A randomized controlled trial of HIV therapeutic vaccination using ALVAC with or without Remune

OBJECTIVES: Therapeutic HIV vaccination during the time of virologic suppression may delay or blunt viral load rebound after interruption of antiretroviral therapy (ART). The use of ALVAC, to enhance cytotoxic T-lymphocyte responses, with Remune, which provides CD4 T-cell help, may induce anti-HIV responses capable of controlling viral replication. METHODS: CTN173 was a randomized, placebo-controlled double-blind study in which effectively treated HIV-infected individuals (viral load <50 copies/ml for more than 2 years) with CD4 nadir more than 250 cells/μl and current CD4 cell counts more than 500 cells/μl were randomized to receive: ALVAC with Remune, ALVAC alone or matching placebos over 20 weeks. At week 24, participants interrupted ART with intensive clinical, virologic and immunologic monitoring to week 48. RESULTS: Baseline characteristics of the 52 randomized participants were balanced between arms. Forty-eight participants who received all vaccinations interrupted ART at week 24. Median time to viral load more than 50 copies/ml tended to be greater in the two vaccine arms (24.5, 23.0 vs. 13.5 days in the placebo arm, P = 0.097 for combined vaccine groups vs. placebo), but subsequent viral load set-point was not different between groups. Significantly fewer participants in the two vaccine arms restarted ART or met CD4 criteria to do so (P = 0.024). CONCLUSION: Although ALVAC with or without Remune did not lower the viral load set-point, it tended to delay viral load rebound and was associated with a greater time to meet preset criteria to restart ART. Further investigations of those individuals who derived benefit from vaccination could provide important insights into HIV therapeutic vaccine development.