Divergent adherence estimates with pharmacokinetic and behavioural measures in the MTN-003 (VOICE) study
Van Der Straten, A., Brown, ER., Marrazzo, JM., Chirenje, MZ., Liu, K., Gomez, K., Marzinke, MA., Piper, JM., & Hendrix, CW. (2016). Divergent adherence estimates with pharmacokinetic and behavioural measures in the MTN-003 (VOICE) study. Journal of the International AIDS Society, 19(1), e20642. https://doi.org/10.7448/ias.19.1.20642
INTRODUCTION: In the Microbicide Trial Network MTN-003 (VOICE) study, a Phase IIB pre-exposure prophylaxis trial of daily oral or vaginal tenofovir (TFV), product adherence was poor based on pharmacokinetic (PK) drug detection in a random subsample. Here, we sought to compare behavioural and PK measures of adherence and examined correlates of adherence misreporting.
METHODS: We included participants with PK and behavioural data from VOICE random subsample. Behavioural assessments included face-to-face interviews (FTFI), audio computer-assisted self-interviewing (ACASI) and pharmacy-returned product counts (PC). TFV concentrations < 0.31 ng/mL in plasma (oral group) and < 8.5 ng/swab in vaginal group were defined as "PK non-adherent." Logistic regression models were fit to calculate the combined predictive ability of the behavioural measures as summarized by area under the curve (AUC). Baseline characteristics associated with over-reporting daily product use relative to PK measures was assessed using a Generalized Linear Mixed Model.
RESULTS: In this random adherence cohort of VOICE participants assigned to active products, (N = 472), PK non-adherence was 69% in the oral group (N = 314) and 65% in the vaginal group (N = 158). Behaviourally, ≤ 10% of the cohort reported low/none use with any behavioural measure and accuracy was low (≤ 43%). None of the regression models had an AUC > 0.65 for any single or combined behavioural measures. Significant (p < 0.05) correlates of over-reporting included being very worried about getting HIV and being unmarried for the oral group; whereas for the vaginal group, being somewhat worried about HIV was associated with lower risk of over-reporting.
CONCLUSIONS: PK measures indicated similarly low adherence for the oral and vaginal groups. No behavioural measure accurately predicted PK non-adherence. Accurate real-time measures to monitor product adherence are urgently needed.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00705679.