Defining a Cutoff for Atazanavir in Hair Samples Associated With Virological Failure Among Adolescents Failing Second-Line Antiretroviral Treatment

Abstract

Background Adequate antiretroviral exposure is crucial for virological suppression. We assessed the relationship between atazanavir hair levels with self-reported adherence, virological outcomes, and the effect of a home-based adherence intervention in HIV-infected adolescents failing 2nd-line antiretroviral treatment in Zimbabwe. Methods HIV-infected adolescents on atazanavir/ritonavir-based 2nd-line treatment for ≥6 months with viral load (VL) >1,000 copies/ml were randomised to either standard care (control) or standard care plus modified directly administered antiretroviral therapy (mDAART) (intervention). Questionnaires were administered; VL and hair samples were collected at baseline and after 90 days in each group. Viral suppression was defined as <1,000 copies/ml after follow-up. Results Fifty adolescents (10–18 years) were enrolled; 23(46%) were randomized to intervention and 27(54%) to control. Atazanavir hair concentration <2.35ng/mg (lower inter-quartile range for those with virological suppression) defined a cut-off below which most participants experienced virological failure. Male sex (p=0.03), virological suppression at follow-up (p=0.013), greater reduction in VL (p=0.006) and change in average self-reported adherence over the previous month (p=0.031) were associated with adequate (>2.35ng/mg) hair concentrations. Participants with virological failure were more likely to have sub-optimal atazanavir hair concentrations (RR=7.2, 95% CI=1–51, p=0.049). There were no differences in atazanavir hair concentration between the arms after follow-up. Conclusion A threshold of atazanavir concentrations in hair (2.35ng/mg), above which virological suppression was likely, was defined for adolescents failing 2nd line atazanavir/ritonavir-based ART in Zimbabwe. Male sex and better self-reported adherence were associated with adequate atazanavir hair concentrations. Antiretroviral hair concentrations may serve as a useful clinical tool among adolescents.

Brief Report: Lopinavir Hair Concentrations Are the Strongest Predictor of Viremia in HIV-Infected Asian Children and Adolescents on Second-Line Antiretroviral Therapy

“…Our results add to the previously limited data on using non-invasive objective measures of ART adherence and drug exposure in pediatric populations. These findings – and a recently-published study showing a similar finding for atazanavir (ATV) hair levels among adolescents on ATV-based 2 nd line-ART [15] - suggest that hair concentrations of ARVs can inform clinical decision-making around the management of viremia among HIV-infected children and adolescents by identifying those at risk for treatment failure due to chronically low drug levels.…”

Development and validation of an assay to analyze atazanavir in human hair via liquid chromatography/tandem mass spectrometry

“…Studies have shown strong relationships between ATV levels in hair and virologic outcomes among HIV‐infected patients on ATV‐based therapy . The most recently published study was conducted among adolescents in Zimbabwe failing second‐line ART and our laboratory analyzed the ATV concentrations in hair samples collected at baseline and 3 months.…”

“…The pigmentation in hair is from melanin, which is associated with the drug binding rate in hair only if the drug is primarily basic (although not acidic) . Despite these limitations, our group (the UCSF Hair Analytical Laboratory) has found that hair ARV measurements are stronger predictors of HIV outcomes than self‐reported adherence, or single plasma ARV concentrations, in HIV treatment, and are useful for adherence and toxicity monitoring in the context of pre‐exposure prophylaxis (PrEP) . Moreover, we have not found significant differences in median and range hair concentrations of ARVs by race/ethnicity.…”

“…Studies have shown strong relationships between ATV levels in hair and virologic outcomes among HIV‐infected patients on ATV‐based therapy . The most recently published study was conducted among adolescents in Zimbabwe failing second‐line ART and our laboratory analyzed the ATV concentrations in hair samples collected at baseline and 3 months. The median ATV hair concentrations among those experiencing virologic failure (defined by HIV RNA >400 copies/mL) was 0.99 ng/mg and the median ATV hair levels among those with virologic success was 3.33 ng/mg (p = 0.0042).…”

“…One way to objectively monitor adherence is to analyze antiretroviral (ARV) drug concentrations in different biomatrices. Our group has developed expertise in the measurement of ARV levels in hair to assess adherence and its exposure in the context of both HIV prevention and treatment …”