Increased risk of lipodystrophy when nucleoside analogue reverse transcriptase inhibitors are included with protease inhibitors in the treatment of HIV-1 infection

Background: Changes in body fat distribution are an adverse effect of thera py with HIV protease inhibitors (PI). It has been suggested that nucleoside analogue reverse transcriptase inhibitors (NRTI) may also contribute to th is so-called lipodystrophy syndrome, but the relative contribution of the t wo drug classes is unclear as they are usually administered concomitantly. Method: The occurrence of lipodystrophy, as reported by physicians using no standardized criteria, was followed in patients randomly assigned to treat ment with either a PI alone or a PI combined with an NRTI. The patients wer e part of a multicenter open-label, randomized comparison of ritonavir (RTV )/saquinavir (SQV) with or without the addition of stavudine (d4T) in HIV-1 -infected patients without prior PI and d4T experience (the Prometheus stud y). Results: Lipodystrophy was reported in 29 of 175 (17%) patients during 96 w eeks of follow up. Overall, it was reported significantly more frequently i n patients who were randomized to RTV/SQV/d4T (22/88; 25%), than in patient s randomized to RTV/SQV alone (7/87; 8%) (P= 0.003). When the analysis was limited to patients without any prior antiretroviral experience, lipodystro phy likewise was significantly more frequent in patients randomized to RTV/ SQV/d4T (12/50; 24%) than in those randomized to RTV/SQV (2/44; 5%) (P= 0.0 08). Conclusion: This randomized clinical trial, in spite of not having been bli nded, supports a contributory role of NRTI in the development of antiretrov iral therapy-associated lipodystrophy. The low incidence of lipodystrophy i n patients with no or limited NRTI exposure supports further evaluation of NRTI-sparing regimens as alternatives to current antiretroviral regimens. ( C) 2001 Lippincott Williams & Wilkins.