Disorders of lipid metabolism in patients with HIV disease treated with antiretroviral agents: Frequency, relationship with administered drugs, and role of hypolipidaemic therapy with bezafibrate

Objectives: To assess the correlation between antiretroviral treatment and dyslipidaemia in HIV-infected patients, and the role of bezafibrate as a li pid-lowering agent. Methods: We retrospectively compared serum lipid levels of five groups of 4 0 patients, each of them treated with either saquinavir hard gel, indinavir , or ritonavir (associated with two nucleoside analogues), or dual nucleosi de reverse transcriptase inhibitors (NRTI) with or without a non-nucleoside reverse transcriptase inhibitor (NNRTI), or not treated with antiretrovira ls, randomly selected from nearly 1000 HIV-infected patients followed-up fo r greater than or equal to 12 months, while on the relevant therapy. Hypert riglyceridaemia was defined by triglyceride levels greater than or equal to 172 mg/dl, and hypercholesterolaemia by cholesterol levels greater than or equal to 200 mg/dl, All patients with triglyceridaemia >300 mg/dl and chol esterolaemia >220 mg/dl for at least 6 months, and unresponsive to a greate r than or equal to3-month diet, started bezafibrate (400 mg/day), and were prospectively followed-up at a greater than or equal to3-month interval, ev aluating both efficacy and tolerability of the hypolipidaemic treatment, pr ovided that they did not change their protease inhibitor treatment for reas ons other than metabolic abnormalities. Results: Hypertrygliceridaemia occurred in 75 patients out of 200 (37.5%), but was significantly more frequent and severe with ritonavir vs. indinavir (P < 0.001), and in subjects given indinavir vs. all remaining patients (e ither treated or not) (P < 0.001), while isolated saquinavir use was associ ated with higher tri glyceride levels than NRTI-NNRTI treatment alone, or n o antiretroviral therapy (P < 0.03). Hypercholesterolaemia was found in 27 subjects (13.5%), and a significantly higher frequency and severity was sho wn in patients treated with indinavir and ritonavir vs, saquinavir, NRTI-NN RTI, and no anti-HIV therapy (P < 0.05 to P < 0.001), No appreciable differ ence was found between patients undergoing NRTI-NNRTI and untreated control s, for all evaluated variables. Bezafibrate was administered once daily for 6-18 months to 49 patients with elevated and diet-resistant hyperlipidaemi a due to ritonavir or indinavir (27 and 22 subjects, respectively), and red uced triglyceride and cholesterol levels by 35% and 25%, respectively over 6 months, without differences between the underlying protease inhibitor reg imen. Thirty-three patients (67.3%) reached a normal triglyceridaemia after 6-9 months, and normal cholesterol levels were obtained in all subjects. B ezafibrate proved safe and well tolerated. Conclusions: Careful monitoring of the serum lipid profile is needed during antiretroviral therapy, including protease inhibitors, to identify the nee d for a diet and/or an hypolipidaemic treatment, and to prevent clinical se quelae related to long-term dyslipidaemia. Specific guidelines for the mana gement of disorders of lipid metabolism in HIV-infected patients are needed . (C) 2001 The British Infection Society.