Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study

PLoS Pathog. 2013 Mar;9(3):e1003211. doi: 10.1371/journal.ppat.1003211. Epub 2013 Mar 14.

Abstract

Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [PTCs]) whose viremia remained controlled for several years after the interruption of prolonged cART initiated during the primary infection. Most PTCs lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers (HICs); instead, they carried risk-associated HLA alleles that were largely absent among the HICs. Accordingly, the PTCs had poorer CD8+ T cell responses and more severe primary infections than the HICs did. Moreover, the incidence of viral control after the interruption of early antiretroviral therapy was higher among the PTCs than has been reported for spontaneous control. Off therapy, the PTCs were able to maintain and, in some cases, further reduce an extremely low viral reservoir. We found that long-lived HIV-infected CD4+ T cells contributed poorly to the total resting HIV reservoir in the PTCs because of a low rate of infection of naïve T cells and a skewed distribution of resting memory CD4+ T cell subsets. Our results show that early and prolonged cART may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Anti-HIV Agents / administration & dosage*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • HIV Infections / drug therapy
  • HIV Infections / prevention & control*
  • HIV Infections / virology
  • HIV Seropositivity
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Histocompatibility Testing
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral / genetics
  • Viral Load
  • Viremia / prevention & control
  • Virus Replication

Substances

  • Anti-HIV Agents
  • RNA, Viral

Grant support

The VISCONTI study (Viro-Immunological Sustained CONtrol after Treatment Interruption) was funded by the ANRS, the French National Agency for Research on AIDS and Viral Hepatitis (Grant ANRS EP47). CB and BD received predoctoral fellowships from UPMC and ANRS, respectively. CL received a postdoctoral fellowship from ANRS. GP was funded by INSERM. (http://www.anrs.fr, http://www.inserm.fr, http://www.upmc.fr). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.