title: Atazanavir concentration in hair is the strongest predictor of outcomes on antiretroviral therapy.
abstract: BACKGROUND
  Adequate exposure to antiretrovirals is important to maintain durable responses, but methods to assess exposure (eg, querying adherence and single plasma drug level measurements) are limited. Hair concentrations of antiretrovirals can integrate adherence and pharmacokinetics into a single assay.
  
  
  METHODS
  Small hair samples were collected from participants in the Women's Interagency HIV Study (WIHS), a large cohort of human immunodeficiency virus (HIV)-infected (and at-risk noninfected) women. From 2003 through 2008, we analyzed atazanavir hair concentrations longitudinally for women reporting receipt of atazanavir-based therapy. Multivariate random effects logistic regression models for repeated measures were used to estimate the association of hair drug levels with the primary outcome of virologic suppression (HIV RNA level, <80 copies/mL).
  
  
  RESULTS
  424 WIHS participants (51% African-American, 31% Hispanic) contributed 1443 person-visits to the analysis. After adjusting for age, race, treatment experience, pretreatment viral load, CD4 count and AIDS status, and self-reported adherence, hair levels were the strongest predictor of suppression. Categorized hair antiretroviral levels revealed a monotonic relationship to suppression; women with atazanavir levels in the highest quintile had odds ratios (ORs) of 59.8 (95% confidence ratio, 29.0-123.2) for virologic suppression. Hair atazanavir concentrations were even more strongly associated with resuppression of viral loads in subgroups in which there had been previous lapses in adherence (OR, 210.2 [95% CI, 46.0-961.1]), low hair levels (OR, 132.8 [95% CI, 26.5-666.0]), or detectable viremia (OR, 400.7 [95% CI, 52.3-3069.7]).
  
  
  CONCLUSIONS
  Antiretroviral hair levels surpassed any other predictor of virologic outcomes to HIV treatment in a large cohort. Low antiretroviral exposure in hair may trigger interventions prior to failure or herald virologic failure in settings where measurement of viral loads is unavailable. Monitoring hair antiretroviral concentrations may be useful for prolonging regimen durability.
authors.affiliation: Departments of Medicine, University of California, San Francisco, 94122, USA. monica.gandhi@ucsf.edu
authors.forename: Monica
authors.initials: M
authors.lastname: Gandhi
authors.forename: Niloufar
authors.initials: N
authors.lastname: Ameli
authors.forename: Peter
authors.initials: P
authors.lastname: Bacchetti
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gange
authors.forename: Howard
authors.initials: H
authors.lastname: Minkoff
authors.forename: Mary
authors.initials: M
authors.lastname: Young
authors.forename: Joel
authors.initials: J
authors.lastname: Milam
authors.forename: Mardge H
authors.initials: MH
authors.lastname: Cohen
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Sharp
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Greenblatt
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006197:Hair / Q000737:chemistry*; D006801:Humans; D008137:Longitudinal Studies; D055118:Medication Adherence; D008875:Middle Aged; D015233:Models, Statistical; D009842:Oligopeptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate