Background:  A wide range of abnormalities of lipid metabolism has been recently described in HIV-infected patients receiving a protease inhibitor (PI)-based HAART, including hypertriglyceridemia and hypercholesteroaemia. This randomized, open-label clinical trial was conducted to assess the efficacy on hyperlipiaemia of a switching therapy from PI to non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine or efavirenz versus a hypolipidemic treatment (with pravastatin or bezafibrate) added to current, unchanged antiretroviral combination.

Methods:  Plasma lipid levels of adult HIV-infected p who referred to our tertiary care centre and were on PI-based antiretroviral therapy since at least 12 months have been evaluated. All patients were established with stable immunovirologic features (HIV viral load < 50 copies/mL and CD4 lymphocyte count > 350 cells/mL for at least 6 months), naïve to all NNRTI, and with diet-resistant mixed hyperlipidemia of at least 6 months’ duration, were randomized to replace PI with nevirapine (arm A) or efavirenz (arm B), or to receive pravastatin (arm C) or bezafibrate (arm D) with unchanged HAART regimen, and were followed-up for 12 months. Patients with prior history of suboptimal single or dual nucleoside analog therapy were excluded from the study.

Results:  We enrolled 142 patients, while 12 patients were excluded from final evaluation due to early or late drop-out. With regard to the 130 evaluable patients, 29 were randomized to arm A, 34 to arm B, 36 to arm C, and 31 to arm D. At the end of the 12-month follow-up, a reduction of 41.2%, 46.6%, 25.2%, and 9.4% in mean triglyceridaemia versus respective baseline values was reported in groups C, D, A, and B, respectively, with statistically significant difference between arms C–D and A–B (p < 0.01). At the same time, a decrease of 45.8%, 37.6%, 27.1%, and 10.2% in mean total cholesterolemia was observed in groups C, D, A, and B, respectively, with statistically significant difference between arms C–D and A–B (p < 0.01). Viro-immunologic efficacy and tolerability profile were comparable in all considered arms.

Conclusions:  Pravastatin and bezafibrate proved significantly more effective in the management of HAART-related hyperlipidemia than the switching therapy from PI to nevirapine or efavirenz, in association with maintained antiviral activity and favorable tolerability profile. Nevirapine revealed a significantly higher efficacy than efavirenz in reducing both plasma triglyceride and total cholesterol levels.

Keywords: Dyslipidemia; Switch to NNRTI; Hypolidemic treatment