Relationship of HIV reservoir characteristics with immune status and viral rebound kinetics in an HIV therapeutic vaccine study

AIDS. 2014 Nov 28;28(18):2649-57. doi: 10.1097/QAD.0000000000000478.

Abstract

Objectives: The objective of this study is to evaluate the impact of therapeutic HIV vaccination on the HIV reservoir and assess the relationship of the viral reservoir with HIV-specific immune status and viral rebound kinetics.

Design: A retrospective analysis of ACTG A5197, a randomized, placebo-controlled trial of a therapeutic rAd5 HIV-1 gag vaccine.

Methods: Participants received vaccine/placebo at weeks 0, 4 and 26 prior to a 16-week analytic treatment interruption (ATI) at week 38. Cell-associated HIV-1 RNA and DNA (CA-RNA and CA-DNA) and HIV-1 residual viremia were quantified at weeks 0, 8 and 38. HIV-specific CD4(+)/CD8(+) activity was assessed by an intracellular cytokine staining assay.

Results: At study entry, CA-RNA and CA-DNA levels were correlated inversely with the numbers of HIV-specific CD4(+) interferon-γ producing cells (CA-RNA: r = -0.23, P = 0.03 and CA-DNA: r = -0.28, P < 0.01, N = 93). Therapeutic HIV vaccination induced HIV-specific CD4(+) activity, but did not significantly affect levels of CA-RNA or CA-DNA. Vaccine recipients with undetectable residual viremia at week 8 had higher frequencies of HIV-specific CD4(+) and CD8(+) interferon-γ producing cells (undetectable versus detectable residual viremia: 277 versus 161 CD4(+) cells/10(6) lymphocytes, P = 0.03 and 1326 versus 669 CD8(+) cells/10 lymphocytes, P = 0.04). Pre-ATI CA-RNA and CA-DNA were associated with post-ATI plasma HIV set point (CA-RNA: r = 0.51, P < 0.01 and CA-DNA: r = 0.47, P < 0.01).

Conclusion: Vaccine-induced T-cell responses were associated with a modest transient effect on residual viremia, but more potent immune responses and/or combination treatment with latency-reversing agents are needed to reduce the HIV reservoir. HIV reservoir measures may act as biomarkers of post-ATI viral rebound kinetics.

Clinical trials registration: NCT00080106.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / therapeutic use*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cytokines / biosynthesis
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • HIV Infections / immunology*
  • HIV Infections / therapy
  • HIV Infections / virology*
  • HIV-1 / immunology*
  • HIV-1 / isolation & purification*
  • Humans
  • Leukocytes, Mononuclear / virology
  • Placebos / administration & dosage
  • RNA, Viral / analysis
  • RNA, Viral / genetics
  • Retrospective Studies
  • Viral Load*
  • Viremia / virology

Substances

  • AIDS Vaccines
  • Cytokines
  • DNA, Viral
  • Placebos
  • RNA, Viral

Associated data

  • ClinicalTrials.gov/NCT00080106