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

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.

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.

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.

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.

Reg No. NCT01539226. Registered on February 24, 2012.