Development of Ingestible Biosensors to Enhance PrEP Adherence in Substance Users (PrEPSteps) (PrEPSteps)

This study will deploy a novel, personalized, smartphone-based intervention (PrEPSteps) that responds to real-time PrEP adherence and nonadherence detected through the use of a digital pill. The PrEPSteps intervention will be developed and refined through a series of focus groups. Participants will be screened at the Screening Visit, and, if eligible, will then begin using the digital pill system at Study Visit 1 for 2 weeks. At Study Visit 2, participants will undergo randomization to using either PrEPSteps + the digital pill, or the digital pill alone to measure PrEP adherence, for 90 days. Participants will then complete 3 monthly study visits (Study Visits 3-5) where the investigators will assess digital pill adherence, conduct manual pill counts, obtain dried blood spots to confirm adherence, provide substance use disorder counseling, and obtain urine drug screens. At Study Visit 5, the investigators will conduct a semi-structured qualitative interview with participants in the PrEPsteps arm, which will be grounded in the Technology Acceptance Model, in order to understand the user response to PrEPSteps and the digital pill. All participants will complete the final follow-up assessment 3 months after Study Visit 5 (Study Visit 6).

PrEPSteps is a novel, smartphone-based behavioral intervention that delivers PrEP adherence messages in response to detected PrEP ingestion via an innovative digital pill. PrEPSteps comprises 1) an adaptation of LifeSteps, an evidence-based medication adherence behavioral intervention, with smartphone-delivered booster sessions, 2) messages of contingent reinforcement and corrective feedback, and 3) stimulant use screening, brief assessment, and referral to treatment. In this K23, the investigators will first refine and inform the specification of PrEPSteps with a series of focus groups. The investigators will next test the feasibility, acceptability and potential for an effect of PrEPSteps to boost PrEP adherence in a pilot randomized controlled trial of men who have sex with men (MSM) with stimulant use. Finally, the investigators will conduct qualitative interviews among participants who used PrEPSteps to understand the participant response to living with the intervention.

Participants receive the digital pills with Truvada, plus the PrEPsteps intervention that is programmed at the randomization study visit (Study Visit 2). Participants will use PrEPsteps and the digital pill to measure Truvada adherence for months 1-3.

Participants receive digital pills with Truvada alone. Participants will use digital pills with Truvada for months 1-3.

Smartphone-based adherence intervention based in 1) LifeSteps, 2) Contingent Reinforcement/Corrective Feedback, and 3) Screening Brief Intervention and Referral to Treatment (SBIRT).

The digital pill comprises a standard gelatin capsule with an integrated radiofrequency emitter that overencapsulates the desired medication (Truvada). When participants ingest the digital pill, the chloride ion gradient in the stomach activates the radiofrequency emitter which transmits direct evidence of medication ingestion to a wearable reader which relays this data to the participant's smartphone and cloud server.

Acceptability as determined by the mean score of the following questions during study visits (graded on a 1-10 scale): "How satisfied were you with PrEPsteps? How likely are you to recommend PrEPsteps to someone who needs PrEP? How likely are you to recommend PrEPsteps to someone who needs PrEP and uses stimulants?

Feasibility of PrEPstesps as determined by the mean number of times intervention was accessed by each study participant during the trial

Accuracy of digital pill in measuring PrEP adherence as compared to dried blood spot testing for tenofovir diphosphate

Inclusion Criteria: Cisgender MSM Moderate to severe non-alcohol substance use disorder Self-reported missed PrEP doses (> or equal to 2 doses in 1 week over past 3 months) HIV negative On PrEP or initiating PrEP Has qualifying laboratory testing: Cr clearance, HBV, liver function tests Owns a smartphone with Android or iOS Age 18 or older Exclusion Criteria: Non-English speaker HIV positive History of Crohn's disease or ulcerative colitis History of gastric bypass, bowel stricture History of GI malignancy or radiation to abdomen Unable/unwilling to ingest a digital pill Allergy to gelatin, silver or zinc (components of the digital pill) Does not qualify for PrEP (abnormal liver function, or Cr Clearance <60)