[41] ACTG 5095: A COMPARATIVE STUDY OF 3 PROTEASE INHIBITOR-SPARING ANTIRETROVIRAL REGIMENS FOR THE INITIAL TREATMENT OF HIV INFECTION

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] ACTG 5095: A COMPARATIVE STUDY OF 3 PROTEASE INHIBITOR-SPARING ANTIRETROVIRAL REGIMENS FOR THE INITIAL TREATMENT OF HIV INFECTION

[AUTHOR(S):] RM Gulick¹, HJ Ribaudo², CM Shikuma³, S Lustgarten², WA Meyer⁴, K Klingman⁵, KE Squires⁶, S Snyder⁷ and DR Kuritzkes⁸
¹Cornell, New York, USA; ²Harvard School of Public Health, Boston, MA, USA; ³U Hawaii, HI, Honolulu,USA; ⁴Quest Diagnostics, Baltimore, MD, USA; ⁵Division of AIDS/NIAID/NIH, Bethesda, MD, USA; ⁶USC, Los Angeles, CA, USA; ⁷Social and Scientific Systems, Silver Spring, USA; and ⁸Harvard Medical School, Boston, MA, USA

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 41
Antiviral Therapy 2003; 8(Suppl. 1):S194

[ABSTRACT:] Objective: To compare safety/antiviral activity of three regimens for initial HIV treatment: zidovudine (ZDV)/lamivudine (3TC)/abacavir (ABC); ZDV/3TC efavirenz (EFV); ZDV/3TC/ABC+EFV.

Methods: Phase III, randomized, double-blind, placebo-controlled study of treatment-naïve HIV-infected patients (pts) with HIV RNA (VL) >400 copies/ml (c/ml). Pts were randomized 1:1:1 to ZDV/3TC/ABC (fixed dose combination, FDC); ZDV/3TC (FDC)+EFV; or ZDV/3TC/ABC (FDC)+EFV and followed for safety/virologic responses. Virologic failure (VF) was defined as confirmed VL >200 c/ml >16 weeks (wks) after randomization. VL data are presented as intent-to-treat with VF time distributions estimated using Kaplan-Meier methods. Based on a planned interim review, the NIAID Data and Safety Monitoring Board (DSMB) recommended termination of the ZDV/3TC/ABC arm; EFV-containing arms continue blinded treatment. Data are presented as ZDV/3TC/ABC vs pooled EFV-containing arms as recommended by the DSMB.

Results: 1147 pts were enrolled: 19% women, 60% non-white, 11% injection drug users. Baseline (BL) mean VL 4.9 log c/ml (43% >100,000 c/ml) and CD4 238/mm³. BL characteristics were comparable across study arms. After a median 32 wks of follow-up, 93% of pts continued on study and 91% continued study drugs. Grade 3 and 4 signs/symptoms occurred in 12% and 2%, with comparable proportions across study arms. 167 pts reached protocol-defined VF: 82 (21%) on ZDV/3TC/ABC and 85 (10%) on pooled EFV arms. Time to VF was shorter with ZDV/3TC/ABC compared to pooled EFV arms (P<0.001). This was true with BL VL > or <100,000 c/ml (P<0.001 for each). The proportion of pts with VL <200 c/ml at wk 48 was 74% (ZDV/3TC/ABC) vs 89% (pooled EFV). In a post-hoc analysis of pts with at least 1 VL <200 c/ml, time to VF also was shorter with ZDV/3TC/ABC than in pooled EFV arms (P<0.001).

Conclusions: In treatment-naïve pts, ZDV/3TC/ABC was inferior to EFV-containing treatment in terms of rates and time to virologic failure.

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