AIDS 2024: Final Vaccine Efficacy Results from PrEPVacc: A Phase IIb HIV Prophylactic Vaccine Trial of Two Active Regimens Each Compared to Placebo
Speaker: Eugene Ruzagira
The trial included participants aged 18 to 40 from Uganda, Tanzania, and Durban, South Africa. By 2017, vaccine candidates were prepared for clinical efficacy testing. Although interventions such as Human immunodeficiency virus (HIV) testing, early access to treatment, and Pre-Exposure Prophylaxis (PrEP) were increasing, their impact on HIV incidence remained unclear. At that time, the estimated HIV incidence was 400 person-years (pyrs). Enrollment at trial centers began using a registration code, and the overall incidence in the cohort was 2.9 per 100 pyrs.
The primary objective of the vaccine trial was to evaluate the safety and efficacy of two HIV vaccine regimens compared to a placebo. Participants were randomized into three vaccine arms: Deoxyribonucleic acid (DNA)/AIDSVAX, a vaccine arm receiving DNA, Modified Vaccinia Ankara - Chronic Mucosal Disease Resistance (MVA-CMDR), and a placebo. Additionally, participants were randomized to receive either antiretroviral medications or DNA/AIDSVAX for the primary vaccine analysis. The study aimed to enroll 1,660 participants with a target vaccine efficacy of 70%. The flexible arm was anticipated to have approximately 20 infections. The trial faced several challenges, including supply chain issues, reagent and vaccine shortages, and delays that necessitated pausing the third and fourth vaccine arms. The trial was eventually halted based on the Independent Data Monitoring Committee (IDMC) recommendation due to concerns about futility. 1,512 participants were randomized, but 213 were excluded for various reasons, resulting in 1,299 participants in the primary vaccine analysis.
The study analyzed baseline characteristics and vaccine allocation to ensure balance across the vaccine arms. The vaccines were deemed safe, with only one adverse event leading to discontinuation due to product-related reasons. A total of 30 serious adverse events were reported, including three fatalities, none of which were attributed to the vaccine. Local reactogenicity events were more frequent in the vaccine arms compared to the placebo. Vaccine efficacy results indicated 14 infections overall, with an HIV incidence rate of 1.1 per 100 pyrs. In the secondary analysis, there were 11 infections in the placebo arm and an HIV incidence of 1.4 per 100 pyrs in the vaccine arm, resulting in a hazard ratio of 3.26, similar to the primary analysis but with wide confidence intervals. The DNA-MVA arm specifically had 11 infections and an HIV incidence of 1.4 per 100 pyrs. The secondary analysis for the DNA-MVA arm revealed a lower HIV incidence in the placebo arm compared to a higher incidence in the vaccine arm.
The results of the study indicate that the proportion of participants reporting condomless sex within the last seven days remained consistent across all visits up to the end of the follow-up period. There were no significant differences in the reporting of at least one PrEP dose in the two days surrounding episodes of condomless sex. Although the target vaccine efficacy of 70% was not achieved, the placebo arm recorded five infections, while the primary vaccine analysis reported only three infections.
In conclusion, the trial's vaccines did not demonstrate a reduction in HIV infection rates. The wide confidence intervals and the low incidence of infections in the placebo arm make it challenging to assess the impact of the vaccine compared to the placebo. Follow-up measures included offering HIV counseling and testing, promoting PrEP, and facilitating referrals for care in the event of infections.
The 25th International AIDS conference (AIDS 2024). 22nd-26th July, Munich, Germany
