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Session 101 Poster Abstracts
Antiretroviral Therapy: Regimens, Predictors of Response, and Clinical Outcomes
Thursday, 1:30 - 3:30 pm
Hall A


587    
A Randomized Comparison between Abacavir and Stavudine, both Combined with Lamivudine/Efavirenz, in Antiretroviral-Naive Patients. Final 96-Week Results of the ABCDE Study
Daniel Podzamczer*1, E Ferrer1, P Sanchez1, J Gatell2, M Crespo3, M Lonca2, J Sanz4, J Niubo5, S Veloso6, J Llibre7, P Barrufet8, M Ribas9, E Merino10, J Martínez-Lacasa11, C Alonso-Villaverde12, and ABCDE Study Group
1Hosp Univ de Bellvitge, Barcelona, Spain; 2Hosp Clin, Barcelona, Spain; 3Hosp Vall d'Hebron, Barcelona, Spain; 4Hosp Principe de Asturias, Madrid, Spain; 5Hosp Univ de Bellvitge, Barcelona, Spain; 6Hosp Joan XXIII, Tarragona, Spain; 7Hosp de Calella, Barcelona, Spain; 8Hosp de Mataro, Barcelona, Spain; 9Hosp Son Dureta, Palm de Mallorca, Spain; 10Hosp Gral de Alilcante, Spain; 11Hosp Mutua de Terrassa, Barcelona, Spain; and 12Hosp St Joan de Reus, Spain

Background:  A comparison between abacavir (ABC) and stavudine (d4T), both combined with lamivudine (3TC)/efavirenz (EFV), in the effect on lipodystrophy and lipid abnormalities, and in efficacy rates has not been performed to date. 

Methods:  We included 237 eligible HIV-infected naive patients in a randomized, open, and multicenter study comparing 3TC/EFV plus ABC or d4T, both twice daily. Lipodystrophy and mitochondrial toxicity was assessed by physician and patient observation, anthropometry, blood lactate, and DEXA scans and peripheral blood mononuclear cells (PBMC) mtDNA/nDNA in a subgroup of patients. Virological success was defined as the proportion of patients with HIV-1 RNA < 50 copies/mL by ITT (switch = failure) and OT analyses.

Results:  No differences in baseline characteristics were observed between arms. Mean CD4 was 213/µL and mean HIV-1 RNA 5.2 log. ABC was superior in virologic response by ITT (60.9% vs 47.5%, p = 0.05) but not by OT analysis (87.5% vs 85.3%, p = 0.81). Mean CD4 count increase was similar, with a gain of more than 250 cells/µL in both arms. After 96 weeks, a mean weight increase of 4.7 and 2.5 kg was observed in ABC and d4T arms, respectively (p = 0.06). A moderate to severe subjective lipoatrophic feature apparent for both physicians and patients identified in at least 1 localization was observed in 4.8% in ABC patients and 39.2% in d4T patients (p < 0.001), including face, arms, buttocks, and legs (in all, p < 0.001). Clinical observations correlated with changes in anthropometric measures. DEXA scans performed at baseline, 48 and 96 weeks in 59 patients, showed a significantly greater total limb fat loss in d4T arm: –1579 g vs +0913 g, p < 0.001. Differences in blood lactate levels were found by OT but not by ITT analyses. Changes in PBMC mtDNA/nDNA ratio between 48 and 96 weeks was evaluated in 38 patients, without significant differences between arms. D4T patients presented a greater increase in triglyceride levels (p = 0.03), a lower increase in HDLc (p < 0.001) and in ApoA1 (p < 0.001), and a lower reduction in TC:HDLc ratio (p = 0.005). Drug discontinuation (including 3TC/EFV) due to adverse events occurred in d4T arm in 33 (27%) patients (14 of 33 due to lipoatrophy) and in ABC arm in 20 (17.4%) patients (13 of 20 due to rash or hypersensitivity, including 1 due to RFB and 1 due to EFV), p = 0.075.

Conclusions:  ABC was associated with a lower rate of lipoatrophy and lipid abnormalities after 96 weeks of follow-up. In addition, the replacement of d4T, mainly due to lipoatrophy, contributed to its lower efficacy rate in the ITT, switch = failure analysis.     

Keywords: abacavir; stavudine; lipoatrophy