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

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/mm3, HIV RNA>4 log10 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/mm3 and 68 cells/mm3, respectively; median HIV RNA was 5.1 and 4.9 log10 copies/mL. Baseline median HIV DNA load was 3.44 log10 copies/106 peripheral blood mononuclear cells (PBMCs) (interquartile range 3.31-4.08) and 3.51 (3.18-3.82) log10 copies/106 PBMCs, respectively. At W52, it was 3.18 log10 copies/106 PBMCs (2.75-3.52) and 3.48 log10 copies/106 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 log10 copies/mL) as compared with the other 14 patients (+0.20 log10; 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/mm3 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. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.