title: Increase of HIV-1 pro-viral DNA per million peripheral blood mononuclear cells in patients with advanced HIV disease (CD4<200 cells/mm3) receiving interleukin 2 combined with HAART versus HAART alone (ANRS-082 trial).
abstract: OBJECTIVE
  To assess the effect of interleukin (IL)-2 combined with highly active antiretroviral therapy (HAART) on HIV-1 pro-viral DNA quantification in HIV-1-infected patients with CD4<200/mm3.
  
  
  METHODS
  Seventy patients with CD4<200 cells/mm3 and CV<1000 copies/ml were enrolled in a 6-month randomized controlled study to evaluate the subcutaneous injection of IL-2 in addition to HAART versus HAART alone. Then, in a non-comparative phase from week 28 to week 80, IL-2 was proposed to patients from both groups. The HIV-1 pro-viral DNA was quantified at baseline, week 24 and week 50 by a real-time polymerase chain reaction (PCR) assay in peripheral blood mononuclear cells (PBMC). Analysis of resistance mutations was performed at baseline and after 6-months of IL-2.
  
  
  RESULTS
  HIV-1 DNA level in PBMC increased significantly in patients treated with 6 months of HAART combined to IL-2 (+0.24 log10, P=0.009) compared to a slight decrease in patients treated with HAART alone (-0.05 log10). Moreover, a DNA increase was observed in control group patients when receiving 6 months of IL-2 (+0.34 log10). No increase of HIV-1 DNA was seen when this measure was expressed per million CD4 cells; it was probably hidden by the intense increase of CD4 lymphocytes after 6 months of IL-2 administration. No evolution of resistance mutations in pro-viral DNA was observed during 6 months of IL-2, despite the increase of pro-viral DNA and the occurrence of transient increase of viraemia.
  
  
  CONCLUSIONS
  Administration of IL-2 combined with HAART in HIV-1 infected-patients with advanced disease led to an increase of HIV-1 pro-viral DNA per million PBMC without virological failure or emergence of resistance.
authors.affiliation: Department of Virology-EA2387, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.forename: Karine
authors.initials: K
authors.lastname: Gourlain
authors.forename: Roland
authors.initials: R
authors.lastname: Tubiana
authors.forename: Guislaine
authors.initials: G
authors.lastname: Carcelain
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Cécile
authors.initials: C
authors.lastname: Chouquet
authors.forename: Mireille
authors.initials: M
authors.lastname: Mouroux
authors.forename: Claudine
authors.initials: C
authors.lastname: Duvivier
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood*; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D009154:Mutation
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D007376:Interleukin-2