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A randomized controlled safety/efficacy trial of therapeutic vaccination in HIV-infected individuals who initiated antiretroviral therapy early in infection

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Science Translational Medicine  06 Dec 2017:
Vol. 9, Issue 419, eaan8848
DOI: 10.1126/scitranslmed.aan8848

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Single-arm trials can leave you hanging

Depending on the study restraints and goals, not all clinical trials include a randomized placebo group. This is often done to minimize risk to patients but can also impair interpretation of the results. When Sneller et al. embarked on their therapeutic HIV vaccine trial, they chose to include a placebo group to get a better understanding of how their vaccine affected viral rebound upon therapy interruption. The vaccine itself generated minimal T cell activation and did not induce protective responses. Somewhat surprisingly, a proportion of individuals in the placebo arm demonstrated sustained viral suppression, although they were no longer being treated. These results suggest that any future HIV intervention trials would benefit from the inclusion of a placebo arm.

Abstract

Despite substantial clinical benefits, complete eradication of HIV has not been possible using antiretroviral therapy (ART) alone. Strategies that can either eliminate persistent viral reservoirs or boost host immunity to prevent rebound of virus from these reservoirs after discontinuation of ART are needed; one possibility is therapeutic vaccination. We report the results of a randomized, placebo-controlled trial of a therapeutic vaccine regimen in patients in whom ART was initiated during the early stage of HIV infection and whose immune system was anticipated to be relatively intact. The objectives of our study were to determine whether the vaccine was safe and could induce an immune response that would maintain suppression of plasma viremia after discontinuation of ART. Vaccinations were well tolerated with no serious adverse events but produced only modest augmentation of existing HIV-specific CD4+ T cell responses, with little augmentation of CD8+ T cell responses. Compared with placebo, the vaccination regimen had no significant effect on the kinetics or magnitude of viral rebound after interruption of ART and no impact on the size of the HIV reservoir in the CD4+ T cell compartment. Notably, 26% of subjects in the placebo arm exhibited sustained suppression of viremia (<400 copies/ml) after treatment interruption, a rate of spontaneous suppression higher than previously reported. Our findings regarding the degree and kinetics of plasma viral rebound after ART interruption have potentially important implications for the design of future trials testing interventions aimed at achieving ART-free control of HIV infection.

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