HPTN 083 is an ongoing Phase 2b/3 randomized controlled trial that demonstrated superior efficacy with 66% reduced risk of HIV acquisition for long-acting injectable cabotegravir (CAB-LA) vs. daily oral TDF/FTC in the prespecified primary analysis. After unblinding in May 2020, participants continued on their original randomized study treatment until the protocol was amended and operationalized to offer eligible participants open-label CAB-LA. Fifty-one incident HIV infections were identified in the blinded trial (12 CAB, 39 TDF/FTC).
We report updated HIV incidence rates in both study arms during the blinded phase of the trial (original primary analysis period) and for one year of follow-up. Two criteria were used for incident HIV infections: detection of infection by study sites before 8/15/21; and first HIV positive visit based on site and centralized testing before 5/15/21. The primary incidence analysis prespecified exclusion of infections that occurred ?3 years after study enrollment. Safety data were updated to include events up to 5/15/21. Virology and pharmacology assays were used to characterize HIV infections.
With this one year of additional follow-up, we identified 46 additional incident HIV infections in the pre-planned analysis period (13 CAB, 33 TDF/FTC); 4 occurred during the blinded phase (2 CAB, 2 TDF/FTC), 42 after unblinding (11 CAB, 31 TDF/FTC). Reduction in risk for CAB-LA vs. FTC/TDF remained similar in blinded and unblinded phases (HR=0.33 95%CI (0.18-0.62) and HR=0.34 95%CI (0.17-0.67), Table). HIV incidence was higher in both arms in the unblinded phase, likely attributable to decreased TDF/FTC adherence, reduced CAB injection coverage, and increased relative contributions to overall person-time from high incidence regions. No new safety concerns were identified. The 2 newly-identified blinded CAB arm infections were both in the setting of on-time injections; the 11 newly-identified unblinded CAB arm infections included 1 with on-time injections, 3 with delayed injections, and 7 that occurred ?6 months after the last CAB exposure (2 of these 7 never received a CAB injection). Six additional new CAB arm infections were identified ?3 years on study (all ?6 months after the last CAB exposure).
The HRs for HIV incidence reduction for CAB-LA vs. oral TDF/FTC were consistent during one year of additional unblinded study follow-up. The correlates of CAB PrEP breakthrough are under investigation. No new safety concerns were identified.