A Randomized Trial of Raltegravir Replacement for Protease Inhibitor or Non-Nucleoside Reverse Transcriptase Inhibitor in HIV-Infected Women with Lipohypertrophy

Abstract

Lipohypertrophy in HIV-infected patients is associated with metabolic abnormalities. Raltegravir (RAL) is not known to induce fat changes or severe metabolic perturbations. HIV-infected women with central adiposity and HIV-1 RNA less than 50 copies per milliliter on non-nucleoside reverse transcriptase inhibitor (NNRTI)-or protease inhibitor (PI)-based antiretroviral therapy (ART) continued their nucleoside reverse transcriptase inhibitor (NRTI) backbone and were randomized to switch to open label RAL immediately or after 24 weeks. The primary end point was 24-week between-group change in computed tomography (CT)-quantified visceral adipose tissue (AT) volume. Fasting lipids, glucose, C-reactive protein (CRP), anthropometric measurements, and patient-reported quality of life assessments were also measured. Thirty-six subjects provided 80% power to detect a 10% between-group difference in visceral AT over 24 weeks. Thirty-seven of 39 enrolled subjects completed week 24. At entry, subjects were 75% black or Hispanic, and on 62% PI-based and 38% NNRTI-based regimens. The median age was 43 years, CD4 count 558 cells per microliter, and body mass index (BMI) 32 kg/m 2 . After 24 weeks, no statistically significant changes in visceral or subcutaneous AT, anthropometrics, BMI, glucose, or CRP were observed. In subjects receiving RAL, significant improvements in total and LDL cholesterol ( p = 0.04), self-reported belly size ( p = 0.02) and composite body size ( p = 0.02) were observed. Body size changes correlated well with percent visceral AT change. No RAL-related adverse events occurred. Compared to continued PI or NNRTI, switch to RAL was associated with statistically significant 24-week improvements in total and LDL cholesterol but not AT volumes. Additional insights into AT and metabolic changes in women on RAL will be provided by 48-week follow-up of the immediate-switch arm.

Effects of Switching From Efavirenz to Raltegravir on Endothelial Function, Bone Mineral Metabolism, Inflammation, and Renal Function

“…Total cholesterol levels improved in the Switch Group, which corroborates findings from previous studies assessing switches from protease inhibitors 15, 19, 20 or EFV 20 to RAL. Similar findings in ART-naïve studies comparing RAL to EFV showed less effects of RAL on lipid profiles.…”

“…20 We also explored potential changes in sCD14 and sCD163 as markers of monocyte activation with switch to RAL. Greater sCD14 levels have been linked to an increased risk of death 25 while higher sCD163 levels have been associated with worsening inflammatory atherosclerotic disease in those with HIV infection.…”

Association News

“…Lipodystrophy causes a redistribution of fat and unusual changes in body habitus such that there is an increase in abdominal girth; the appearance of ''fat padding'' or ''buffalo hump'' on the back of the neck; enlarged breasts in both men and women; and thinning and wasting of subcutaneous fat tissue of the arms, face, and buttocks. 1,2 The reason for the development of lipodystrophy in HIV-infected people is most likely multifactorial and related to immune depletion and immune recovery, antiretroviral medications, dysregulation of fatty acid metabolism, hormonal influences, and individual genetic predispositions. NonYHIV-related factors include female sex, older age, diet, and obesity.…”

Urine Eicosanoids in the Metabolic Abnormalities, Telmisartan, and HIV Infection (MATH) Trial

“…[29] Telmisartan is an angiotensin receptor blocker (ARB) and partial PPAR-γ agonist with potential metabolic and anti-inflammatory benefits,[30,31] including improvements in visceral adipose tissue (VAT) volume, fasting glucose and lipid profiles, and markers of oxidative stress and vascular inflammation in primarily HIV-uninfected populations. [32–35] The Metabolic Abnormalities, Telmisartan, and HIV Infection (MATH) trial was a pilot study designed to assess the effects of 24 weeks of telmisartan on visceral adiposity and metabolic parameters in HIV-infected participants with central adiposity on suppressive ART.…”