Comparison of efavirenz levels in blood and hair with pharmacy refills as measures of adherence and predictors of viral suppression among people living with HIV in Nigeria

Abstract

Background Strategies to support adherence are constrained by the lack of tools to objectively monitor medication intake in low-resource settings. Pharmacologic measures are objective, but pharmacy refill data is more accessible and cost-efficient. This study compared short-term and long-term efavirenz (EFV) drug levels with pharmacy refill adherence data (PRA) and evaluated their ability to predict viral suppression among people living with HIV in Nigeria. Methods Paired hair and dried blood spot (DBS) samples were obtained from 91 adults living with HIV receiving 600 mg EFV-based antiretroviral therapy (ART) and EFV concentrations were measured via validated methods using liquid-chromatography-mass-spectrometry. PRA was estimated from pharmacy records, based on the number of days a patient collected medication before or after the scheduled pick-up date. PRA was categorized into ≤ 74%, 75–94% and ≥ 95%, defined as poor, medium and high adherence, respectively. HIV viral loads closest to the hair sampling time (within 6 months) were also abstracted. Receiver Operating Characteristics (ROC) curve analyses compared the ability of adherence metrics to predict viral suppression. Results Based on PRA, 81% of participants had high adherence while 11% and 8% had medium and poor adherence, respectively. The median (IQR) EFV concentrations were 6.85 ng/mg (4.56–10.93) for hair and 1495.6 ng/ml (1050.7–2365.8) for DBS. Of the three measures of adherence, hair EFV concentration had the highest Area Under Curve (AUC) to predict viral suppression. Correlations between EFV concentrations in DBS and hair with PRA were positive (r = 0.12, P = 0.27 and r = 0.21, P = 0.05, respectively) but not strong. Conclusions EFV concentrations in hair were the strongest predictor of viral suppression and only weakly correlated with pharmacy refill adherence data in Nigeria. This study suggests that resource-limited settings may benefit from objective adherence metrics to monitor and support adherence.

Estimating the Effect of COVID-19 Pandemic Restrictions on Self-reported Antiretroviral Therapy Use and Late Refill Visits Among People Living With HIV in Rural South Africa

“…With a retrospective study design, the measure of self-reported missed ART doses at each refill visit was the best variable that we could utilize as a proxy for adherence in our study. Future studies should consider using objective medication adherence measures in the design stage to minimize potential measurement bias, whether that is continued use of dried blood spots 22 or alternatives such as hair samples, 23 electronic adherence monitors, 24 and ingestible sensors. 25 Limitations of this study included a small sample size resulting in limited statistical power, very specific time periods corresponding to changing COVID-19 alert levels during the first COVID-19 wave in South Africa resulting in limited generalizability, and self-reported ART adherence resulting in measurement error (internal validity) concerns.…”

“…With a retrospective study design, the measure of self-reported missed ART doses at each refill visit was the best variable that we could utilize as a proxy for adherence in our study. Future studies should consider using objective medication adherence measures in the design stage to minimize potential measurement bias, whether that is continued use of dried blood spots 22 or alternatives such as hair samples, 23 electronic adherence monitors, 24 and ingestible sensors. 25…”

Adherence determination using urine-tenofovir point-of-care testing and pharmacy refill records: A cross-sectional study

“…Sample size calculation for the study was based on proportion of 27% of non-adherence reported for pharmacy refill records from 2 African studies. [18,19] Assumptions made in the sample size calculation were, 5% precision, 5% type 1 error, and population size < 10,000. was The calculated sample size was ninety-one (91), and 100 persons were assessed for study participation eligibility. Four of those assessed were ineligible because they were not on tenofovir-based ART regimens while 2 persons declined providing consent.…”