14th International AIDS Conference


Barcelona, Spain — July 7-12, 2002
[TITLE:] Antiretroviral strategies in naïve HIV+ subjects: comparison of 4-drug versus sequential 3-drug regimens (ACTG 384)

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

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. LbOr20B

[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 vs single 4-drug regimens (objective C).

Design: 4-drug arms: ddI+d4T+NFV+EFV (n=178); ZDV+3TC+NFV+EFV (n=182). 3-drug arms: 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) & country. 1° endpoint: time to failing a single 4-drug regimen or two sequential 3-drug regimens. Regimen failure (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: Patients were followed a median of 28 months. Median baseline CD4 278, VL 4.9 log, age 36; 72% men, 53% non-white. There was no evidence of difference in time to 1° endpoint between single 4-drug regimens compared to two sequential 3-drug regimens. 2° endpoint analysis showed that 4-drug regimens delayed time to 1st RF (HR=0.53; 0.39-0.71) and 1st VF (HR=0.45; 0.33-0.61) compared with NFV+2 NRTIs but not EFV+2NRTIs. 4-drug regimens delayed time to 1st RF (HR=0.63; 0.40-0.99) and 1st VF (HR=0.57; 0.35-0.93) compared with EFV+d4T+ddI but not EFV+ZDV+3TC. Severe or dose-modifying toxicity was lower among regimens containing ZDV+3TC compared with ddI+d4T.

CONCLUSIONS: Overall, there were no significant differences in 1° endpoint between single 4-drug and two sequential 3-drug regimens. 4-drug regimens significantly delayed 1st RF and 1st VF compared to NFV-containing 3-drug regimens regardless of NRTIs used. 4-drug regimens significantly delayed 1st RF and 1st VF compared to EFV-containing 3-drug regimens only in the ddI+d4T containing arms.

Presenting author: Robert Shafer

020707
LbOr20B

Copyright © 2002 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.