These are the latest findings of the ABCDE (abacavir vs d4T plus efavirenz) Study Team, led by Dr. Daniel Podzamczer of Hospital Universitari de Bellvitge in Barcelona, Spain, and published in the February 1st issue of the Journal of Acquired Immune Deficiency Syndromes.

The investigators compared lipid profiles and the extent of lipoatrophy in 237 HIV-infected, HAART-naive adults given a regimen containing abacavir (115 patients) or stavudine (122 patients). Virologic and immunologic efficacy and tolerability of the two nucleoside analogues was also assessed in the 2-year trial.

Only 4.8% of patients on abacavir developed lipoatrophy compared with 38.3% of patients on stavudine. Dual-energy absorptiometry (DEXA) was performed in 57 patients. "There was a gain in limb fat with abacavir of 913 g vs. a fat loss of 1,579 g with stavudine," Dr. Podzamczer told Reuters Health.

Body weights were not significantly different in the two arms before or at the end of the study period.

LDL and HDL cholesterol levels increased more with abacavir than stavudine. The total/HDL cholesterol ratio dropped 1.51 with stavudine compared with a drop of 0.06 with abacavir. Triglyceride levels increased more with stavudine than abacavir.

Only 4% of patients on abacavir required lipid-lowering therapy after 2 years of treatment compared with 17% of patients on stavudine.

While stavudine and abacavir are both nucleoside analogues, they have a different mechanism of action Dr. Podzamczer told Reuters Health. "Thymidine analogues, mainly stavudine and to a lesser degree zidovudine, are associated with a higher risk of lipoatrophy than non-thymidinic nucleoside analogues such as abacavir or tenofovir, probably through a mechanism of mitochondrial toxicity."

The results "offer strong support for the concept that thymidine-analog sparing approaches are minimally associated with limb fat loss, clearly favoring the use of abacavir/lamivudine as a nucleoside backbone of the initial HAART regimen. Stavudine is no longer recommended as a first choice drug by the US Department of Health and Human Services guidelines."

The main limitation of abacavir "is a hypersensitivity reaction, observed in about 7% of patients," Dr. Podzamczer noted. "However, as we have shown in the ABCDE study, it may be manageable, even combined with efavirenz, another drug also associated in some cases with the presence of hypersensitivity."

J Acquir Immune Defic Syndr 2007;44:139-147.

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