AN OPEN RANDOMIZED CONTROLLED TRIAL OF ZIDOVUDINE PLUS LAMIVUDINE VERSUS STAVUDINE PLUS LAMIVUDINE

Objective: To compare the antiretroviral effect and safety of zidovudi ne (ZDV)-lamivudine (3TC) with that of stavudine (d4T)-3TC. Methods: I n an open randomized controlled trial antiretroviral therapy-naive pat ients who had CD4+ counts greater than or equal to 200 x 10(6)/l and p lasma HIV RNA load greater than or equal to 10 000 copies/ml were rand omized to receive ZDV-3TC (200 mg three times daily and 150 mg twice d aily, respectively) or d4T-3TC (40 mg and 150 mg, both twice daily). I f the plasma HIV RNA level at week 8 or thereafter was > 500 copes/mi, indinavir was added at the next scheduled visit. Genotypic resistance analysis of the reverse transcriptase gene was performed at week 0 an d 12.Results over 24 weeks were reported. Results: Forty-seven patient s were treated (24 took ZDV-3TC; 23 took d4T-3TC). Plasma HIV RNA leve ls decreased from median 4.80 to 3.15 log(10) copies/mi (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 /mi (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 cel l counts had increased with a median of 110 x 10(6)/l in the ZDV-3TC g roup (baseline, 315 x 10(6)/l) and a median of 115 x 10(6)/l in the d4 T-3TC groupo (baseline 290 x 10(6)/l). At week 24, the median increase s were 90 and 120 x 10(6)/l, respectively. Overall the increase of CD4 + cells was higher in the d4T-3TC group (P = 0.02). Conclusion: d4T-3T C is at least as effective as ZDV-3TC, but 3TC resistance emerged in a ll patients investigated. The virological response of the dual nucleos ide combination is of short duration. However, after addition of indin avir the virus load could be reduced to < 500 copies/mi in the majorit y of patients. The increase in CD4+ cell count was significantly great er in the d4T-3TC group. To prevent 3TC resistance, the drug should no t be used in regimens containing only two nucleosides, irrespective th e virus load at baseline. (C) 1998 Lippincott-Raven Publishers.