title: Urinary eicosanoid metabolites in HIV-infected women with central obesity switching to raltegravir: an analysis from the women, integrase, and fat accumulation trial.
abstract: Chronic inflammation is a hallmark of HIV infection. Eicosanoids reflect inflammation, oxidant stress, and vascular health and vary by sex and metabolic parameters. Raltegravir (RAL) is an HIV-1 integrase inhibitor that may have limited metabolic effects. We assessed urinary F2-isoprostanes (F2-IsoPs), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB2) in HIV-infected women switching to RAL-containing antiretroviral therapy (ART). Thirty-seven women (RAL = 17; PI/NNRTI = 20) with a median age of 43 years and BMI 32 kg/m(2) completed week 24. TxB2 increased in the RAL versus PI/NNRTI arm (+0.09 versus -0.02; P = 0.06). Baseline PGI-M was lower in the RAL arm (P = 0.005); no other between-arm cross-sectional differences were observed. In the PI/NNRTI arm, 24-week visceral adipose tissue change correlated with PGI-M (rho = 0.45; P = 0.04) and TxB2 (rho = 0.44; P = 0.005) changes, with a trend seen for PGE-M (rho = 0.41; P = 0.07). In an adjusted model, age ≥ 50 years (N = 8) was associated with increased PGE-M (P = 0.04). In this randomized trial, a switch to RAL did not significantly affect urinary eicosanoids over 24 weeks. In women continuing PI/NNRTI, increased visceral adipose tissue correlated with increased PGI-M and PGE-M. Older age (≥ 50) was associated with increased PGE-M. Relationships between aging, adiposity, ART, and eicosanoids during HIV-infection require further study.
authors.affiliation: Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Hulgan
authors.affiliation: Medical University of South Carolina, Charleston, SC 29403, USA.
authors.forename: M Sean
authors.initials: MS
authors.lastname: Boger
authors.affiliation: University of California, Los Angeles, CA 90035, USA.
authors.forename: Diana H
authors.initials: DH
authors.lastname: Liao
authors.affiliation: Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
authors.affiliation: Tufts University, Boston, MA 02111, USA.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Wanke
authors.affiliation: Tufts University, Boston, MA 02111, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Mangili
authors.affiliation: University of Toronto, Toronto, ON, Canada M5R 0A3.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Walmsley
authors.affiliation: University of California, Los Angeles, CA 90035, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: McCreath
authors.affiliation: Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Ginger L
authors.initials: GL
authors.lastname: Milne
authors.affiliation: Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Sanchez
authors.affiliation: University of California, Los Angeles, CA 90035, USA.
authors.forename: Judith S
authors.initials: JS
authors.lastname: Currier
authors.affiliation: University of California, Los Angeles, CA 90035, USA.
authors.forename: Jordan E
authors.initials: JE
authors.lastname: Lake
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D015777:Eicosanoids / Q000652:urine*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000652:urine*; D006801:Humans; D019426:Integrases / Q000378:metabolism*; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000652:urine*; D011760:Pyrrolidinones / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*
chemical_list: D015777:Eicosanoids; D011760:Pyrrolidinones; D018894:Reverse Transcriptase Inhibitors; D000068898:Raltegravir Potassium; D019426:Integrases