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/mu l and current CD4 cell counts more than 500 cells/mu l 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. (c) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins