title: Nevirapine Concentration in Hair Samples Is a Strong Predictor of Virologic Suppression in a Prospective Cohort of HIV-Infected Patients.
abstract: Effective antiretroviral (ARV) therapy depends on adequate drug exposure, yet methods to assess ARV exposure are limited. Concentrations of ARV in hair are the product of steady-state pharmacokinetics factors and longitudinal adherence. We investigated nevirapine (NVP) concentrations in hair as a predictor of treatment response in women receiving ARVs. In participants of the Women's Interagency HIV Study, who reported NVP use for >1 month from 2003-2008, NVP concentrations in hair were measured via liquid-chromatography-tandem mass-spectrometry. The outcome was virologic suppression (plasma HIV RNA below assay threshold) at the time of hair sampling and the primary predictor was nevirapine concentration categorized into quartiles. We controlled for age, race/ethnicity, pre-treatment HIV RNA, CD4 cell count, and self-reported adherence over the 6-month visit interval (categorized ≤ 74%, 75%-94% or ≥ 95%). We also assessed the relation of NVP concentration with changes in hepatic transaminase levels via multivariate random intercept logistic regression and linear regression analyses. 271 women contributed 1089 person-visits to the analysis (median 3 of semi-annual visits). Viral suppression was least frequent in concentration quartile 1 (86/178 (48.3%)) and increased in higher quartiles (to 158/204 (77.5%) for quartile 4). The odds of viral suppression in the highest concentration quartile were 9.17 times (95% CI 3.2-26, P < 0.0001) those in the lowest. African-American race was associated with lower rates of virologic suppression independent of NVP hair concentration. NVP concentration was not significantly associated with patterns of serum transaminases. Concentration of NVP in hair was a strong independent predictor of virologic suppression in women taking NVP, stronger than self-reported adherence, but did not appear to be strongly predictive of hepatotoxicity.
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America; School of Public Health, Division of Epidemiology, University of California, Berkeley, California, United States of America.
authors.forename: Sanjiv M
authors.initials: SM
authors.lastname: Baxi
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America; Department of Clinical Pharmacy, University of California San Francisco, San Francisco, California, United States of America; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Greenblatt
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Bacchetti
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Chengshi
authors.initials: C
authors.lastname: Jin
authors.affiliation: CORE Center and Division of Infectious Diseases, John H. Stroger Jr. Hospital of Cook County, Chicago, Illinois, United States of America.
authors.forename: Audrey L
authors.initials: AL
authors.lastname: French
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America; Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Marla J
authors.initials: MJ
authors.lastname: Keller
authors.affiliation: Division of Infectious Diseases, State University of New York, Downstate Medical Center, Brooklyn, New York, United States of America.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Augenbraun
authors.affiliation: Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gange
authors.affiliation: Department of Medicine, Georgetown University Medical Center, Washington DC, United States of America.
authors.forename: Chenglong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Mack
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Monica
authors.initials: M
authors.lastname: Gandhi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D006197:Hair / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016017:Odds Ratio; D011446:Prospective Studies; D014018:Tissue Distribution; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine