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.
OBJECTIVE
To assess the correlation between antiretroviral treatment and dyslipidaemia in HIV-infected patients, and the role of bezafibrate as a lipid-lowering agent.


METHODS
We retrospectively compared serum lipid levels of five groups of 40 patients, each of them treated with either saquinavir hard gel, indinavir, or ritonavir (associated with two nucleoside analogues), or dual nucleoside reverse transcriptase inhibitors (NRTI) with or without a non-nucleoside reverse transcriptase inhibitor (NNRTI), or not treated with antiretrovirals, randomly selected from nearly 1000 HIV-infected patients followed-up for >or= 12 months, while on the relevant therapy. Hypertriglyceridaemia was defined by triglyceride levels >or= 172 mg/dl, and hypercholesterolaemia by cholesterol levels >or= 200 mg/dl. All patients with triglyceridaemia > 300 mg/dl and cholesterolaemia > 220 mg/dl for at least 6 months, and unresponsive to a >or= 3-month diet, started bezafibrate (400 mg/day), and were prospectively followed-up at a <or= 3-month interval, evaluating both efficacy and tolerability of the hypolipidaemic treatment, provided that they did not change their protease inhibitor treatment for reasons 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 (either treated or not) (P<0.001), while isolated saquinavir use was associated with higher tri glyceride levels than NRTI-NNRTI treatment alone, or no antiretroviral therapy (P<0.03). Hypercholesterolaemia was found in 27 subjects (13.5%), and a significantly higher frequency and severity was shown in patients treated with indinavir and ritonavir vs. saquinavir, NRTI-NNRTI, and no anti-HIV therapy (P<0.05 to P<0.001). No appreciable difference was found between patients undergoing NRTI-NNRTI and untreated controls, for all evaluated variables. Bezafibrate was administered once daily for 6-18 months to 49 patients with elevated and diet-resistant hyperlipidaemia due to ritonavir or indinavir (27 and 22 subjects, respectively), and reduced triglyceride and cholesterol levels by 35% and 25%, respectively over 6 months, without differences between the underlying protease inhibitor regimen. Thirty-three patients (67.3%) reached a normal triglyceridaemia after 6-9 months, and normal cholesterol levels were obtained in all subjects. Bezafibrate proved safe and well tolerated.


CONCLUSIONS
Careful monitoring of the serum lipid profile is needed during antiretroviral therapy, including protease inhibitors, to identify the need for a diet and/or an hypolipidaemic treatment, and to prevent clinical sequelae related to long-term dyslipidaemia. Specific guidelines for the management of disorders of lipid metabolism in HIV-infected patients are needed.
Manfredi
R
R
Department of Clinical and Experimental Medicine, Division of Infectious Diseases, University of Bologna, S. Orsola Hospital, Bologna, Italy.
Chiodo
F
F
D001629:Bezafibrate / Q000627:therapeutic use*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000188:drug therapy; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy*; D015228:Hypertriglyceridemia / Q000139:chemically induced / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D019469:Indinavir / Q000009:adverse effects; D008055:Lipids / Q000097:blood; D012189:Retrospective Studies; D019438:Ritonavir / Q000009:adverse effects; D019258:Saquinavir / Q000009:adverse effects
D017320:HIV Protease Inhibitors; D000960:Hypolipidemic Agents; D008055:Lipids; D019469:Indinavir; D019258:Saquinavir; D019438:Ritonavir; D001629:Bezafibrate