Nevirapine Concentration in Hair Samples Is a Strong Predictor of Virologic Suppression in a Prospective Cohort of HIV-Infected Patients.

Sanjiv M Baxi,Wendy J Mack,Monica Gandhi,Chengshi Jin,Ruth M Greenblatt,Audrey L French,Marla J Keller,Chenglong Liu,Stephen J Gange,Peter Bacchetti,Michael H Augenbraun,J Gerardo Garcia-Lerma

doi:10.1371/journal.pone.0129100

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.

Highlights

The primary measure of treatment success for antiretroviral therapy is suppression of plasma viremia below assay threshold
The multivariate model of virologic suppression as an outcome is summarized in Table 2, where NVP concentration in hair was analyzed by quartile with n = 714 observations available for analysis
Of particular note was the finding of a significantly lower probability of viral suppression in African-American women [OR 0.09, 95% CI 0.03– 0.33, P = 0.0003] when adjusted for NVP concentration

Summary

Introduction

The primary measure of treatment success for antiretroviral therapy is suppression of plasma viremia below assay threshold. Numerous studies have demonstrated that suppression of HIV viremia predicts decreased mortality and morbidity and lowers risk of HIV transmission [1,2,3,4]. In the United States, aggregate data shows that only 81% of HIV-infected patients who receive antiretroviral therapy (ART) achieve viral suppression with suppression rates demonstrating significant variability in different populations [3]. Treatment failure is often associated with inadequate adherence, inadequate drug exposure due to biologic factors, or viral resistance to drugs in the regimen [3]. Self-report of treatment adherence is variably predictive of treatment outcomes [9,10,11,12], and adherence does not influence biologically-driven variability in ART exposure or virus-specific factors

Methods

Results

Conclusion