A high HIV DNA level in PBMCs at antiretroviral treatment interruption predicts a shorter time to treatment resumption, independently of the CD4 nadir

J Med Virol. 2010 Nov;82(11):1819-28. doi: 10.1002/jmv.21907.

Abstract

This study aimed to evaluate the safety of antiretroviral treatment interruption (TI) in HIV-infected patients who started treatment based on earlier guidelines, and to identify baseline factors predictive of the time to reach fixed criteria for treatment resumption. Prospective, open-label, multicenter trial. Patients were eligible if they had a CD4 cell count >350/mm(3) and plasma HIV RNA <50,000 copies/ml when they first started antiretroviral therapy (ART); and if they had a CD4 count >450/mm(3) and stable plasma HIV RNA <5,000 copies/ml for at least 6 months prior to enrollment. The criteria for ART resumption were a CD4 cell count <300/mm(3) and/or a CDC stage B or C event. 116 patients had received ART for a median of 5.3 years. The median CD4 cell count and plasma HIV RNA values at inclusion were 809/mm(3) and 2.6 log copies/ml, respectively. Median HIV DNA load at inclusion was 2.3 log copies/10(6) peripheral blood mononuclear cells (PBMCs). Thirty-six months after TI, 63.9% of the patients had not yet reached the criteria for ART resumption, and 55.9% of patients had not resumed ART. In Cox multivariable analysis, a high HIV DNA level at TI, a low CD4 nadir, and pre-existing AIDS status were the only significant risk factors for reaching the criteria for ART resumption (hazards ratio: 2.15 (1.02-4.53), 4.59 (1.22-17.24), and 5.74 (1.60-20.56), respectively). Patients who started ART with a CD4 cell count above 350/mm(3) were able to interrupt treatment for long periods without a high absolute risk of either AIDS or severe non-AIDS morbidity/mortality. A high PBMC HIV DNA level at TI was a strong predictor for more rapid treatment resumption.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-HIV Agents* / administration & dosage
  • Anti-HIV Agents* / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • DNA, Viral / blood*
  • Drug Administration Schedule
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Leukocytes, Mononuclear / virology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Treatment Outcome

Substances

  • Anti-HIV Agents
  • DNA, Viral