Assessment of HIV antiretroviral therapy adherence by measuring drug concentrations in hair among children in rural Uganda

Abstract

Current tools for measuring medication adherence have significant limitations, especially among pediatric populations. We conducted a prospective observational study to assess the use of antiretroviral (ARV) drug levels in hair for evaluating antiretroviral therapy (ART) adherence among HIV-infected children in rural Uganda. Three-day caregiver recall, 30-day visual analog scale (VAS), Medication Event Monitoring System (MEMS), and unannounced pill counts and liquid formulation weights (UPC) were collected monthly over a one-year period. Hair samples were collected quarterly and analyzed for nevirapine (NVP) levels, and plasma HIV RNA levels were collected every six months. Among children with at least one hair sample collected, we used univariable random intercept linear regression models to compare log transformed NVP concentrations with each adherence measure, and the child’s age, sex, and CD4 count percentage (CD4%). 121 children aged 2–10 years were enrolled in the study; 74 (61%) provided at least one hair sample, and the mean number of hair samples collected per child was 1.9 (standard deviation [SD] 1.0). Three-day caregiver recall, VAS, and MEMS were found to be positively associated with increasing NVP concentration in hair, although associations were not statistically significant. UPC was found to have a non-significant negative association with increasing hair NVP concentration. In conclusion, NVP drug concentrations in hair were found to have non-significant, although generally positive, associations with other adherence measures in a cohort of HIV-infected children in Uganda. Hair collection in this population proved challenging, suggesting the need for community education and buy-in with the introduction of novel methodologies.

Rates and Predictors of Non-Adherence to Antiretroviral Therapy among HIV-Positive Individuals in Kenya: Results from the Second Kenya AIDS Indicator Survey, 2012

“…Specifically, determining and addressing barriers to adherence among rural populations, adolescents and youth and persons using illicit drugs is critical in achieving the full benefits of antiretroviral therapy, nationally and among different sub-populations. Simplified approaches for monitoring ARV adherence among ART patients with particular benefit to rural settings and among young persons, including periodic measurement of ARV drug concentration in hair, may also be considered [41,42]. …”

Current concepts for PrEP adherence in the PrEP revolution

“…Both reflect longer-term windows of exposure (i.e., weeks to months versus 7 and 14 days with plasma and PBMC, respectively) and can be more easily transported for central laboratory processing than plasma or PBMC. Acceptability has generally been high, although concerns have been raised about hair collection in some populations (39, 40). Both tenofovir and emtricitabine concentrations have been evaluated; due to differences in their half-lives, the combination of both drugs can give an idea of recent versus steady-state dosing (41, 42).…”

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

“…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]. On the other hand hair sampling requires a specialized laboratory for processing and could have limited acceptability for sampling in certain patient populations[73, 74]. …”