Combined ART started during acute HIV infection protects central memory CD4+ T cells and can induce remission

J Antimicrob Chemother. 2015 Jul;70(7):2108-20. doi: 10.1093/jac/dkv084. Epub 2015 Apr 21.

Abstract

Background: Therapeutic control of HIV replication reduces the size of the viral reservoir, particularly among central memory CD4+ T cells, and this effect might be accentuated by early treatment.

Methods: We examined the effect of ART initiated at the time of the primary HIV infection (early ART), lasting 2 and 6 years in 11 and 10 patients, respectively, on the HIV reservoir in peripheral resting CD4+ T cells, sorted into naive (TN), central memory (TCM), transitional memory (TTM) and effector memory (TEM) cells, by comparison with 11 post-treatment controllers (PTCs).

Results: Between baseline and 2 years, CD4+ T cell subset numbers increased markedly (P < 0.004) and HIV DNA levels decreased in all subsets (P < 0.009). TTM cells represented the majority of reservoir cells at both timepoints, T cell activation status normalized and viral diversity remained stable over time. The HIV reservoir was smaller after 6 years of early ART than after 2 years (P < 0.019), and did not differ between PTCs and patients treated for 6 years. One patient, who had low reservoir levels in all T cell subsets after 2 years of treatment similar to the levels in PTCs, spontaneously controlled viral replication during 18 months off treatment.

Conclusions: Early prolonged ART thus limits the size of the HIV reservoir, protects long-lived cells from persistent infection and may enhance post-treatment control.

Keywords: HIV DNA; post-treatment controllers; primary HIV infections; reservoirs.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods*
  • CD4-Positive T-Lymphocytes / immunology*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • Humans
  • Immunophenotyping
  • Male
  • Middle Aged
  • Secondary Prevention / methods*
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Retroviral Agents