Incremental value of non-pharmacokinetic adherence measures for dapivirine vaginal ring use in resource limited setting

Le résumé fourni par la source

BACKGROUND: Measuring product use adherence remains a challenge in HIV prevention trials and routine care setting. We determined agreement among and between non-pharmacokinetic (non-PK) and pharmacokinetic (PK) adherence measures, and also assessed the incremental value of each measure among women using the dapivirine vaginal ring (DVR) in the Ring trial in southwestern Uganda. METHODS: Between 2013 and 2016, the International Partnership for Microbicides conducted the Ring trial in which women were randomised to dapivirine or placebo vaginal ring in a ratio of 2:1. A total of 197 women were randomised. Four adherence measures were used, including PK: (i) testing of the dapivirine residual levels in used rings and (ii) plasma drug concentrations; non-PK: (iii) self-reported and (iv) ring colour change, all measured every 4 weeks for 2 years. We defined product use adherence as having the expected dapivirine residual levels (≤ 23.5 mg of 25 mg) or plasma concentration (≥ 95 pg/mL) or having used the ring as instructed at ≥ 80% of the visits completed. We used dapivirine residual levels as a gold standard and measured agreement and incremental value of other measures in predicting residual adherence using Cohen's kappa statistic, a discriminant C-statistic and Receiver Operating Characteristic (ROC) curve, stratified by age < 25 or ≥ 25 years. RESULTS: Of the 197 women randomised, 66% were aged ≥ 25 years and in both age groups, > 80% completed 2 years of follow-up. In women aged < 25 years, percent agreement between non-PK measures and that between non-PK and PK measures was moderate 57.8% to 66.7%. While that between PK measures was high 86.7%. In the women aged ≥ 25 years, agreements between combinations of measures were 80.5% to 86.2%. The incremental value of non-PK measures was poor in women aged < 25 years, AROC = 0.62, and good in those age 25 + years, area under receiver operating curve (AROC) = 0.77. CONCLUSION: Combining non-PK measures to measure dapivirine residual level adherence in women aged ≥ 25 years could be useful in DVR use, in the context of resource-scarce settings. However, this is of limited value in young women aged < 25 years. TRIAL REGISTRATION: Reg No. NCT01539226. Registered on February 24, 2012.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.