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)

Antivir Ther. 2003 Jun;8(3):233-7.

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.

Patients and 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.

Conclusion: 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.

Publication types

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

MeSH terms

  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active*
  • CD4 Lymphocyte Count
  • DNA, Viral / blood*
  • Drug Resistance, Viral / genetics
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification*
  • Humans
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / therapeutic use*
  • Leukocytes, Mononuclear / virology*
  • Male
  • Mutation

Substances

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