Adherence monitoring in HIV prevention trials has traditionally been limited to participant self-report or tracking of study materials (pill count or return of used gel applicators), approaches that have led to inaccurate assessment of true product use [8–10]. The ASPIRE dapivirine IVR trial incorporated an objective measure of adherence to IVR use in a large scale study in sub-Saharan Africa [30, 31]. Returned IVRs were tested for residual dapivirine levels to determine the amount of drug released. The distribution of residual dapivirine values was bimodal with one peak at 24–25 mg residual DPV indicating IVRs were unused, and a second peak at 20–21 mg indicating IVRs were used for 28 days. Using a length-adjusted analysis of the residual DPV data, seroconverting subjects were binned into four adherence groups based on the clinic visit with the lowest adherence for the three visits prior to HIV detection. A strong correlation of protection with adherence group was observed (% risk reduction, incidence per 100 person-years): no use (11%, 4.9), bottom third (29%, 3.1), middle third (58%, 1.9), top third (92%, 0.4). The placebo group exhibited an incidence of 4.7 per 100 person-years. Plasma levels of dapivirine was also measured quarterly as an additional measure of IVR use; however, insertion of the ring for 8 hours or more before a clinic visit resulted in identical plasma levels to 28 days of continuous use. Although the residual dapivirine levels only provided a snapshot of total IVR use over one month and no temporal use data, the ASPIRE data indicate that even imperfect and incomplete objective adherence data can lend valuable insight into patterns of adherence and the relationship between adherence and product efficacy in a clinical setting. The IVR use pattern obtained from the adherence module developed here would allow a much more detailed analysis than was conducted in ASPIRE, including specific time periods of IVR use, total drug dose during use period, self-report of IVR use and sexual activity, and HIV infection status to extract the key pharmacokinetic-pharmacodynamic relationships that result in HIV prevention efficacy.