Study design and procedure:
The TRUST / RV 368 study abbreviated TRUST has been enrolling SGM in Nigeria since 2013. TRUST enrolled and provided daily oral PrEP for SGM in a single site, open-label, prospective cohort study in Abuja, Nigeria. The respondent driven-sampling method of SGM recruitment for TRUST has been previously described (23,24). Two approaches were used to introduce PrEP: Peer-to-peer introduction from the community (community-based), via the popular opinion leaders, and provider-initiated introduction from the clinic (clinic-based). SGM introduced to PrEP by the community-based method were screened and assessed for eligibility for the TRUST study initially, and if eligible and interested, they completed the PrEP study willingness questionnaires before they were assessed for eligibility for this study. For the clinic-based PrEP approach, health care providers discussed PrEP with all SGM attending the routine clinics and offered the PrEP study willingness questionnaires to those interested before the eligibility assessment for this study. This study’s enrollment commenced in April 2018 and ended in May 2019, and the follow-up visits (at months 1, 3, 6, and 9) continued until June 2020.
Study eligibility criteria:
The participants who met the TRUST criteria and had substantial HIV risk were included in this study. These criteria included: 1) being at least 16 years old (considered able to access sexual and reproductive health and HIV care and research without parental consent in Nigeria) (25), 2) assignment of male sex at birth, 3) history of receptive or insertive anal intercourse with another male in the prior 12 months, and 4) providing informed consent in the local language or English. At enrollment, they needed to present a valid study coupon, confirmed not living with HIV, and are willing to consent to the use of daily oral PrEP and the collection of biological specimens at each study visit. Participants were at substantial risk of HIV acquisition if they reported any of the following within the past three months at enrolment; condomless anal or vaginal intercourse, had more than one sexual partner, intercourse with a partner of unknown HIV status, shared injection materials or had a history of STI diagnosis.
Data collection:
Excluding the baseline, there were four study visits at months one, three, six, and nine. Behavioral information was collected at baseline, month 3, and month 9 visits through in-person interviews. Clinical providers collected serum, rectal swabs, and urine samples for STI testing: (HIV, urethral and rectal Neisseria gonorrhea [GN], and Chlamydia trachomatis [CT]). HIV testing was done with parallel assays using the Alere Determine HIV-1/ 2 (Abbott Laboratories, Chicago, IL) and HIV 1/2 STAT- Pak assays (Chembio Diagnostic system Inc, Medford, NY). Aptima Combo 2 Assay test kits (Hologic, Marlborough, MA) were used for the detection of ribosomal RNA of GN via the nucleic acid amplification test methods.
Definition of study variables:
Outcome variables: These were behavioral outcomes and sexually transmitted infections.
The behavioral outcome was based on responses to two behavioral questions asked during the in-person interviews at baseline, months 3, and 9 in both pre-PrEP and PrEP periods (defined below), as follows: “Now think about the last time you had anal sex with a male partner. Was a condom used at that time?” (Variable name: condomless anal intercourse with last male partner [CAI]). The second question was “Do you currently have two or more regular male sexual partners at this time?” (Variable name: concurrency). The possible responses for both questions were 1= “Yes”, 0= “No”, “I do not know”, or declined to respond. For this analysis, “I do not know” and declining to respond were categorized as declined to respond and treated as missing variables.
For the STI outcome, polymerase chain reaction (PCR)-diagnosed STIs for each of rectal gonorrhea, rectal chlamydia, urethral gonorrhea, and urethral chlamydia were assessed at every visit after enrollment. Each of these was dichotomized into a 1 = "positive” or 0= “negative”.
Exposure variables: PrEP period (Time)
This was defined as pre-PrEP period and PrEP periods. The pre-PrEP period was between February 15, 2016, and the day each participant initiated PrEP. The mid-February 2016 date was selected for two reasons. First, to have an adequate time for pre-PrEP participant data collection, and secondly, to establish a minimum two-year washout period for existing study participants who might have taken PrEP in the past. The PrEP period was between the day each participant initiated PrEP and the last day of PrEP use. The last day of PrEP use was estimated from the last PrEP prescription uptake date.
Covariates
Demographic variables including age (binary variable [16-24 and ≥25 years]), and employment status (employed or unemployed) were assessed at enrollment and every three months. Other demographic variables include education level (≤ high school or > high school), marital status (never married or ever married), gender identity (cisgender man, transgender woman, or non-binary/other), and sexual orientation (homosexual, bisexual or heterosexual) were assessed at enrollment only.
Behavioral variables such as “number of days alcohol taken in the past 30 days” (0-2= “No”, ≥ 3= “Yes”) were assessed at baseline and 9 months.
Ethical Approval:
Ethical approval was obtained from the Institutional Review Board of the University of Maryland Baltimore and the Federal Capital Territory Health Research Committee, Abuja, Nigeria.
Statistical Analysis:
We conducted a bivariate analysis for the baseline characteristics of the cohort during the Pre-PrEP period. Furthermore, we performed a bivariate analysis with each of the self-reported behavioral outcomes (CAI and concurrency) to identify potential confounders for inclusion in the final multivariable analysis. Covariates that resulted in a greater than 10% change in the regression coefficient estimate of the primary exposure (study time) when added to the conditional logistic regression were considered confounders.
For multivariable analysis, we performed a pre and post-PrEP intervention analysis. This analytical approach minimized confounding that would have otherwise occurred with control groups. The PrEP intervention was defined as the date each participant initiated PrEP. We compared participants who had been in the TRUST study on or before February 15, 2016, with themselves after initiating PrEP up until they completed their PrEP medication thereby serving as self-controls in this analysis. We performed a conditional logistic regression, using the unique study identification as the strata variable to estimate the odds ratio and 95% confidence interval between the study periods and STI prevalent cases and behavioral outcomes. In addition, we performed an adjusted conditional logistic regression for self-reported behavioral outcomes, based on the potential confounding variables identified from the bivariate analysis. We could not perform a similar analysis for the STI outcome due to an inadequate number of events to power the analysis. For all analyses, a complete case analysis method for all exposure and outcome variables was utilized. We used SAS version 9.4 (SAS Institute Inc., Cary, NC, USA) and STATA version 15.0 (College Station, TX, USA) for all analyses.