title: Switch to raltegravir decreases soluble CD14 in virologically suppressed overweight women: the Women, Integrase and Fat Accumulation Trial.
abstract: OBJECTIVE
  Soluble CD14 (sCD14) is a monocyte activation marker associated with increased mortality in HIV infection. We assessed 48-week changes in sCD14 and other inflammatory biomarkers in virologically suppressed, HIV-infected women switching to raltegravir (RAL) from a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI).
  
  
  METHODS
  HIV-infected women with central adiposity and HIV-1 RNA < 50 HIV-1 RNA copies/mL continued their thymidine-sparing nucleoside reverse transcriptase inhibitor (NRTI) backbone and were randomized to switch to open-label RAL at week 0 (immediate) or 24 (delayed). In an exploratory analysis, inflammatory biomarkers were measured on stored fasting plasma.
  
  
  RESULTS
  Of the 37 evaluable subjects, 78% were non-White; the median age was 43 years, the median body mass index (BMI) was 32 kg/m(2) and the median CD4 count was 558 cells/μL. At baseline, biomarker values were similar between groups. After 24 weeks, median sCD14 significantly declined in subjects switching to RAL [-21% (P < 0.001) vs. PI/NNRTI -5% (P = 0.49); between-group P < 0.01]. After 48 weeks, immediate-switch subjects maintained this decline and delayed-switch subjects experienced a similar decline following the switch to RAL (-10%; within-group P < 0.01). Immediate-switch subjects also experienced an initial increase in tumour necrosis factor (TNF)-α that was neither maintained after 48 weeks nor seen in delayed-switch subjects. After adjustment for multiple testing, only declines in sCD14 remained significant.
  
  
  CONCLUSIONS
  In this randomized trial of women with central adiposity, a switch to RAL from a PI or NNRTI was associated with a statistically significant decline in sCD14. Further studies are needed to determine whether integrase inhibitors have improved monocyte activation profiles compared with PIs and/or NNRTIs, and whether measured differences between antiretroviral agents translate to demonstrable clinical benefit.
authors: Department of Medicine, University of California, Los Angeles, CA, USA.
authors: J E
authors: JE
authors: Lake
authors: G A
authors: GA
authors: McComsey
authors: T
authors: T
authors: Hulgan
authors: C A
authors: CA
authors: Wanke
authors: A
authors: A
authors: Mangili
authors: S L
authors: SL
authors: Walmsley
authors: S A
authors: SA
authors: Stramotas
authors: R
authors: R
authors: Tracy
authors: J S
authors: JS
authors: Currier
mesh_terms: D050153:Abdominal Fat; D050154:Adiposity / Q000276:immunology; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D057915:Drug Substitution; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008875:Middle Aged; D050177:Overweight / Q000378:metabolism*; D011760:Pyrrolidinones / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D019428:HIV Integrase Inhibitors; D018950:Lipopolysaccharide Receptors; D011760:Pyrrolidinones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000068898:Raltegravir Potassium
keywords: inflammation; monocyte activation; raltegravir; sCD14; women