FDA-Recommended Primary Endpoint for HIV Switch Trials
The FDA recommends the proportion of patients with HIV RNA less than the lower limit of quantification at 48 weeks as the primary endpoint for HIV switch trials (Answer B).
Evidence Supporting 48-Week Endpoint
The available evidence consistently demonstrates that 48 weeks is the standard timeframe for evaluating primary efficacy endpoints in HIV switch studies:
- Multiple contemporary switch trials use HIV-1 RNA <50 copies/mL at week 48 as their primary endpoint, establishing this as the regulatory standard 1, 2, 3
- The FDA Snapshot algorithm at week 48 serves as the primary analytical approach for determining virologic suppression in switch trials 1, 2
- Non-inferiority margins are established at week 48 (typically 4% or -12%) to demonstrate that switching regimens maintains viral suppression 1, 2, 3
Why 48 Weeks Rather Than Other Timeframes
24 weeks is insufficient for demonstrating durability of viral suppression after switching antiretroviral regimens:
- While some studies assess virologic response at week 24, this serves as an interim assessment rather than the primary endpoint 1
- Guidelines recommend checking viral load 1 month after switching to ensure initial maintenance of suppression, but this does not constitute the primary efficacy endpoint 4
96 weeks represents extended follow-up beyond the primary endpoint:
- Week 96 data provides long-term durability information but is not the primary regulatory endpoint 5, 6
- Extended follow-up to 96 weeks occurs after the primary 48-week analysis is complete 5
Measuring Suppression vs. Virologic Failure
The endpoint measures HIV RNA less than the lower limit of quantification (typically <50 copies/mL), not greater than or equal to this threshold:
- The primary endpoint assesses maintenance of viral suppression, defined as HIV-1 RNA <50 copies/mL 2, 3
- Virologic failure (HIV-1 RNA ≥50 copies/mL) is measured as a secondary outcome, not the primary endpoint 2
- The proportion with HIV-1 RNA ≥50 copies/mL at week 48 is reported but represents treatment failure, not the primary efficacy measure 2
Common Pitfalls to Avoid
- Do not confuse the primary endpoint with safety monitoring timepoints: While viral load should be checked at 1 month post-switch for safety monitoring, the primary efficacy endpoint remains at 48 weeks 4
- Do not use 24-week data as definitive evidence of switch success: This timeframe is too short to establish durability of viral suppression in regulatory submissions 1
- Ensure proper use of the FDA Snapshot algorithm: This specific analytical method must be applied at the 48-week timepoint for regulatory purposes 1, 2, 3