Using Lopinavir Concentrations in Hair Samples to Assess Treatment Outcomes on Second-Line Regimens Among Asian Children

Abstract

We conducted a prospective monitoring study to determine whether antiretroviral (ARV) levels in hair of Asian children on second-line protease inhibitor-based ARV therapy (ART) are associated with virologic failure (VF), compared to plasma drug levels and self-reported adherence. HIV-infected Asian children on second-line ART regimens were enrolled into a longitudinal cohort. Traditional adherence measures, plasma, and hair samples were collected 24 weeks after study enrollment. Hair ARV levels were determined via liquid chromatography/ tandem mass spectrometry. Among 149 children on lopinavir/ritonavir-based regimens, 47% were female; the median [interquartile range (IQR)] age was 10.3 (7.9-13.3) years. The median CD4% was 26% (IQR 21.7-32.1%) and the median CD4 cell count 754 (IQR 596-1,013) cells/mm 3 . The median duration of lopinavirbased ART prior to week 24 of the study was 2.9 (IQR 1.6-4.2) years. Adherence was >95% in 91% (135/148) by visual analogue scale and 89% (129/145) by pill count. The median lopinavir hair concentrations were 5.43 (IQR 3.21-9.01) ng/mg in children with HIV RNA >1,000 copies/ml and 9.96 (IQR 6.51-12.31) ng/mg in children with HIV RNA <1,000 copies/ml ( p = 0.003). Plasma trough and lopinavir hair concentrations were not statistically significantly correlated (Pearson's correlation coefficient 0.20; p = 0.13). Increasing lopinavir hair concentrations in quartiles were strongly associated with virologic success (odds ratios ‡4.0, overall p = 0.02), while self-reported adherence, pill count, and plasma lopinavir levels were not. Based on this first report of hair ARV concentrations and virologic outcomes in children, ARV hair concentrations, representing longer-term adherence, may be useful to identify children at risk for VF.

Adherence Measurements in HIV: New Advancements in Pharmacologic Methods and Real-Time Monitoring

“…However, a strong body of literature has emerged on the use of hair as a measure of cumulative exposure to a wide variety of therapies[66, 67] and endogenous hormones[68, 69]. Hair collection offers the advantage that it can be obtained in various clinical and non-clinical settings[70, 71], does not require special training or equipment, and can be shipped without biohazard concerns and without the need of a cold chain. It can also be evaluated to determine adherence at different time points in the preceding weeks/months, as the drug concentrations in the proximal vs. the distal segments of the hair strand reflect the effect of time on drug exposure[72].…”

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

“…The utility of hair concentrations as a metric of adherence and exposure in HIV-infected adults has been explored, 5,8 but the study of this measure in adolescents is more limited 7 . This study sought to assess the relationship between atazanavir hair concentration and virological outcomes, as well as self-reported adherence, among HIV-infected adolescents with virological failure on atazanavir/ritonavir-based 2 nd -line treatment in Harare, Zimbabwe.…”

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

“…Hair concentrations of ARVs are a non-invasive measure that reflect cumulative systemic drug exposure and predict viral suppression in adults better than self-reported adherence, [3, 4] single plasma ARV levels, [5] and host or viral characteristics, such as immune status and pre-treatment viral loads [4, 6, 7] . Hair sampling may be a particularly desirable approach for monitoring adherence/exposure in pediatric populations, since hair collection is painless and avoids phlebotomy [8] .…”

“…Hair sampling may be a particularly desirable approach for monitoring adherence/exposure in pediatric populations, since hair collection is painless and avoids phlebotomy [8] . We previously demonstrated an association of ARV hair concentrations with virologic responses among HIV-infected children on second-line ART in Southeast Asia [5] . The prior analysis was cross-sectional and did not allow for the predictive utility of hair concentrations on viremia to be examined.…”