title: Hair concentrations of antiretrovirals predict viral suppression in HIV-infected pregnant and breastfeeding Ugandan women.
abstract: OBJECTIVE
  Hair concentrations are a noninvasive measure of cumulative antiretroviral exposure and the strongest predictor of viral suppression in large cohorts of nonpregnant patients. We examined hair concentrations of antiretrovirals in relation to virologic outcomes in pregnant and breastfeeding women for the first time.
  
  
  METHODS
  The Prevention of Malaria and HIV Disease in Tororo trial (NCT00993031) enrolled HIV-infected pregnant Ugandan women at 12-28 weeks gestation who were randomized to lopinavir or efavirenz-based antiretroviral therapy (ART). Small hair samples were collected at 30-34 weeks gestation and 10-25 weeks postpartum. Efavirenz and lopinavir hair concentrations were measured via liquid chromatography/tandem mass spectrometry. Multivariate logistic regression models examined predictors of viral suppression (HIV-1 RNA ≤400 copies/ml) at delivery and 24 weeks postpartum.
  
  
  RESULTS
  Among 325 women, median CD4 cell count was 366 cells/μl (interquartile range 270-488) at ART initiation. Mean self-reported 3-day adherence was greater than 97% in each arm. Viral suppression was achieved by 98.0% (efavirenz) and 87.4% (lopinavir) at delivery. At 24 weeks postpartum, 92.5% (efavirenz) and 90.6% (lopinavir) achieved viral suppression; 88% of women were breastfeeding. In multivariate models including self-reported adherence and pretreatment HIV-1 RNA, antiretroviral hair concentrations were the strongest predictor of viral suppression at delivery [efavirenz: adjusted odds ratio (aOR) 1.86 per doubling in concentration, 95% confidence interval (CI) 1.14-3.1, P = 0.013; lopinavir: aOR 1.90, 95% CI 1.33-2.7, P = 0.0004] and 24 weeks postpartum (efavirenz: aOR 1.81, 95% CI 1.22-2.7, P = 0.003; lopinavir: aOR 1.53, 95% CI 1.05-2.2, P = 0.026).
  
  
  CONCLUSIONS
  Antiretroviral hair concentrations represent an innovative tool that strongly predicts viral suppression among HIV-infected childbearing women during the critical periods of delivery and breastfeeding.
authors.affiliation: aHIV/AIDS Division, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, USA bMakerere University-University of California, San Francisco Research Collaboration, Kampala, Uganda cMedical Research Council Unit, The Gambia dDepartment of Obstetrics, Gynecology and Reproductive Sciences eDepartment of Epidemiology and Biostatistics fHair Analysis Laboratory gCenter for AIDS Prevention Studies hDepartment of Pediatrics, University of California, San Francisco, San Francisco, California, USA iDepartment of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Koss
authors.forename: Paul
authors.initials: P
authors.lastname: Natureeba
authors.forename: Julia
authors.initials: J
authors.lastname: Mwesigwa
authors.forename: Deborah
authors.initials: D
authors.lastname: Cohan
authors.forename: Bridget
authors.initials: B
authors.lastname: Nzarubara
authors.forename: Peter
authors.initials: P
authors.lastname: Bacchetti
authors.forename: Howard
authors.initials: H
authors.lastname: Horng
authors.forename: Tamara D
authors.initials: TD
authors.lastname: Clark
authors.forename: Albert
authors.initials: A
authors.lastname: Plenty
authors.forename: Theodore D
authors.initials: TD
authors.lastname: Ruel
authors.forename: Jane
authors.initials: J
authors.lastname: Achan
authors.forename: Edwin D
authors.initials: ED
authors.lastname: Charlebois
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.forename: Diane V
authors.initials: DV
authors.lastname: Havlir
authors.forename: Monica
authors.initials: M
authors.lastname: Gandhi
mesh_terms: D000328:Adult; D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000032:analysis*; D048588:Benzoxazines / Q000008:administration & dosage / Q000032:analysis; D001942:Breast Feeding; D002853:Chromatography, Liquid; D015331:Cohort Studies; D003521:Cyclopropanes; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D006197:Hair / Q000737:chemistry*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D061466:Lopinavir / Q000008:administration & dosage / Q000032:analysis; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome; D014454:Uganda; D019562:Viral Load
chemical_list: D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D061466:Lopinavir; C098320:efavirenz