Higher HIV-1 DNA associated with lower gains in CD4 cell count among patients with advanced therapeutic failure receiving optimized treatment (ANRS 123--ETOILE)

J Antimicrob Chemother. 2010 Oct;65(10):2212-4. doi: 10.1093/jac/dkq282. Epub 2010 Jul 28.

Abstract

Objective: To describe HIV-1 DNA levels from baseline (W0) to week 52 (W52) among patients receiving either interleukin-2 (IL-2) + optimized background therapy (OBT) or OBT as salvage treatment.

Methods: This was evaluated in a substudy of the ETOILE Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS) 123 trial (patients with CD4 ≤ 200/mm(3), HIV RNA>4 log(10) copies/mL and a genotypic score showing two or fewer active drugs). OBT included enfuvirtide whenever possible. HIV DNA was quantified with the ANRS assay.

Results: Blood samples were available for 21 patients in the IL-2 + OBT arm and 23 in the OBT alone arm at baseline, and for 10 and 17 patients, respectively, at W52. Median baseline CD4 count was 47 cells/mm(3) and 68 cells/mm(3), respectively; median HIV RNA was 5.1 and 4.9 log(10) copies/mL. Baseline median HIV DNA load was 3.44 log(10) copies/10(6) peripheral blood mononuclear cells (PBMCs) (interquartile range 3.31-4.08) and 3.51 (3.18-3.82) log(10) copies/10(6) PBMCs, respectively. At W52, it was 3.18 log(10) copies/10(6) PBMCs (2.75-3.52) and 3.48 log(10) copies/10(6) PBMCs (3.10-3.67), respectively. Cells were available at both W0 and W52 for 7 patients in the IL-2 + OBT arm and 14 in the OBT arm. Change in HIV DNA load was not associated with IL-2 use, but decreased among the seven patients receiving enfuvirtide (-0.22 log(10) copies/mL) as compared with the other 14 patients (+0.20 log(10); P=0.046). A steeper decrease in HIV DNA was observed among patients who had a larger increase in CD4 count (Pearson coefficient ρ=0.659, P=0.001). Adjusted for enfuvirtide use, there was a trend for an association between upper baseline HIV DNA level and a less frequent CD4 gain ≥ 50 cells/mm(3) at W52 (odds ratio=0.17, P=0.075).

Conclusions: HIV DNA levels were high in patients with advanced therapeutic failure. A larger viral reservoir may be associated with lower gains in CD4 count among patients receiving OBT. HIV DNA level could be a useful tool for the case management of patients in the late stages of disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods*
  • CD4 Lymphocyte Count
  • DNA, Viral / blood
  • Follow-Up Studies
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / isolation & purification*
  • Humans
  • Interleukin-2 / therapeutic use
  • Salvage Therapy / methods
  • Treatment Failure
  • Viral Load*

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • Interleukin-2