Major influence of CD4 count at the initiation of cART on viral and immunological reservoir constitution in HIV-1 infected patients

Retrovirology. 2016 Jun 30;13(1):44. doi: 10.1186/s12977-016-0278-5.

Abstract

Background: A persistent immune activation is observed in gut during HIV-1 infection, which is not completely reversed by a combined antiretroviral therapy (cART). The impact of the time of cART initiation may highly influence the size of the viral reservoir and the ratio of CD4(+)/CD8(+) T cells in the gut. In this study, we analyzed the characteristics of HIV rectal reservoir of long-term treated patients, regarding their blood CD4(+) T cells count at the time of cART initiation.

Results: Twenty-four consenting men were enrolled: 9 exhibiting a CD4(+) T cells count >350/mm(3) ("high-level CD4 group") and 15 < 350/mm(3) ("low-level CD4 group") in blood, at the start of cART. An immunophenotypical analysis of T and B cells subpopulations was performed in blood and rectal biopsies. HIV cell-associated DNA loads and qualitative intra-cellular RNA were determined in both compartments. The ratio of CD4(+)/CD8(+) T cells was significantly decreased in the blood but not in the rectum of the "low-level CD4 group" of patients. The alteration in β7(+) CD4(+) T cells homing was higher in this group and was correlated to a low ratio of CD4(+)/CD8(+) T cells in blood. An initiation of cART in men exhibiting a low-level CD4 count was also associated with an alteration of B cells maturation. HIV blood and gut DNA reservoirs were significantly lower in the "high-level CD4 group" of men. A high HIV DNA level was associated to a detectable intracellular HIV RNA in rectum.

Conclusions: An early initiation of cART could significantly preserve gut immunity and limit the viral reservoir constitution.

Keywords: GALT; HIV; Homing; Reservoir; cART.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count*
  • CD4-CD8 Ratio
  • DNA, Viral / blood
  • Gastrointestinal Tract / immunology*
  • Gastrointestinal Tract / virology
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1* / immunology
  • HIV-1* / physiology
  • Humans
  • Male
  • RNA, Viral / isolation & purification
  • Rectum / immunology
  • Rectum / virology
  • Time-to-Treatment
  • Viral Load*

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • RNA, Viral