What is the recommended post-exposure prophylaxis (PEP) regimen for a patient with recent Human Immunodeficiency Virus (HIV) exposure, potentially with impaired renal function?

How to Give Post-Exposure Prophylaxis for HIV

Initiate bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single tablet once daily for exactly 28 days, starting immediately—ideally within 1-2 hours but no later than 72 hours post-exposure—without delaying for any test results or risk assessments. 1, 2

Immediate Action Protocol

Start PEP immediately upon presentation. Do not wait for:

• HIV test results from the exposed person 2
• Source patient testing or identification 2
• Risk stratification or detailed exposure assessment 2
• Specialist consultation (though available via PEPline: 1-888-448-4911) 2

Efficacy decreases dramatically with each passing hour after exposure. 1, 2 The 72-hour window is an absolute maximum; beyond this, PEP is not recommended. 1, 3

Preferred Medication Regimens

First-Line Regimen

Bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg (BIC/FTC/TAF) as one tablet once daily for 28 days. 1, 2 This single-tablet regimen offers:

• Superior renal and bone safety compared to older tenofovir formulations 1, 2
• Improved completion rates versus multi-pill regimens 1
• Better tolerability profile 2

Alternative Regimen

Dolutegravir (DTG) 50mg once daily PLUS emtricitabine/tenofovir alafenamide (FTC/TAF) 200mg/25mg once daily for 28 days. 1, 2 This is appropriate when BIC/FTC/TAF is unavailable or contraindicated.

Renal Impairment Considerations

For patients with impaired renal function, use tenofovir alafenamide (TAF) instead of tenofovir disoproxil fumarate (TDF). 1, 2 TAF has significantly better renal and bone safety profiles. 1, 2 If TAF is unavailable, TDF 300mg can be substituted, but requires closer monitoring. 1

Older Regimens (Historical Context)

The 2001 CDC guidelines recommended zidovudine (ZDV) 600mg daily plus lamivudine (3TC) 150mg twice daily as the basic regimen, with protease inhibitors added for high-risk exposures. 4 However, these regimens had completion rates as low as 39% due to side effects and complex dosing. 5 The WHO 2015 guidelines shifted to TDF + 3TC (or FTC) with lopinavir/ritonavir or atazanavir/ritonavir. 4 These older regimens should not be used when modern single-tablet options are available. 2

Baseline Assessment (Do Not Delay PEP)

Perform these assessments after initiating the first dose:

Immediate Testing

• 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, 2, 3
• Baseline renal function (creatinine, eGFR) before any tenofovir-based regimen 2
• Hepatitis B surface antigen (HBsAg) 4
• Pregnancy test in persons of childbearing potential 2
• Testing for other sexually transmitted infections 2

Clinical Assessment

• Current medications to identify drug interactions 2, 3
• Medical comorbidities and allergies 1, 2, 3
• Exposure details: type (percutaneous, mucous membrane, sexual), timing, and source characteristics 4

Critical Duration Requirement

The patient must complete the full 28-day course regardless of any subsequent information about the source patient. 1, 2, 3 There is no option for early discontinuation. 1, 2 Incomplete adherence significantly reduces effectiveness. 4, 1, 3

Adherence Support Strategies

• Provide anti-emetics or other supportive medications proactively to manage nausea and fatigue 1
• Schedule follow-up visits or phone check-ins during the 28-day course 1
• Dispense the full 28-day supply at initiation rather than "starter packs" 4
• Enhanced adherence counseling for all individuals 4

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

• Laboratory-based 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, myalgias) at any time during follow-up 4, 1

Counseling Requirements

Advise the exposed person to:

• Use barrier precautions to prevent secondary transmission during the 28-day course and follow-up period 4, 1, 2
• Seek immediate medical evaluation for any acute illness during follow-up 1, 2
• Avoid breastfeeding during PEP and follow-up if applicable 4
• Report any side effects promptly 1

Special Populations

Pregnancy

Pregnancy does not preclude the use of optimal PEP regimens and should not be a reason to deny PEP. 1, 2 Expert consultation is advised, but do not delay initiation. 1, 2 The older ZDV/3TC regimen was considered safe in pregnancy, 4 but modern regimens are preferred for efficacy.

Children ≤10 Years

• ZDV + 3TC is the preferred backbone 4
• Lopinavir/ritonavir (LPV/r) is the preferred third drug 4
• Age-appropriate alternatives include atazanavir/ritonavir, raltegravir, darunavir, efavirenz, or nevirapine 4

Adolescents and Adults >10 Years

• Use the same regimens as adults (BIC/FTC/TAF or DTG + FTC/TAF) 4, 1, 2

Indications for PEP

PEP is indicated when:

• Exposure occurred within the past 72 hours 1, 2, 3
• Exposure presents substantial risk for HIV transmission (percutaneous injury with HIV-infected blood, mucous membrane exposure to blood/semen/vaginal secretions/rectal secretions, sexual assault) 4, 2, 3
• Source has HIV without sustained viral suppression OR viral suppression status is unknown 2, 3

PEP is NOT indicated when:

• Exposed person is already HIV-positive 2
• Source is confirmed HIV-negative 2
• Exposure involves non-infectious fluids (tears, non-bloody saliva, urine, feces, vomitus, sputum, nasal secretions, sweat) 2
• More than 72 hours have elapsed since exposure 1, 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, 3 Perform HIV testing at completion of the 28-day PEP course before transitioning. 1, 2, 3

Common Pitfalls to Avoid

• Never delay PEP initiation for source testing, risk assessment, or baseline laboratory results 2, 3
• Never use two-drug regimens unless three-drug options are absolutely unavailable 2, 3
• Never discontinue PEP early based on subsequent source patient information 2
• Never fail to assess for drug interactions with the patient's current medications 2, 3
• Never prescribe older regimens (ZDV/3TC, stavudine-containing regimens) when modern single-tablet options are available 4, 1, 2

Expected Side Effects and Management

With BIC/FTC/TAF, common side effects include:

• Nausea (mild to moderate, manageable with anti-emetics) 1
• Headache 1
• Fatigue 1

Research with similar regimens (TDF/FTC/rilpivirine, elvitegravir/cobicistat/TDF/FTC) showed 69-86% of patients reported at least one adverse event, mostly mild to moderate, with premature discontinuation rates of only 4-7%. 6, 5, 7 No serious adverse events, hepatic toxicity, or renal toxicity occurred in these studies. 6