A comparison of stavudine, didanosine and indinavir with zidovudine, lamivudine and indinavir for the initial treatment of HIV-1 infected individuals: Selection of thymidine analog regimen therapy (START II)*

Abstract

Comparison of stavudine (d4T), didanosine (ddI) and indinavir (IDV) with zidovudine (ZDV), lamivudine (3TC) and IDV in HIV-1 infected patients. Randomized, open-label. Fourteen HIV Clinical Research Centers. Two-hundred and five patients with less than 4 weeks antiretroviral treatment, naive to 3TC and protease inhibitors and with CD4 cell counts ≥ 200 × 106/l and plasma HIV-1 RNA levels ≥ 10 000 copies/ml. Stavudine 40 mg and ddI 200 mg twice daily plus IDV 800 mg every 8 h compared with ZDV 200 mg every 8 h or 300 mg twice daily, 3TC 150 mg twice daily plus IDV. The proportion of patients with plasma HIV-1 RNA levels < 500 copies/ml and ≤ 50 copies/ml and changes in CD4 cell counts were compared. In an analysis of the primary endpoint, 61% of patients on d4T + ddI + IDV and 45% of patients on ZDV + 3TC + IDV had all HIV-1 RNA values obtained between weeks 40 and 48 < 500 copies/ml [95% confidence interval (CI) for the difference between proportions, 1.7–30.3%;P = 0.038]. In an intent-to-treat analysis, the percentage of all patients randomized with all HIV-1 RNA levels < 500 copies/ml between 40 and 48 weeks were 53% for the d4T + ddI + IDV arm and 41% for the ZDV + 3TC + IDV arm (95% CI, −1.4% to 25.7%;P = 0.068). At 48 weeks 41% and 35% were ≤ 50 copies/ml for the stavudine- and ZDV-containing arms respectively (P > 0.2). The median time-weighted average increases in CD4 cells count over 48 weeks were 150 × 106/l cells for the d4T arm and 106 × 106/l cells for the ZDV arm (P = 0.001). The occurrence of serious adverse events was not significantly different between arms. The combination of stavudine, ddI and IDV resulted in potent antiretroviral effects over a 48-week period, comparable or superior to zidovudine, 3TC and IDV supporting the use of stavudine, ddI and a protease inhibitor as an initial antiretroviral treatment.