A randomized factorial trial comparing 4 treatment regimens in treatment-naive HIV-infected persons with AIDS and/or a CD4 cell count <200 cells/μL in South Africa

J Infect Dis. 2010 Nov 15;202(10):1529-37. doi: 10.1086/656718. Epub 2010 Oct 13.

Abstract

Background: Few randomized trials comparing antiretroviral therapy (ART) regimens have been conducted in resource-limited settings.

Methods: In the Republic of South Africa, antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals >14 years old with a CD4 cell count <200 cells/μL or a prior AIDS diagnosis were randomized to receive efavirenz (EFV) or lopinavir/ritonavir (LPV/r) with either zidovudine (ZDV) plus didanosine (ddI) or stavudine (d4T) plus lamivudine (3TC) in an open-label, 2-by-2 factorial study and followed up for the primary outcome of AIDS or death and prespecified secondary outcomes, including CD4 cell count and viral load changes, treatment discontinuation, and grade 4 events.

Results: In total, 1771 persons were randomized and followed up for a median of 24.7 months. AIDS or death occurred in (1) 163 participants assigned EFV and 157 assigned LPV/r (hazard ratio [HR], 1.04 [95% confidence interval {CI}, 0.84-1.30]) and in (2) 170 participants assigned ZDV+ddI and 150 assigned d4T+3TC (HR, 1.15 [95% CI, 0.93-1.44]). HIV RNA levels were lower (P < .001) and CD4 cell counts were greater (P < .01) over follow-up for d4T+3TC versus ZDV+ddI. Rates of potentially life-threatening adverse events and overall treatment discontinuation were similar for d4T+3TC and ZDV+ddI; however, more participants discontinued d4T because of toxicity (12.6%) than other treatments (<5%).

Conclusion: EFV and LPV/r are effective components of first-line ART. The poorer viral and immune responses with ZDV+ddI and the greater toxicity-associated discontinuation rate with d4T+3TC suggest that these treatments be used cautiously as initial therapy.

Trial registration: ClinicalTrials.gov identifier: NCT00342355.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acquired Immunodeficiency Syndrome / complications
  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Acquired Immunodeficiency Syndrome / immunology
  • Acquired Immunodeficiency Syndrome / virology
  • Adult
  • Alkynes
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use*
  • Benzoxazines / therapeutic use*
  • CD4 Lymphocyte Count
  • Cyclopropanes
  • Didanosine / adverse effects
  • Didanosine / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • HIV / genetics
  • Humans
  • Lamivudine / adverse effects
  • Lamivudine / therapeutic use*
  • Lopinavir
  • Male
  • Pyrimidinones / therapeutic use*
  • RNA, Viral / blood
  • Ritonavir / therapeutic use*
  • South Africa
  • Stavudine / adverse effects
  • Stavudine / therapeutic use*
  • Treatment Outcome
  • Zidovudine / adverse effects
  • Zidovudine / therapeutic use*

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Pyrimidinones
  • RNA, Viral
  • Lopinavir
  • Lamivudine
  • Zidovudine
  • Stavudine
  • efavirenz
  • Didanosine
  • Ritonavir

Associated data

  • ClinicalTrials.gov/NCT00342355