Reversion of metabolic abnormalities after switching from HIV-1 protease inhibitors to nevirapine

Abstract

To assess the effects of switching from HIV-1 protease inhibitors (PI) to nevirapine on metabolic abnormalities in patients with fat redistribution and on CD4 T lymphocytes and plasma HIV-1 RNA. Longitudinal data analysis of 23 consecutive patients treated with two nucleoside reverse transcriptase inhibitors and at least one PI who decided to stop PI despite sustained virological supression (<200 copies/ml) because of psychological repercussions caused by body changes. PI were replaced by nevirapine in all patients. Physical examination [including measurements of body mass index (BMI) and waist:hip ratio (WHR)], fasting cholesterol, triglycerides, glucose, insulin, CD4 T lymphocytes and plasma HIV-1 RNA were performed at baseline and every 3 months. Awareness of body changes occurred after a median of 12 months (range, 6-26 months) from the commencement of PI. Seventeen patients complained of increased abdominal girth (in 15 also of peripheral fat wasting) and six of peripheral fat wasting only. Hypertriglyceridemia (≥200mg/dl) was present in 23 (100%), hypercholesterolemia (≥200mg/dl) in 18 (78%), and impaired fasting glucose (≥110mg/dl) in seven (30%) patients. Baseline CD4 T lymphocytes were 514¥106/l (range, 83-994¥106/l). HIV-1 RNA had been <200 copies/ml a median of 9 months (range, 3-14 months) prior to withdrawal of PI. Median follow-up from the replacement of PI by nevirapine was 8 months (range, 7-11 months). Six months after PI withdrawal there was a significant improvement in cholesterol (decrease of 22%; P=0.0005), triglycerides (decrease of 57%; P=0.0001), glucose (decrease of 15%; P=0.008), and fasting insulin resistance index (decrease of 45%; P=0.0001). CD4 T-lymphocyte counts remained unchanged (401¥106/l; range, 57-941¥106/l; P=0.13) and in only one patient did the viral load become detectable at a low count (546 copies/ml; P=0.32). BMI did not vary (23.30 versus 23.56 kg/m2; P=0.73), but WHR decreased significantly from 0.91 to 0.85 (P=0.048). Twenty-one patients (91%) subjectively reported a partial improvement in their body shape (particularly in peripheral fat wasting), although none admitted to have their body shaped as prior to body changes. Metabolic abnormalities associated with potent antiretroviral regimens including PI may revert at least partially, whereas the suppression achieved may be preserved at least at mid-term after replacing PI by nevirapine.