A lipodystrophy syndrome (characterized by a peripheral fat loss or central fat accumulation and metabolic abnormalities) is one of the most important limiting factors for the long-term success of antiretroviral therapy. In initial reports [1–3], these alterations were associated with the prolonged administration of highly active antiretroviral therapy that included protease inhibitors. However, soon after that occasional cases were also described in patients with protease inhibitor-sparing regimens [4]. In their recent article, Saint-Marc et al. [5] demonstrated that a possible distinct syndrome, characterized mainly by peripheral fat loss (lipodistrophy) without metabolic abnormalities, can develop in patients exclusively treated with nucleoside reverse transcriptase inhibitors (NRTI). The design of the study, however, did not allow the authors to support the conclusion entirely that lipodistrophy ‘may be related to long-term NRTI therapy, particularly that including stavudine'. Cross-sectional studies are valuable for providing descriptive information about the prevalence of a disease, but they give weak evidence for casuality, which is usually established by randomized prospective studies. Patients exclusively treated with NRTI during the period of recruitment in the study by Saint-Marc et al. [5] were necessarily a highly selected population. In particular, in one of our centres, approximately 1300 patients started antiretroviral therapy exclusively with NRTI before 1997, but only 60 (5%) remained on this modality of treatment in 1999. The report by Saint-Marc et al. [5] is a small non-randomized study including a subset of 43 patients recruited exclusively in one of the five centres participating in the Inter-Lipoco study. Patients were classified in the stavudine group (n = 27) and the zidovudine group (n = 16) according to current therapy. These two groups clearly differed from one another with regard to some important characteristics that could bias the conclusions. Most of the patients in the stavudine group (17 of 27, 63%) had received previous therapy, and the reasons for changing therapy were not described. Conversely, 14 out of 16 patients in the zidovudine group (88%) were still on their initial regimen. In addition, patients in the stavudine group had been diagnosed with HIV infection much earlier (nearly one year) than patients in the stavudine group. Overall, peripheral fat wasting (lipodistrophy) was observed in 20 patients, but the total durations of the therapy in those patients were neither reported nor were they compared with the durations of therapy in those patients who did not develop lipodistrophy (n = 23). According to Fig. 1 in that study, most of the cases of lipodystrophy were diagnosed while patients were receiving a stavudine-containing regimen, but several months before the patients were recruited into the actual study. Moreover, previous therapies might have predisposed the patients in the stavudine arm to develop lipodystrophy or it is possible that the initial mild clinical signs might have been the reason for switching from a zidovudine-containing regimen. In this regard, it would be interesting to know how many cases of lipodystrophy developed among those 10 patients in whom the stavudine-containing regimen was the initial therapy. Useful and apparently well tolerated drugs such as stavudine deserve a randomized clinical study before introducing changes in current therapeutic recommendations. It is true that the duration of therapy (very strongly) and current therapy with some nucleoside analogues (marginally) have been associated with lipoatrophy, but most, if not all, of those studies have similar important flaws in their design. Santiago Morenoa Esteban Martínezb
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Oct 19, 2005
A Lüdtke + 6
Open Access
