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Sci Transl Med. 2017 Dec 6;9(419). pii: eaan8848. doi: 10.1126/scitranslmed.aan8848.

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

Author information

1
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
2
Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD 20892, USA.
3
Biostatistics Research Branch, NIAID, NIH, Bethesda, MD 20892, USA.
4
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
5
Department of Global Health, University of Washington, Seattle, WA 98195, USA.
6
Profectus BioSciences Inc., Tarrytown, NY 10591, USA.
7
Maple Leaf Medical Clinic, Toronto, Ontario M5G 1K2, Canada.
8
Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A1, Canada.
9
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. twchun@nih.gov.

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.

PMID:
29212716
DOI:
10.1126/scitranslmed.aan8848
[Indexed for MEDLINE]

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