While lipid abnormalities and lipoatrophy are
associated with highly active antiretroviral therapy (HAART) for HIV,
the problem may be less severe with the nucleoside analogue abacavir
(Ziagen, GlaxoSmithKline) than with stavudine (d4T, Zerit,
Bristol-Myers Squibb).
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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