Brief Report: Ritonavir Concentrations in Hair Predict Virologic Outcomes in HIV-Infected Adolescents with Virologic Failure on Atazanavir-Based or Ritonavir-Based Second-Line Treatment

Background:Suboptimal adherence to antiretroviral therapy (ART) is responsible for most virologic failure among adolescents with HIV. Methods for objectively measuring adherence to ART are limited. This study assessed the association between ritonavir concentrations in hair and self-reported adherence and modified directly administered ART on virologic outcomes among HIV-infected adolescents who were virologically failing second-line ART in Harare, Zimbabwe.Methods:HIV-infected adolescents on atazanavir-based or ritonavir-based second-line treatment for >6 months with viral load ≥1000 copies/mL were randomized to either modified directly administered ART (mDAART) plus standard of care (intervention) or standard of care alone (control). Questionnaires were administered; viral load and hair samples were collected at baseline and after 90 days. Virological suppression was defned as <1000 copies/mL after follow-up.Results:Fifty adolescents (13-19 years) were enrolled in the study, and 42 adolescents had ritonavir concentrations measured in hair at baseline and at 90 days. Twenty-three participants (46%) were randomized to mDAART. Viral load suppression at follow-up [regression coefficient (standard error): -0.3 (0.1); 95% confidence interval (CI): -0.5 to -0.06; P = 0.01], self-reported adherence at follow-up [regression coefficient (standard error): 0.01 (0.005); 95% CI: 0.004 to 0.02; P = 0.006], and being male sex [regression coefficient (standard error): 0.3 (0.1); 95% CI: 0.08 to 0.5; P = 0.008] were associated with ritonavir concentrations in hair. The intervention, mDAART, was not associated with ritonavir concentrations [regression coefficient (standard error) 0.2 (0.1); 95% CI: -0.07 to 0.4; P = 0.2].Conclusions:Ritonavir concentrations in hair predicted virological suppression and were associated with self-reported adherence and being male in this cohort of adolescents with treatment failure to atazanavir-based or ritonavir-based second-line ART. Measuring ritonavir concentrations in hair in adolescents on protease inhibitor-based regimens could assess adherence in this vulnerable group to avert subsequent virologic failure.