Interleukin-7 promotes HIV persistence during antiretroviral therapy

Blood. 2013 May 23;121(21):4321-9. doi: 10.1182/blood-2012-11-465625. Epub 2013 Apr 15.

Abstract

HIV persists in latently infected memory CD4(+) T cells during antiretroviral therapy (ART). When administered to HIV-infected subjects receiving suppressive ART, interleukin-7 (IL-7) increases the number of CD4(+) T cells by promoting their survival and proliferation. However, little is known about the impact of IL-7 on HIV persistence during ART. By isolating large numbers of CD4(+) T cells from HIV-infected subjects, we demonstrate that IL-7 enhances viral production in productively infected cells but does not disrupt viral latency in latently infected cells. When administered to virally suppressed subjects, IL-7 led to the rapid proliferation of memory CD4(+) T cells, which resulted in a 70% increase in the absolute number of circulating CD4(+) T cells harboring integrated HIV DNA 4 weeks after therapy. The genetic diversity of the viral reservoir increased transiently in the majority of the subjects studied before returning to baseline values. Altogether, our results indicate that IL-7 promotes the mechanisms of HIV persistence during ART by enhancing residual levels of viral production and inducing proliferation of latently infected cells, and suggest that IL-7 does not represent a suitable candidate therapeutic strategy for HIV eradication. This trial was registered at www.clinicaltrials.gov as #NCT00099671 (AIDS Clinical Trials Group protocol 5214).

Publication types

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

MeSH terms

  • Anti-Retroviral Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • Cell Division / immunology
  • Cells, Cultured
  • Genetic Variation / drug effects
  • Genetic Variation / immunology
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Humans
  • Immune Tolerance / immunology
  • Immunologic Memory / drug effects
  • Immunologic Memory / immunology
  • Interleukin-7 / immunology*
  • Interleukin-7 / pharmacology
  • Virus Latency / drug effects
  • Virus Latency / genetics
  • Virus Latency / immunology*

Substances

  • Anti-Retroviral Agents
  • IL7 protein, human
  • Interleukin-7

Associated data

  • ClinicalTrials.gov/NCT00099671