20   Successful Substitution of Protease Inhibitors with Efavirenz (EFV) in Patients with Undetectable Viral Loads—A Prospective, Randomized, Multicenter, Open-Label Study (DMP 049).

S. Becker*¹, A. Rachlis², J. Gill³, E. Dejesus⁴, G. Pierone⁵, L. Kirkland⁶, S. Koosian⁷, D. Farina⁸, D. Labriola⁸, N. Ruiz⁸, L. Bessen⁸, and S. Villano⁸.
¹Pacific Horizon Med. Group, San Francisco, CA;²Sunnybrook and Women's Coll. Hlth. Sci. Ctr., Toronto, ON;³Southern Alberta HIV Clin., Calgary;⁴IDC Res. Initiative, Altamonte Springs, FL;⁵Treasure Coast Infectious Disease Consultants, Vero Beach, FL;⁶The Burnside Clin., Columbia, SC;⁷Oceanview Internal Med., Long Beach, CA; and⁸DuPont Pharmaceuticals Co., Wilmington, DE.

Background:Simple, potent antiretroviral (ARV) regimens that enhance adherence and are well tolerated are needed.

Methods:Prospective, randomized, multicenter, open-label, 48-week study comparing the duration of viral load (VL) suppression of a continued PI + 2 NRTIs regimen to an EFV substitution regimen. Patients (pts) who had achieved VL<50 copies/mL (cpm) were randomized (2:1) to substitute the PI(s) with EFV 600 mg QD or to continue with their existing PI regimen; NRTIs were maintained. Virologic failure was defined as a confirmed VL >50 cpm. Except where noted, differences between groups were assessed using a Chi-square test.

Results:346 pts randomized (mean age 41 yrs; 90% male; mean duration of PI treatment 21 months [92% had received PIs>6 months]; mean baseline CD₄count 574 cells/mm³). Outcome by week 24 for 322 patients treated: (EFV substitution [n = 217] vs. continued PI(s) [n = 105]): discontinued from study (any reason), 15 (6.9%) vs. 13 (12.4%), p > 0.05; met criteria for virologic failure, 6 (3.0%) vs. 9 (10.2%), p = 0.011(Kaplan- Meier estimates of % failing at 24 weeks); viral suppression maintained (observed), 188/199 (95%) vs. 83/90 (92.2%), p > 0.05; viral suppression maintained (ITT:NC=F), 187/210 (89.0%) vs. 80/99 (81.0%), p < 0.05; mean change in CD₄count, +34 vs. +64, p > 0.05 (ANOVA); adherence (pts with missed doses on multiple visits), 21% vs. 38%, p = 0.002.

Conclusions:EFV substitution of a PI, in a suppressive PI-containing regimen, successfully maintains ARV suppression (VL<50 cpm), results in continued increases in CD₄counts, and is associated with improved adherence. This strategy may allow for improved long-term treatment success.