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

Andrew Ratsela, Michael A. Polis, Sibongiseni Dhlomo, Sean Emery, Greg Grandits, Paul Khabo, Thandeka Khanyile, Stephanus Komati, James D. Neaton, Lionel Chris David Naidoo, Daphne Magongoa, Duma Qolohle

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1529-1537
Number of pages9
JournalJournal of Infectious Diseases
Volume202
Issue number10
DOIs
StatePublished - Nov 15 2010

Bibliographical note

Funding Information:
We thank the entire Phidisa staff, as well as the participants who devoted their time and effort to this research project. We also acknowledge the following specialist consultants: ClinDev, which provided regulatory monitoring; Science Applications International Corporation and Bio Analytical Research Corporation, which provided laboratory and personnel support; and the Henry Jackson Foundation, which provided project and personnel support.

Funding Information:
Role of the funding source. The study was supported by SANDF, the US NIAID, and the US Department of Defense. None of these entities nor their employees or contractors had any financial interest in the drugs used. Employees and contractors of these agencies participated in study design, data

Funding Information:
Collaborators contributed to the study from the South Africa Medical Health Services (SAMHS), South African Defence Force, Pretoria, South Africa; the US National Institute of Al- lergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH), Bethesda, Maryland; the Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland; Charisma Health, Pretoria, South Africa; the University of Minnesota, Minneapolis; the National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia; the Science Applications International Corporation (SAIC), Frederick, Maryland; Palladian Partners, Inc, Silver Spring, Maryland; the KwaZulu-Natal Department of Health, Pietermaritzburg, South Africa; and the US Department of Defense (US DoD), Washington, DC.

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