July 14, 2003
The Tarheel study evaluated the strategy of substituting either AZT (ZDV, zidovudine, Retrovir) or abacavir (ABC, Ziagen) for d4T (stavudine, Zerit) in patients with lipoatrophy, elevated lactate, or both. As presented previously at several scientific meetings and subsequently published, the study demonstrated a significant improvement in subcutaneous fat as measured by DEXA and CT scan, as well as self-reported improvements in lipoatrophy. Since not all patients experienced improvements, this analysis of data from the study sought to evaluate potential predictors of a patient's response to the substitution.
Out of 118 subjects, 86 replaced d4T with abacavir, and 32 with AZT. Abacavir was used if participants were AZT experienced. In general, both increases in subcutaneous fat and reductions in visceral adipose tissue were greater for the abacavir than the AZT-treated patients. Although the net changes in fat were relatively small, they were statistically significant and occurred in most of the patients: 79 percent had an increase in subcutaneous fat, while 54 percent had decreased visceral adipose tissue. In a multivariate model of several clinical and demographic factors (including age, gender, duration of overall ART and d4T use), only an elevation in the pre-study lactate level and a large volume of visceral adipose tissue were predictive of reductions in visceral adipose tissue after the substitution. A baseline higher body mass index was predictive of increases in subcutaneous adipose tissue after the substitution.
What are the implications of this study for patient management? In practice, many clinicians have already adopted a relatively low threshold after which to substitute an NRTI for d4T in patients with lipoatrophy, especially since the therapeutic options for this frustrating condition are so limited. Most of the time this is done either with abacavir, as shown in this and other studies, or with tenofovir (TDF, Viread), though studies evaluating the latter approach have not yet been presented or published.
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