AEGiS-15IAC: [LbOrB14] MAINTENANCE WITH TRIZIVIR (TZV) OR TZV + EFAVIRENZ (EFV) FOR 48 WEEKS FOLLOWING A 48-WEEK INDUCTION WITH TZV + EFV IN ANTIRETROVIRAL-NAÏVE HIV-1 INFECTED SUBJECTS (ESS40013)

15th International AIDS Conference

Bangkok, Thailand — July 11-July 16, 2004

[LbOrB14] MAINTENANCE WITH TRIZIVIR (TZV) OR TZV + EFAVIRENZ (EFV) FOR 48 WEEKS FOLLOWING A 48-WEEK INDUCTION WITH TZV + EFV IN ANTIRETROVIRAL-NAÏVE HIV-1 INFECTED SUBJECTS (ESS40013)

Int Conf AIDS. 2004 Jul 11-16;15:Abstract No. LbOrB14

M Markowitz¹, C Hill-Zabala², J Lang³, E DeJesus⁴, L Slater⁵, Q Liao², E R Lanier², M Shaefer²
¹Aaron Diamond AIDS Research Center, New York, United States; ²GlaxoSmithKline, Research Triangle Park, United States; ³ID Consultants, Charlotte, United States; ⁴IDC Research Initiative, Altamonte Springs, United States; ⁵University of Oklahoma, Oklahoma City, United States

BACKGROUND: ESS40013 was designed to test a 4-drug induction (I) followed by a 3-drug maintenance (M) approach to initial antiretroviral therapy (ART). This approach uses highly potent ART to rapidly reduce HIV-1 RNA (vRNA) followed by simplification to a more convenient and tolerable regimen.

METHODS: 448 ART-naïve HIV-infected subjects with vRNA >5,000 c/mL had 48-week I with TZV+EFV. 282 subjects who met criteria for M including vRNA <50 c/mL at Weeks 36 and 44 were randomized to continue TZV+EFV (n=141) or simplify to TZV alone (n=141) for 48-week M. Genotypes were done at baseline (BL) and time of virologic failure (VF). Adherence was measured by the self-reported Patient Medication Adherence Questionnaire.

RESULTS: Proportions with vRNA <50 c/mL (ITT M=F) were 79% for TZV+EFV and 77% for TZV at Week 96 (p=0.697). Noninferiority of TZV to TZV+EFV was established (95% CI: -8.6%, -5.7%). Median CD4 change from BL was 179 cells/mm³ at Week 48 and was stable in both arms through Week 96. Proportions completing 48 week M were 85% for TZV+EFV and 89% for TZV. Drug-related AEs were more commonly reported for TZV+EFV compared to TZV (15% vs. 6%) and included fatigue and dreams. Median change from BL in fasting total cholesterol was +30mg/dL at Week 48; changes from Week 48 to Week 96 were +3mg/dL for TZV+EFV and –22mg/dL for TZV. VF occurred in 16 TZV and 8 TZV+EFV subjects during M (p=0.134). There was no difference (p=0.85) in time to treatment failure. The most common treatment-emergent viral mutations during M were K103N and M184V in both arms. Overall adherence to both regimens was high; however, there was a trend for a greater proportion of subjects reporting perfect adherence to TZV compared to TZV+EFV at Week 96 (88.8% vs. 79.6%; p=0.057).

CONCLUSIONS: Simplification to TZV alone following induction with TZV+EFV maintains virologic control and immunologic response. Simplification to TZV reduces fasting lipids, reduces ART-associated AEs, and may improve adherence.

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