GP120-depleted HIV-1 vaccine(The Salk Institute for Biological Studies)

To assess whether therapeutic vaccination with ALVAC-HIV ± Remune affects viral reservoir size in antiretroviral therapy-treated individuals.

Participants in CTN 173, a multicentre, randomized, 3-arm, placebo-controlled, double-blind study, were vaccinated with ALVAC-HIV ± Remune (groups 1 and 2, respectively) or with placebos (group 3) over 20 weeks and assessed for changes in the size of their viral reservoirs from weeks 0 to 24.

Sixteen participants completed the viral reservoir substudy. The median sizes (interquartile range) of the viral reservoir at baseline (week 0) were 0.07 (0.03-0.37), 0.04 (0.02-0.33), and 0.13 (0.06-0.99) infectious units per million peripheral blood mononuclear cells for groups 1, 2, and 3, respectively; these baseline viral reservoir sizes were not significantly different (P = 0.37). By week 24, the median sizes of the viral reservoirs were 0.04 (0.01-2.16), 0.04 (0.01-0.34), and 0.12 (0.01-0.44) infectious units per million peripheral blood mononuclear cells for groups 1, 2, and 3 respectively; these week 24 viral reservoir sizes were not significantly different (P = 0.91). Furthermore, there were no statistically significant differences between baseline and week 24 reservoir sizes for any of the 3 groups (P = 0.88, P = 1.00, and P = 0.44, respectively).

Despite evidence that ALVAC-HIV ± Remune was associated with a trend toward a delay in viral rebound and a smaller decrease in CD4 T-cell counts following antiretroviral therapy interruption, ALVAC-HIV ± Remune did not influence the size of the viral reservoir.

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.

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.

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).

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.