Factors associated with viral rebound in HIV-1-infected individuals enrolled in a therapeutic HIV-1 gag vaccine trial. Academic Article uri icon

Overview

abstract

  • BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) vaccines directed to the cell-mediated immune system could have a role in lowering the plasma HIV-1 RNA set point, which may reduce infectivity and delay disease progression. METHODS: Randomized, placebo-controlled trial involving HIV-1-infected participants who received a recombinant adenovirus serotype 5 (rAd5) HIV-1 gag vaccine or placebo. Sequence-based HLA typing was performed for all 110 participants who initiated analytic treatment interruption (ATI) to assess the role of HLA types previously associated with HIV prognosis. Plasma HIV-1 gag and pol RNA sequences were obtained during the ATI. Virologic endpoints and HLA groups were compared between treatment arms using the 2-sample rank sum test. A linear regression model was fitted to derive independent correlates of ATI week 16 plasma viral load (w16 PVL). RESULTS: Vaccinated participants with neutral HLA alleles had lower median w16 PVLs than did vaccinated participants with protective HLA alleles (P = .01) or placebo participants with neutral HLA alleles (P = .02). Factors independently associated with lower w16 PVL included lower pre-antiretroviral therapy PVL, greater Gag sequence divergence from the vaccine sequence, decreased proportion of HLA-associated polymorphisms in Gag, and randomization to the vaccine arm. CONCLUSIONS: Therapeutic vaccination with a rAd5-HIV gag vaccine was associated with lower ATI week 16 PVL even after controlling for viral and host genetic factors. CLINICAL TRIALS REGISTRATION: NCT00080106.

authors

  • Wilkin, Timothy
  • Li, Jonathan Z
  • Brumme, Zabrina L
  • Brumme, Chanson J
  • Wang, Hongying
  • Spritzler, John
  • Robertson, Michael N
  • Lederman, Michael M
  • Carrington, Mary
  • Walker, Bruce D
  • Schooley, Robert T
  • Kuritzkes, Daniel R

publication date

  • April 1, 2011

Research

keywords

  • AIDS Vaccines
  • HIV Infections
  • HIV-1
  • Immunotherapy
  • Vaccination
  • Viral Load

Identity

PubMed Central ID

  • PMC3068025

Scopus Document Identifier

  • 79953018441

Digital Object Identifier (DOI)

  • 10.1093/infdis/jiq143

PubMed ID

  • 21402549

Additional Document Info

volume

  • 203

issue

  • 7