The ability to assess adherence to therapy in clinical trials is essential to accurately evaluate the efficacy of HIV infection prevention methods. Four recent clinical trials have demonstrated that pre-exposure prophylaxis (PrEP) regimens may prevent HIV infection in a significant proportion of individuals [1–5]; however, two additional HIV PrEP trials showed no efficacy [6, 7]. The trial failures were due in large part to poor adherence to the prescribed antiretroviral dosing regimens . The importance of adherence in topical PrEP is underscored in the results of the CAPRISA 004 trial of a 1% tenofovir vaginal gel. The decrease in HIV infection was 54% in women with over 80% adherence to prescribed, pericoital gel use compared to 28% in women with less than 50% adherence . Self-reporting adherence has been shown to be highly inaccurate: in the Carraguard microbicide trial, participants reported 94% gel use, but a dye indicator on the applicators showed only 61% of returned applicators had been used in 43% of sex acts . Assessment of intravaginal ring (IVR) adherence is more difficult because a single IVR is often used for one month or more, and can be removed for long periods. The ASPIRE clinical trial of an IVR delivering dapivirine showed increased efficacy against HIV-1 infection in subgroups exhibiting the highest adherence; however, accurate assessment of continuous IVR use over 1 month was difficult using the metrics of amount of dapivirine recovered from used devices and plasma dapivirine concentrations at clinic visits .