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Session 92 Poster Session Switch Studies/Treatment of Lipodystrophy Syndromes Session Time: 4:30-6:30 pm Room 4E-F

701-T. Improvements in Lipoatrophy (LA) Are Observed after 24 Weeks when Stavudine (d4T) Is Replaced by Either Abacavir (ABC) or Zidovudine (ZDV) G. McComsey*1, T. Lonergan2, R. Fisher3, M. Sension4, C. Hoppel1,5, V. Williams3, L. Ross3, and J. Hernandez3 1Case Western Reserve, Cleveland, OH; 2Univ. of California, San Diego; 3GlaxoSmithKline, Res. Triangle Park, NC; 4North Broward Hosp. District, Ft. Lauderdale, FL; and 5Louis Stokes VA Med. Ctr., Cleveland, OH Background: Lipodystrophy (LD) has been associated with ART, mainly fat accumulation with PI use and fat wasting with NRTIs. Like other ART-related metabolic disorders, this may be linked to mitochondrial toxicity. Several randomized trials and cohort studies have shown a greater risk with d4T over other NRTIs for these complications. ESS40010 is a 48-week, open-label switch study designed to assess the regression of LD, specifically LA and hyperlactatemia (HL) when ABC or ZDV was substituted for d4T in symptomatic subjects. Methods: Subjects with HIV-1 RNA <400 copies/mL on d4T-based regimens for >6 months, with LA, symptomatic HL, or both were enrolled. Self-reports, DXA, CT, anthropometric measurements, and lab values were used to assess changes. Subjects substituted ABC or ZDV (as Combivir) for d4Tat day 1. A biopsy substudy of 16 subjects was analyzed for mitochondrial functional changes in muscle, fat and blood. The intent-to-treat (ITT) population was used (all enrolled subjects with at least one post-baseline measurement). Results: 118 subjects enrolled; 86 replaced d4T with ABC and 32 with ZDV. 84% and 82% respectively entered with exam or self-reports of LA. A combined analysis at week 24 showed an increase in median percent regional fat demonstrated by DXA; arms: 27.1%, legs: 7.9%, trunk: 9.1%. There were changes in self-reports of body fat (% of subjects reporting gains of some or a lot): arms: 19.2%, legs: 19.2%, buttocks: 11%, face: 26%. For subjects with HL, the median lactate levels at screening, ART reinitiation and week 24 were 2.9, 2.1, and 1.6 mmol/L. 94% of subjects maintained HIV-1 RNA <400 copies/mL at week 24 (ITT, observed rates). Mitochondrial respiratory chain dysfunction was noted in 7/16 subjects at baseline, the most consistent being a decrease in complexes I, II and III, as well as decreased citrate synthase reflecting a quantitative mitochondrial functional loss. Conclusions: Subjects with LA showed early improvements at week 24 while maintaining virologic control when d4T was replaced by either ABC or ZDV.

©2002 9th Conference on Retroviruses and Opportunistic Infections