DigiPrEP: A pilot trial to evaluate the feasibility, acceptability, and accuracy of a digital pill system to measure PrEP adherence in men who have sex with men who use substances.

Background Adherence to once-daily oral pre-exposure prophylaxis (PrEP) for HIV prevention can be challenging for men who have sex with men (MSM) with substance use. Digital pill systems (DPS) comprise a radiofrequency emitter integrated into a gelatin capsule containing PrEP, which transmits data to a wearable Reader following ingestion, thereby enabling direct, real-time adherence measurement. This study evaluated the feasibility, acceptability, and accuracy of a DPS to measure PrEP adherence. Methods A 90-day, single-arm, open-label, pilot demonstration trial was conducted with adult, cisgender, HIV-negative MSM on PrEP with non-alcohol substance use. Feasibility was measured via DPS engagement and timeline follow-back. Acceptability was assessed via qualitative user experience interviews. Accuracy was evaluated via DPS performance metrics, pill counts, and dried blood spots (DBS) to quantify tenofovir diphosphate (TFV-DP). Results Sixteen MSM enrolled (median age 32); fifteen completed the study. Engagement remained stable over time. Emergent nonadherence patterns included intercurrent substance use. The DPS was largely acceptable based on interviews; the predominant barrier to use was the Reader. DPS-recorded ingestions totaled 1,099, including 83.9% Reader-detected and 16.1% manually-reported. The DPS recorded 92.2% of 1,192 total expected ingestions per pill counts. Point-biserial correlation (R=0.58, 95% CI [0.21-0.80], p=0.047) and Pearson's correlation (month one: R=0.85, 95% CI [0.57-0.95], p=0.0002; month three: R=0.75, 95% CI [0.17-0.94], p=0.0197) showed strong correlations between DPS-recorded adherence and TFV-DP in DBS. Conclusion DPS are a feasible, acceptable, and accurate method of measuring PrEP adherence in MSM with substance use. Future investigations should incorporate DPS into behavioral interventions targeting nonadherence.