What is the efficacy of Biktarvy (bictegravir, emtricitabine, and tenofovir alafenamide) as post-exposure prophylaxis (PEP) when initiated 64 hours after exposure?

Effectiveness of Biktarvy as Post-Exposure Prophylaxis at 64 Hours After Exposure

Biktarvy (bictegravir, emtricitabine, and tenofovir alafenamide) is not recommended for post-exposure prophylaxis (PEP) when initiated 64 hours after exposure, as PEP should be initiated within 72 hours with significantly diminishing effectiveness after 48 hours. 1

Timing of PEP Initiation and Effectiveness

The effectiveness of PEP is highly time-dependent, with animal studies showing clear evidence of decreasing efficacy as time from exposure increases:

• PEP is most effective when started as soon as possible after exposure 1, 2
• Animal studies demonstrate that efficacy decreases significantly with each day of delay:
  • 0% viral rebound when started 6 hours post-exposure
  • 20% viral rebound when started 24 hours post-exposure
  • 60% viral rebound when started 48 hours post-exposure
  • 100% viral rebound when started 72 hours post-exposure 1

At 64 hours post-exposure, the effectiveness of PEP would be severely compromised, approaching the 72-hour cutoff after which PEP is generally not recommended.

Guidelines on PEP Timing

Current CDC guidelines from 2025 are clear about timing:

• PEP should be initiated as soon as possible, but no later than 72 hours after exposure 1
• The 72-hour window was established based on non-human primate studies showing dramatically decreasing efficacy with time 1
• At 64 hours, while still technically within the 72-hour window, efficacy would be expected to be minimal based on the progressive decline in effectiveness observed in animal models 1

Biktarvy as PEP

While Biktarvy is a preferred regimen for PEP when initiated within the recommended timeframe:

• Biktarvy (BIC/FTC/TAF) is listed as a preferred regimen for adults and adolescents without contraindications 1, 2
• It has shown favorable safety, tolerability, and high completion rates (90.4%) when used for PEP 3
• Two-dose studies of FTC/TAF plus bictegravir have shown protection in animal models, but primarily when initiated pre-exposure or very early post-exposure 4

Recommendations for 64-Hour Post-Exposure Scenario

Given the 64-hour timepoint:

1. Initiate HIV testing immediately with both rapid Ag/Ab test and HIV nucleic acid test (NAT) 1

2. Consider individual risk factors:

   • Type of exposure (sexual, needlestick, etc.)
   • Source HIV status (if known)
   • Viral load of source (if known)
   • Anatomical site of exposure

3. Decision algorithm:

   • If source is known to have HIV: Consider initiating Biktarvy despite reduced efficacy
   • If source HIV status is unknown: Weigh risks and benefits on case-by-case basis
   • If exposure presents no substantial risk: PEP not recommended

Follow-up Testing

If PEP is initiated at 64 hours:

• Perform interim HIV testing at 4-6 weeks post-exposure 1
• Conduct final HIV testing at 12 weeks post-exposure using laboratory-based HIV Ag/Ab combination immunoassay and diagnostic HIV NAT 1
• Consider transition to PrEP after completing PEP if ongoing HIV risk exists 1, 2

Important Caveats

• The 72-hour cutoff is not absolute, and some experts argue that risk-benefit considerations might favor PEP beyond this window in high-risk exposures 1
• When using newer, well-tolerated regimens like Biktarvy, the risk-benefit ratio may be more favorable even with delayed initiation 1
• However, patients should be clearly informed that effectiveness is significantly reduced at 64 hours post-exposure

While Biktarvy at 64 hours is technically within the 72-hour window, its effectiveness would be severely compromised based on the progressive decline in efficacy observed with increasing time to PEP initiation.