What is the recommended treatment for Post-Exposure Prophylaxis (PEP) therapy in a patient exposed to a potentially infectious agent, such as Human Immunodeficiency Virus (HIV)?

HIV Post-Exposure Prophylaxis (PEP) Treatment

Start bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single tablet once daily for 28 days immediately after HIV exposure, ideally within 1-2 hours but no later than 72 hours. 1, 2

Immediate Action Protocol

• Initiate PEP as soon as possible—within 1-2 hours is ideal, but must start within 72 hours maximum. 1, 2
• Do not delay the first dose while awaiting HIV testing results of either the exposed person or confirmation of the source patient's status. 1, 3
• PEP remains beneficial even when started beyond 24-36 hours, though efficacy decreases significantly with time. 1, 2
• If questions exist about which specific drugs to use, start the regimen immediately rather than delaying administration. 4

Preferred Drug Regimens

First-Line Option

• Bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg (BIC/FTC/TAF)—one tablet once daily for 28 days. 1, 2
• This single-tablet regimen simplifies adherence and is preferred due to its efficacy and tolerability profile. 2

Alternative Option

• Dolutegravir (DTG) 50mg once daily PLUS emtricitabine/tenofovir alafenamide (FTC/TAF) 200mg/25mg once daily for 28 days. 1, 2, 3
• Lamivudine (3TC) 300mg can substitute for emtricitabine if needed. 2
• Tenofovir disoproxil fumarate (TDF) 300mg can substitute for TAF if unavailable, but TAF is preferred for better renal and bone safety. 2

Regimen Selection Based on Exposure Risk

High-Risk Exposures (Require Three-Drug Regimen)

• Large-volume blood exposure, deep percutaneous injuries (not superficial), source patient with high viral load or advanced HIV disease, and exposure to concentrated virus in laboratory settings all warrant the expanded three-drug regimen. 1
• Never use only two NRTIs (like tenofovir/emtricitabine alone) for PEP—this provides inadequate protection. 2

Standard Exposures

• Most occupational HIV exposures warrant at least a two-drug nucleoside analogue regimen (e.g., ZDV and 3TC; or 3TC and d4T), though current CDC guidelines favor three-drug regimens for all indicated exposures. 4, 1

Duration and Completion

• Complete the full 28-day course if tolerated. 1, 2, 3
• The optimal duration is based on animal studies showing 4 weeks of zidovudine appeared protective. 4
• PEP may be discontinued only if the source is later confirmed to be HIV-negative. 4, 1, 2
• Incomplete adherence significantly reduces effectiveness. 2

Baseline Assessment and Testing

At Initial Presentation

• Perform rapid or laboratory-based HIV antigen/antibody combination test before starting PEP. 1, 2, 3
• Add HIV nucleic acid test (NAT) if the patient received long-acting injectable PrEP in the past 12 months. 2
• Assess baseline renal function before initiating any tenofovir-based regimen. 1, 2, 3
• Evaluate current medications for potential drug interactions, allergies, and medical comorbidities. 1, 2

Follow-Up Testing Schedule

• Reevaluate the exposed person within 72 hours post-exposure as additional information about the exposure or source person becomes available. 4, 1, 2
• Monitor for drug toxicity for at least 2 weeks after starting PEP. 1, 2
• At 4-6 weeks: Laboratory-based HIV Ag/Ab test plus diagnostic HIV NAT. 1, 2
• At 12 weeks: Laboratory-based HIV Ag/Ab combination immunoassay and diagnostic HIV NAT. 1, 2

Special Populations

Pregnant Healthcare Workers

• Approach risk assessment and need for PEP as with any other exposed person—pregnancy does not change the indication for PEP. 4, 1
• Avoid efavirenz (EFV) due to teratogenic effects observed in primate studies. 4, 1
• Avoid stavudine (d4T) plus didanosine (ddI) combination due to reports of fatal lactic acidosis in pregnant women. 4, 1
• Avoid indinavir (IDV) shortly before delivery due to risk of hyperbilirubinemia in newborns. 4
• 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 her fetus. 4

Renal Impairment

• Use tenofovir alafenamide (TAF) instead of tenofovir disoproxil fumarate (TDF) for patients with impaired renal function. 1, 2, 3

Source Patient Considerations

Known HIV-Positive Source

• Initiate PEP immediately, even when the source patient has an undetectable viral load, because occupational exposures warrant prophylaxis regardless of viral suppression status. 3
• Consider the source person's antiretroviral treatment history and potential drug resistance when selecting the PEP regimen. 4
• When the source person's virus is known or suspected to be resistant to one or more drugs, select drugs to which the virus is unlikely to be resistant; expert consultation is advised. 4

Unknown HIV Status Source

• If the source person's HIV status is unknown, decide PEP use on a case-by-case basis considering the type of exposure and clinical/epidemiologic likelihood of HIV infection in the source. 4
• If considerations suggest a possibility for HIV transmission and testing is pending, initiate the regimen until laboratory results are obtained, then modify or discontinue accordingly. 4

Critical Pitfalls to Avoid

• Never delay PEP beyond 72 hours—efficacy drops significantly with time. 1, 2
• Do not wait for source HIV testing results before starting the first PEP dose. 1, 3
• Do not use a two-drug regimen for high-risk exposures. 1
• Do not stop PEP prematurely if the source remains unknown or is confirmed positive. 1
• Never use salvage therapy agents (fostemsavir, ibalizumab) for PEP—these are reserved for treatment-experienced patients with documented resistance. 2
• Do not prescribe PEP for exposures that pose negligible risk for transmission, as the potential toxicity is not justified. 4

Expert Consultation

• Whenever possible, implement PEP regimens in consultation with persons having expertise in antiretroviral therapy and HIV transmission, but do not delay timely initiation of PEP. 4
• For complex cases or questions about drug selection, contact the National PEPline at 888-448-4911, but start PEP first without waiting for consultation. 1, 3

Counseling and Prevention of Secondary Transmission

• Provide counseling on precautions to prevent secondary transmission during the follow-up period. 1
• For persons with anticipated repeat or ongoing HIV exposures, consider immediate transition from PEP to pre-exposure prophylaxis (PrEP) after completing the 28-day course and confirming negative HIV testing. 2