Background:  Few randomized comparisons of  the incidence of lipodistrophy between PI-sparing regimens including or not stavudine (d4T) have been performed to date.

Methods:  We included in a randomized study 237 eligible patients to compare 3TC/EFV plus d4T or abacavir (ABC), both twice daily. Lipodystrophy and mitochondrial toxicity was assessed by physician and patient observation, anthropometry, blood lactate, and DEXA scans and mtDNA/nDNA in a subgroup of patients. Virological success was defined as the proportion of patients with HIV-1 RNA < 50 copies/mL at 48 weeks by ITT (NC = F) and OT analyses.

Results:  No differences in baseline characteristics were observed between arms. Most patients were white men, 29% former drug users, and 21% had prior AIDS. Mean CD4 was 214/uL and mean HIV-1 RNA 5.2 log.  After 48 weeks, a mean weight increase of more than 3 kg was observed in both arms (p <0.001). However, a moderate to severe subjective lipoatrophic feature apparent for both physicians and patients identified in at least one localization was observed in 20% of d4T patients and 2.7% in ABC patients (p = 0.001), with a significant greater frequency of fat loss in face (15% vs 1.3%, p = 0.002), arms (12% vs 1.3, p = 0.011) and buttocks (11% vs 1.3%, p = 0.02). Clinical observations correlated with changes in anthropometric measures. DEXA scans were performed at baseline and at 48 weeks in 78 patients who continued with the initial allocated regimen, showing a greater fat loss in d4T vs ABC arm:  overall (-1152 g vs +1749 g, p = 0.015), in arms (-177 g vs +136 g, p = 0.013) and in legs (-1,234 g vs +519 g, p <0.001). Fasting total cholesterol and triglycerides levels significantly increased in both arms (p <0.001). Blood lactate levels significantly increased in d4T patients (p <0.001 from baseline, and p = 0.039 comparing with ABC). mtDNA/nDNA results in a subgroup of patients are pending. Frequency of drug discontinuation due to adverse events was similar in both arms (14% vs 15%). No differences were found in viral load <50 copies/mL by ITT (63.9% and 64.3%) and by OT (76.8% and 82.2%). Mean CD4 count increase was similar with a gain of more than 200 cells/uL in both arms.

Conclusions:  After 48 weeks, d4T showed a higher rate of lipoatrophy than ABC, both combined with 3TC/EFV. No differences in virological and immunological responses were found.

Keywords: d4T, abacavir; naive patients; lipoatrophy