title: 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/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.
authors.affiliation: Université Paris-Descartes, EA3620 Paris, France. veronique.avettand@nck.aphp.fr
authors.forename: Véronique
authors.initials: V
authors.lastname: Avettand-Fenoel
authors.forename: Vincent
authors.initials: V
authors.lastname: Bouteloup
authors.forename: Adeline
authors.initials: A
authors.lastname: Mélard
authors.forename: Catherine
authors.initials: C
authors.lastname: Fagard
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chaix
authors.forename: Pascale
authors.initials: P
authors.lastname: Leclercq
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Viard
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use; D016879:Salvage Therapy / Q000379:methods; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D007376:Interleukin-2