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Body Changes, Toxicity, Efficacy: d4T vs Abacavir, plus 3TC/EFV
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"Toxicity and Efficacy of 3TC/EFV Associated with Stavudine or Abacavir in Antiretroviral-naive Patients: 48-week Results of a Randomized Open and Multicenter Trial (ABCDE Study)"
Reported by Jules Levin
Podzamczer et al and ABCDE Study Team (Hosp. Univ. de Bellvitge. L'Hospitalet, Barcelona, Spain) reported results at 11th Retrovirus Conference (Feb 2004).
This was a randomized, multicenter, and open-label study to evaluate lipoatrophy, other toxicities, and efficacy of two HAART PI-sparing regimens containing d4T or abacavir plus 3TC/efavirenz in treatment-naïve patients.
Both regimens were twice daily. The study setting was 17 University teaching Spanish hospitals. Patients were randomized to 3TC (150 mg bid or 300 mg QD since approval) plus EFV 600 mg daily, plus either d4T (30 or 40mg bid, according to weight) or abacavir 300 mg bid.
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.
No differences in baseline characteristics were observed between arms: average age 38; 75% men; 90% white; 30% drug users, 30% MSM, 40% heterosexual, and 21% had prior AIDS. Mean CD4 was 214/uL and mean HIV-1 RNA 5.2 log (158,000 copies/ml).
RESULTS
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 (15.1% vs 1.4%, p = 0.002), arms (11.6% vs 1.4, p = 0.011) and buttocks (10.6% vs 1.4%, p = 0.02). Clinical observations correlated with changes in anthropometric measures. For women, differences between d4T or ABC for fat accumulation in the breast was not significant, increase of 10.5% for d4T vs 2.7% for ABC.
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.
Discontinued initial regimen: 19.7% d4T, 26.1% ABC. Switch due to toxicity: 8.2%* for d4T, 15.7% for ABC**.*1 patient was lost and 1 died after switching due to toxicity. **3 patients were lost and 1died after switching due to toxicity.
No differences were found in viral load <50 copies/mL by ITT (63.9% and 64.3%) and by OT (80.4% and 87.1%). Mean CD4 count increase was similar with a gain of more than 200 cells/uL in both arms.
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. An expected greater decrease in TC:HDL and LDL:HDL was observed in ABC arm.
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