HIV protease inhibitor substitution in patients with lipodystrophy: a randomized, controlled, open-label, multicentre study

Background: Lipodystrophy, dyslipidaemia and insulin resistance often compl icate protease inhibitor-containing antiretroviral therapy. The aims of thi s study were to determine if these are reversible with continued HIV suppre ssion following protease inhibitor substitution. Methods: Eighty-one HIV protease inhibitor recipients (78 male; mean antire troviral therapy, 55 months) with predominant peripheral lipoatrophy, HIV R NA < 400 copies/ml plasma for at least the preceding 6 months, and no prior abacavir, nonnucleoside analogue or adefovir therapy were randomized 3 : 2 to continue nucleoside analogues and substitute protease inhibitor(s) with abacavir, nevirapine, adefovir and hydroxyurea (n = 49) or to continue all therapy (n = 32) with an option to switch at week 24. The primary endpoint s were total body fat and HIV RNA at week 24. Other assessments were regime n safety, regional body composition, metabolic parameters, quality of life, and CD4 T-lymphocyte counts to week 48. Results: There was a greater decline in total body fat in the switch group than in the continue group (-1.6 and -0.4 kg, respectively at week 24; P = 0.006). This comprised greater declines in limb and subcutaneous abdominal fat, and in intraabdominal fat of patients with moderate or severe abdomina l fat accumulation. Viral suppression was similar, despite 18 (37%) switch group patients ceasing at least one study drug by week 24 because of advers e events. Total cholesterol and triglycerides declined more in the switch g roup (both P < 0.002). High density lipoprotein cholesterol increased signi ficantly in both groups at week 48 (P < 0.02). There was no change for any glycaemic parameter. Conclusions: In predominantly lipoatrophic patients, switching from HIV pro tease inhibitor therapy lead to improved lipids and less intra-abdominal fa t, but also to less peripheral fat, and had minimal effect on insulin resis tance. Virological control in these heavily pretreated patients was unaffec ted, despite frequent switch drug cessations. (C) 2001 Lippincott Williams & Wilkins.