Background:  Switching  to a PI-sparing regimen is a common therapeutic strategy for patients with metabolic and lipodystrophic changes.

Methods:  NEFA was an open-label randomized study comparing 3 different PI-sparing regimens (ABC, EFV, and NVP) in HIV⁺ individuals who had been previously exposed to a HAART PI-containing regimens. A sub-study in 92 patients was conducted to evaluate the switching effect on metabolic and body composition parameters. Herein we present metabolic outcomes in 69 patients who maintained the initially allocated treatment for 24 months (ABC:  n = 22; EFV: n = 21; NVP:  n = 26). Fasting serum total cholesterol, low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), triglycerides, glucose, and insulin were determined. Insulin resistance  by the homeostasis model assessment and total cholesterol:HDLc ratio were also calculated.

Results:  In an overall analysis, insulin, insulin resistance, total cholesterol, LDLc, HDLc, and total cholesterol:HDLc ratio improved (baseline vs 24-month data). The 2 NNRTI showed similar metabolic benefits after 2 years of therapy. In both treatments, Total cholesterol levels did not change (NVP:  +2%, EFV:  -6%), LDLc levels tended to diminish (NVP:  -17%, EFV:  -10%), and HDLc levels significantly increased, especially in NVP patients (NVP:  +50%, EFV:  +12%). On the other hand, ABC treatment led to a significant decrease in total cholesterol (-13%) and LDLc (-15%) levels. The total cholesterol:HDLc decrease was more pronounced in the NNRTI groups (NVP:  +16%, EFV:  +15%, ABC: +5%) and triglyceride levels remained unvaried in all 3 treatment arms. At the beginning of the study, 40  patients had lipodystrophy (LD⁺). At baseline, LD⁺ patients had higher insulin and triglyceride levels. Although comparable metabolic improvements occurred in LD⁺ vs LD-free, after 24 months LD-free patients presented a significantly better lipid profile in terms of triglycerides (2.4 vs 4.8 mmol/L), HDLc (1.6 vs 1.1 mmol/L) and total cholesterol:HDLc (4.1 vs 5.2).

Conclusions:  Overall, switching to PI-sparing regimens led to a marked metabolic improvement after 24 months of follow-up. Some differences in metabolic changes were found among the 3 regimens. LD⁺ patients remained with a worse lipid profile than LD-free patients.

Keywords: Simplification; metabolic alterations; nevirapine, abacavir, efavirenz