A Randomized Factorial Trial Comparing 4 Treatment Regimens in Treatment-Naive HIV-Infected Persons with AIDS and/or a CD4 Cell Count < 200 Cells/mu L in South Africa

作者：Ratsela Andrew; Polis Michael^*; Dhlomo Sibongiseni; Emery Sean; Grandits Greg; Khabo Paul; Khanyile Thandeka; Komati Stephanus; Neaton James D; Naidoo Lionel Chris David; Magongoa Daphne; Qolohle Duma; Brodine S; Lane H C; Motumi N; Radebe M; Jamuna A; Oelofse P J; Ngqakayi S; Siwisa L; Swanapoel S; Levin J; Rida W N; Morodi T; Leeuw Y; Hassim S; Malan L; Somarro H; Mokhathi T; Mokwena N; Coangae N; Khanyile T; Yokwana Z; Mabindla B

来源：Journal of Infectious Diseases, 2010, 202(10): 1529-1537.

DOI：10.1086/656718

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/mL 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 A IDS 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.

• 出版日期2010-11-15