title: 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.
authors: Department of Medicine, University of California, Los Angeles, Los Angeles, California 90035, USA. jlake@mednet.ucla.edu
authors: Jordan E
authors: JE
authors: Lake
authors: Grace A
authors: GA
authors: McComsey
authors: Todd M
authors: TM
authors: Hulgan
authors: Christine A
authors: CA
authors: Wanke
authors: Alexandra
authors: A
authors: Mangili
authors: Sharon L
authors: SL
authors: Walmsley
authors: M Sean
authors: MS
authors: Boger
authors: Ralph R
authors: RR
authors: Turner
authors: Heather E
authors: HE
authors: McCreath
authors: Judith S
authors: JS
authors: Currier
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D049628:Body Size; D002097:C-Reactive Protein / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D005260:Female; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage*; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D006984:Hypertrophy / Q000139:chemically induced; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D008137:Longitudinal Studies; D011760:Pyrrolidinones / Q000008:administration & dosage*; D011788:Quality of Life; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D019562:Viral Load / Q000187:drug effects
chemical_list: D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D011760:Pyrrolidinones; D018894:Reverse Transcriptase Inhibitors; D000068898:Raltegravir Potassium; D002097:C-Reactive Protein