An open randomized controlled trial of zidovudine plus lamivudine versus stavudine plus lamivudine

Objective: To compare the antiretroviral effect and safety of zidovudine (ZDV)-lamivudine (3TC) with that of stavudine (d4T)-3TC. Methods: In an open randomized controlled trial antiretroviral therapy-naive patients who had CD4+ counts ≥ 200 × 10 6 / and plasma HIV RNA load ≥ 10 000 copies/ml were randomized to receive ZDV-3TC (200 mg three times daily and 150 mg twice daily, respectively) or d4T-3TC (40 mg and 150 mg, both twice daily). If the plasma HIV RNA level at week 8 or thereafter was > 500 copes/ml, indinavir was added at the next scheduled visit. Genotypic resistance analysis of the reverse transcriptase gene was performed at week 0 and 12. Results over 24 weeks were reported. Results: Forty-seven patients were treated (24 took ZDV-3TC; 23 took d4T-3TC). Plasma HIV RNA levels decreased from median 4.80 to 3.15 log 10 copies/ml (ZDV-3TC, P < 0.0001) and from 4.98 to 3.03 log 10 copies/ml (d4T-3TC, P < 0.0001) after 12 weeks of treatment. Indinavir was added at week 12 in 11 out of 21 patients with ZDV-3TC and in 10 out of 22 patients with d4T-3TC. Median virus load at week 24 was 2.41 log 10 and 2.29 log 10 copies/ml (P = 0.14), respectively. Seventy-five per cent (15 out of 20; ZDV-3TC) and 95% (18 out of 19; d4T-3TC) of patients had a virus load of < 500 copies/ml. Genomic evidence for 3TC resistance was found in all patients tested (11/11 ZDV-3TC and 12/12 d4T-3TC). At week 12, CD4 cell counts had increased with a median of 110 × 10 6 /l in the ZDV-3TC group (baseline, 315 × 10 6 /l) and a median of 115 × 10 6 /l in the d4T-3TC groupo (baseline 290 × 10 6 /l). At week 24, the median increases were 90 and 120 × 10 6 /l, respectively. Overall the increase of CD4+ cells was higher in the d4T-3TC group (P = 0.02). Conclusion: d4T-3TC is at least as effective as ZDV-3TC, but 3TC resistance emerged in all patients investigated. The virological response of the dual nucleoside combination is of short duration. However, after addition of indinavir the virus load could be reduced to < 500 copies/ml in the majority of patients. The increase in CD4+ cell count was significantly greater in the d4T-3TC group. To prevent 3TC resistance, the drug should not be used in regimens containing only two nucleosides, irrespective the virus load at baseline.