no later than 72 hours post-exposure. 1, 2, 3

Immediate Action Protocol

Start PEP immediately—do not delay for any reason, including pending laboratory results, risk assessment, or source patient testing. 1, 2, 3 Efficacy decreases dramatically with each passing hour after exposure. 2, 3

• Initiate treatment within 24 hours if possible, with an absolute maximum window of 72 hours post-exposure. 1, 2
• The first dose should be administered before any test results return. 1

Preferred Medication Regimen

First-line choice: Bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg (BIC/FTC/TAF)—one tablet once daily for exactly 28 days. 1, 2, 3 This single-tablet regimen maximizes adherence and has superior renal and bone safety compared to older regimens. 2, 3

Alternative regimen: Dolutegravir (DTG) 50mg once daily PLUS emtricitabine/tenofovir alafenamide (FTC/TAF) 200mg/25mg once daily for 28 days. 1, 2, 3

• Tenofovir disoproxil fumarate (TDF) 300mg can substitute for TAF if TAF is unavailable, though TAF is strongly preferred due to better renal safety. 2

Baseline Assessment Before First Dose

Perform these tests but do not delay the first PEP dose while waiting for results: 1, 2, 3

• Rapid or laboratory-based HIV antigen/antibody combination test. 1, 2, 3
• Add HIV nucleic acid test (NAT) if the patient received long-acting injectable PrEP in the past 12 months. 1
• Baseline renal function (creatinine, eGFR) before any tenofovir-based regimen. 3
• Review current medications for potential drug interactions. 1, 2, 3
• Test for other sexually transmitted infections at baseline. 2

Critical Duration Requirement

Complete the full 28-day course regardless of any subsequent information about the source patient. 1, 2, 3 Incomplete adherence significantly reduces effectiveness. 1, 2, 3 There is no option for early discontinuation. 2

• Provide anti-emetics or other supportive medications proactively to manage side effects like nausea and fatigue. 2
• Schedule follow-up visits or phone check-ins during the 28-day course to encourage adherence. 2

Follow-Up Testing Schedule

Within 72 hours after starting PEP: Clinical evaluation and assessment for drug toxicity. 1, 2, 3

At 4-6 weeks post-exposure: HIV antigen/antibody test PLUS HIV nucleic acid test (NAT). 1, 2, 3

At 12 weeks post-exposure: Laboratory-based HIV antigen/antibody combination immunoassay AND HIV nucleic acid test (NAT). 1, 2, 3

Immediate testing if acute retroviral symptoms develop (fever, rash, lymphadenopathy, pharyngitis), regardless of timeline. 2

Special Populations

Impaired renal function: Use tenofovir alafenamide (TAF) instead of tenofovir disoproxil fumarate (TDF) due to improved renal and bone safety profiles. 2, 3

Pregnancy: Does not preclude the use of optimal PEP regimens and should not be a reason to deny PEP, though expert consultation is advised. 2, 3

Indications for PEP

PEP is indicated when: 1

• An exposure occurred within the past 72 hours that presents substantial risk for HIV transmission
• The source has HIV without sustained viral suppression OR their viral suppression status is unknown

Substantial risk exposures include: 2

• Percutaneous injuries (needlestick) with HIV-infected blood
• Mucous membrane exposure to potentially infectious fluids (semen, vaginal secretions, rectal secretions, breast milk, cerebrospinal fluid, amniotic fluid, peritoneal fluid, synovial fluid, pericardial fluid, pleural fluid)

PEP is NOT indicated when: 2

• The exposed person is already HIV-positive
• The source is confirmed HIV-negative
• Exposure involves non-infectious fluids (tears, non-bloody saliva, urine, feces, vomitus, sputum, nasal secretions, sweat)

Counseling Requirements

• Advise the exposed person to use precautions to prevent secondary transmission during the follow-up period. 1, 2, 3
• Instruct the patient to seek immediate medical evaluation for any acute illness during follow-up, as this may indicate acute retroviral syndrome. 2, 3

Transition to PrEP After Completing PEP

Consider immediate transition from PEP to PrEP for persons with anticipated repeat or ongoing HIV exposures. 1, 2

• Perform HIV testing at completion of the 28-day PEP course before transitioning to PrEP. 1, 2

Expert Consultation Resources

For complex cases, contact the National Clinicians' Post-Exposure Prophylaxis Hotline (PEPline) at 1-888-448-4911, but do not delay PEP initiation while awaiting consultation. 3

Common Pitfalls to Avoid

• Never delay PEP for source testing or risk assessment—start immediately. 2, 3
• Never use two-drug regimens unless three-drug options are absolutely unavailable. 2
• Never discontinue PEP early based on subsequent source patient information. 1, 2
• Never fail to assess for drug interactions with the patient's current medications, especially if considering older regimens. 1, 2
• Never assume pregnancy is a contraindication to optimal PEP regimens. 2, 3

Historical Context

Older guidelines from 2001-2005 recommended zidovudine (ZDV) + lamivudine (3TC) as the basic regimen, with expanded regimens including protease inhibitors like indinavir or nelfinavir. 4 These regimens are now obsolete due to higher toxicity, lower adherence rates, and the availability of more effective single-tablet options. 2 The current CDC recommendations prioritize integrase inhibitor-based regimens (BIC/FTC/TAF or DTG-based) due to superior efficacy, safety profile, and once-daily dosing that improves completion rates. 1, 2, 3