title: Nanoflow-Nanospray Mass Spectrometry Metabolomics Reveals Disruption of the Urinary Metabolite Profiles of HIV-Positive Patients on Combination Antiretroviral Therapy.
abstract: BACKGROUND
  The use of combination antiretroviral therapy (cART) has substantially improved the outlook for patients with HIV infection. However, lifelong exposure to cART is also associated with adverse metabolic changes and an enhanced risk of renal, hepatic, and cardiovascular dysfunction. This study investigated disruptions of the urinary metabolome of cART-exposed patients, thereby furthering our understanding of some of the side effects of pharmaceutical intervention.
  
  
  METHODS
  HIV-positive patients were recruited from an HIV clinic and divided into cART-naive and cART-exposed groups. HIV-negative patients were recruited from a sexual health clinic. All 89 subjects were white males. Targeted biochemistry analyses were performed on plasma samples. Urine samples were collected after an overnight fast and analyzed with a highly sensitive untargeted metabolomic method using nanoflow/nanospray liquid chromatography-time-of-flight mass spectrometry. Data sets were analyzed using projection modeling to detect metabolite markers of cART exposure.
  
  
  RESULTS
  Metabolites or parent compounds of all cART drugs were detected in urine extracts of all but one of the cART-exposed patients confirming adherence to the pharmaceutical regimen. Analysis of urine samples from patients on cART revealed significant reductions in selected bile acids, lipid, nucleoside, and androgen metabolites. However, plasma concentrations of free or conjugated testosterone remained unchanged indicating possible disruption of androgen transport or excretion in urine of patients on cART.
  
  
  CONCLUSIONS
  Discovery-based metabolomics reveals the potential to identify novel markers of cART intervention and metabolite disruption in HIV-positive patients, which may enable investigation of the efficacy, compliance, and side effects of these pharmaceutical mixtures to be investigated.
authors.affiliation: *School of Life Sciences, University of Sussex, Brighton, United Kingdom; †Brighton and Sussex Medical School, Brighton, United Kingdom; ‡Brighton and Sussex University Hospitals NHS Trust, Brighton, United Kingdom; and §The Royal Melbourne Hospital, The University of Melbourne, Victoria, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Chetwynd
authors.forename: Amanda
authors.initials: A
authors.lastname: Samarawickrama
authors.forename: Jaime H
authors.initials: JH
authors.lastname: Vera
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Bremner
authors.forename: Alaa
authors.initials: A
authors.lastname: Abdul-Sada
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Gilleece
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Holt
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Hill
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D016482:Urinalysis; D014556:Urine / Q000737:chemistry*; D044465:White People; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents