What is the recommended duration for prophylactic Highly Active Antiretroviral Therapy (HAART) treatment after Human Immunodeficiency Virus (HIV) exposure?

Duration of Prophylactic HAART Treatment After HIV Exposure

The recommended duration for prophylactic HIV post-exposure prophylaxis (PEP) is 28 days, regardless of the type or severity of exposure. 1

Timing of PEP Initiation

• PEP should be initiated as soon as possible after exposure, ideally within hours
• Maximum window for starting PEP is 72 hours after exposure
• Efficacy decreases as time from exposure increases
• Optimal window is within the first 24 hours 2
• PEP should not be delayed while waiting for HIV test results of the source person

Recommended Regimens

The CDC's 2025 guidelines recommend the following preferred regimens for adults and adolescents:

• First choice: Bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF) 1
• Alternative: Dolutegravir (DTG) plus (tenofovir alafenamide [TAF] OR tenofovir disoproxil fumarate [TDF]) plus (emtricitabine [FTC] OR lamivudine [3TC]) 1

Follow-up Testing and Monitoring

• Initial follow-up: 3-7 days after starting medication to assess tolerance 2
• HIV testing:
  • Interim testing with laboratory-based HIV Ag/Ab test plus diagnostic HIV NAT at 4-6 weeks after exposure 1
  • Final HIV testing with laboratory-based HIV Ag/Ab combination immunoassay and diagnostic HIV NAT at 12 weeks after exposure 1

Important Considerations

• The 28-day duration recommendation is based on animal data and has been the standard of care for many years 1
• While newer animal model data suggest a shorter PEP course might be effective (especially if initiated <24 hours from exposure), no human data are currently available to support changing the standard 28-day course 1
• Some clinicians may prescribe a 30-day course for practical dispensing purposes, but patients should be instructed that the course is complete after 28 days 1

Special Populations and Situations

• PEP should not be withheld due to pregnancy 2
• Sexual assault survivors should receive a three-drug antiretroviral regimen for 28 days if within the 72-hour window 2
• For persons with anticipated repeat or ongoing HIV exposures, consider transition from PEP to PrEP after completion of the 28-day PEP regimen 1

Common Side Effects and Adherence

• Common side effects include nausea (26.5%) and fatigue (22.8%) 2
• Supportive medications (e.g., anti-nausea medications) may be prescribed to help manage side effects 2
• Adherence to the full 28-day regimen can be challenging, with studies showing 17-47% of individuals not completing the full course 2

The 28-day duration for PEP remains the standard recommendation despite limited direct evidence for this specific timeframe. While ongoing research may eventually lead to shorter regimens, current guidelines from the CDC and other authoritative bodies consistently recommend the 28-day course for optimal protection against HIV infection following exposure.