[LbOr20A] Antiretroviral strategies in naïve HIV+ subjects: comparison of sequential 3-drug regimens (ACTG 384)

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Antiretroviral strategies in naïve HIV+ subjects: comparison of sequential 3-drug regimens (ACTG 384)

[AUTHOR(S):] Gregory Robbins, Robert Shafer, Laura Smeaton, Victor De Gruttola, Carla Pettinelli, Sally Snyder, Richard DAquila, Stefano Vella

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. LbOr20A

[ABSTRACT:] Introduction: 6-arm study of 980 naïve Pts. 2x3 factorial design: A. ZDV+3TC vs d4T+ddI, B. EFV vs NFV, C. 3 vs 4 drugs. This abstract compares sequential 3-drug regimens (obj. A&B).

Design: ddI+d4T+EFV→ZDV+3TC+NFV; ddI+d4T+NFV→ZDV+3TC+EFV; ZDV+3TC+EFV→ddI+d4T+NFV; ZDV+3TC+NFV→ddI+d4T+EFV (N=155/arm). NFV & EFV were blinded. Randomization and analyses were stratified by viral load(VL) and country. 1° endpoint was time to 2nd 3-drug regimen failure(RF). RF included virologic failure(VF), toxicity, or premature discontinuation. 2° endpoints: time to 1st RF or 1st VF. Hazard ratios(HR, 95% CI) from Cox regression with Bonferroni correction.

RESULTS: Pts were followed a median of 28 months. Median baseline CD4 278, VL 4.9 log, age 36; 72% men, 53% non-white. Effect of starting with ZDV+3TC vs ddI+d4T on 1° endpoint depended on whether subjects started with EFV or NFV (interaction test, p=0.02). Interaction was stronger for two 2° endpoints: time to 1st RF (p=0.002), time to 1st VF (p=0.0006), and resulted from benefits of ZDV+3TC+EFV compared to other 3-drug regimens. Analyses of 1° endpoint adjusted for two comparisons showed trend favoring starting with (a)ZDV+3TC vs (b)ddI+d4T in combination with (c)EFV (HR=0.68; 0.46-1.01) but not (d)NFV and of starting with (c) vs (d) in combination with (a) (HR=0.71; 0.48-1.06) but not (b). 2° endpoint comparisons significantly favored (a) & (c) for time to 1st RF (HR=0.35; 0.22-0.58)(HR=0.40; 0.25-0.66) and 1st VF (HR=0.39; 0.24-0.66)(HR=0.34; 0.21-0.56), respectively. Median time to severe or dose-modifying toxicity was 104 wks on ZDV+3TC arms and 52 wks on ddI+d4T arms.

CONCLUSIONS: Starting with ZDV+3TC vs ddI+d4T showed a strong trend to delay sequential RF and significantly delayed 1st RF and 1st VF when combined with EFV but not NFV. Starting with EFV vs NFV showed a strong trend to delay sequential RF and significantly delayed 1st RF and 1st VF when combined with ZDV+3TC but not d4T+ddI.

Presenting author: Gregory Robbins

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