A comparison of stavudine plus lamivudine versus zidovudine plus lamivudine in combination with indinavir in antiretroviral naive individuals with HIV infection: selection of thymidine analog regimen therapy (START I)

Background: No clinical trial results directly comparing two nucleoside ana log pairs in a drug regimen for HIV that includes a protease inhibitor are available. Objective: To compare the safety and efficacy of stavudine (d4T) + lamivudi ne (3TC) with zidovudine (ZDV) + 3TC, each in combination with indinavir (I DV). Design: Randomized, open-label, multi-center. Setting: Fifteen HIV clinical research centers. Patients: Two-hundred and four antiretroviral-naive HIV-1-infected-patients with CD4 cell counts greater than or equal to 200 x 10(6)/l and HIV-1 RNA greater than or equal to 10 000 copies/ml (bDNA assay), modified to 5000 co pies/ml. Intervention: d4T 40 mg twice a day, 3TC 150 mg twice a day plus IDV 800 mg every 8 h compared with ZDV 200 mg every 8 h (modified to 300 mg every 12 h) plus 3TC and IDV. Measurements: Primary endpoint: plasma HIV-1 RNA < 500 copies/ml. Additiona l endpoints: HIV-1 RNA less than or equal to 50 copies/ml; change from base line in HIV-1 RNA and CD4 cell counts; safety and adverse events. Results: For HIV-1 RNA, 62% of patients on d4T + 3TC + IDV and 54% of patie nts on ZDV + 3TC + IDV had < 500 copies/ml HIV RNA at weeks 40 through 48 [ 90% confidence interval, -0.204 to 0.036; P = 0.213], with 49% and 47% resp ectively achieving less than or equal to 50 copies/ml at 48 weeks (90% Cl, -0.134 to 0.096; P = 0.834). Median change in CD4 cell counts at 48 weeks w as + 227 x 10(6)/l and + 198 x 10(6)/l for the d4T- and ZDV-containing arms , respectively. The median time-weighted average change from baseline in CD 4 cell counts was significantly greater at 48 weeks in the d4T-containing a rm (142 x 10(6)/l versus 110 x 10(6)/l; P = 0.033). Serious adverse events were not significantly different between treatment arms, but there were sig nificant differences for frequency of adverse events of all severity with i ncreased nausea and vomiting in the ZDV-containing arm, and increased diarr hea and rash in the d4T-containing arm. Conclusions: These results support the choice of d4T + 3TC as a nucleoside analog pair in combination with a protease inhibitor in an initial HIV trea tment regimen. (C) 2000 Lippincott Williams & Wilkins.