Duo: A Phase IIIb Individual-Level Randomized Controlled Trial of an Integrated Strategy

To determine the efficacy of the 3P mHealth package on PrEP uptake among participants

PrEP uptake is defined as the proportion of enrolled participants who elect to initiate PrEP (with a documented PrEP dispensation by the site) at any time during the 52 weeks of follow-up. Participants who did not initiate PrEP before loss to follow-up will be classified as non-initiators. PrEP uptake will be assessed at Week 52 for each study arm with 95% confidence limits computed using the binomial distribution. A logistic regression model will be used to compare PrEP uptake between the study arms.

To determine the efficacy of the 3P mHealth package on PrEP adherence among participants

PrEP adherence is assessed at Weeks 20, 36 and 52 through biomedical testing for oral PrEP regimens and documentation of CAB-LA injection for CAB-LA. Adherence measures are described in Section 8.7. Participants on oral PrEP missing an assessment visit and with no PrEP dispensed at their most recent visit will be considered non-adherent. Also, participants who have not yet initiated PrEP at a visit will be considered non-adherent at that visit. The average PrEP adherence at a visit will be computed as the proportion of participants who are determined to be adherent at that visit by study arm. The associated 95% confidence limits will be computed using the binomial distribution. Generalized estimating equations (GEE) with a logit link function will be used to examine differences in adherence proportions between the 3P and Control arms at Weeks 20, 36 and 52, while accounting for potential correlation between PrEP adherence measures over time for each participant.

To assess doxycycline PEP uptake and associated factors

doxy-PEP uptake is defined as the proportion of participants dispensed doxy-PEP during the 52 weeks of study follow-up period. doxy-PEP uptake will be computed with 95% confidence limits at Week 52. Multivariable logistic regression models will be used to assess association between doxy-PEP uptake and factors including study group, demographic and behavioral characteristics.

To assess doxycycline PEP use and associated factors

doxy-PEP use will be assessed at Weeks 20, 36 and 52. Doxy-PEP use at an assessment visit will be computed as the proportion of participants reporting use following sex acts, reported at that visit. The corresponding 95% confidence limits will be computed based on the binomial distribution. Multivariable GEE models will be used to investigate possible associations between doxy-PEP use and factors including study group, demographic and behavioral characteristics.

To determine the acceptability and use of the 3P mHealth package in the intervention arm by site

Descriptive statistics will be used to summarize the acceptability and use of the 3P mHealth package in the intervention arm by site.

To compare the frequency, directionality, and reasons for PrEP regimen choice and switching, between arms

Descriptive statistics will be used to summarize the frequency, directionality, and reasons for PrEP regimen choice and switching by arm. Generalized linear models will be used to assess differences in these descriptive summaries between the study arms. Reasons for PrEP regimen choice and switching obtained from qualitative interview data will be listed by arm.

To evaluate demographic, behavioral, and attitudinal factors associated with choice of PrEP regimen

Multivariable logistic regression models will be used to separately assess associations between each PrEP regimen choice and demographic, behavioral, and attitudinal factors.

To determine the efficacy of the 3P mHealth package on prevention-effective adherence

* The proportion of enrolled participants with incident STI infection will be computed with 95% confidence limits at Weeks 20, 36 and 52 by study arm. * The proportion of enrolled participants with incident HIV infection will be computed at Weeks 20, 36 and 52 by study arm. * The proportion of enrolled participants reporting HIV risk based on self-reported sexual behavior and HIV status of sexual partner will be computed at Weeks 20, 36 and 52 by study arm. * The proportion of enrolled participants who are determined to be PrEP adherent and potentially at HIV risk (based on incident STI, self-reported sexual behavior and HIV status of partners) will be computed with 95% confidence limits at Weeks 20, 36 and 52 by study arm. GEE models with a logit link function will be used to compare the proportions between the study arms