Condoms

Beginning November 5, 2012, heterosexual HIV-1-serodiscordant couples were enrolled in a prospective, open-label, implementation science-driven study of ART and PrEP for HIV-1 prevention (the Partners Demonstration Project, Clinicaltrials.gov NCT02775929). The overall goal was to evaluate a scalable, integrated, and pragmatic delivery approach for ART and time-limited PrEP, in combination with targeted counseling, brief adherence promotion, and frequency of follow-up designed to reflect approaches suitable for public health settings in East Africa. A sample size of 1,000 couples was chosen to provide a robust evaluation of the integrated ART and PrEP delivery strategy, across a diversity of clinical research sites. Couples were recruited using community outreach methods by four clinical care and research sites in Kenya (Kisumu and Thika) and Uganda (Kabwohe and Kampala). Recruitment strategies included working with voluntary counseling and testing centers, antenatal clinics and programs for prevention of mother-to-child HIV-1 transmission, referrals from HIV-1 care providers, including those performing testing of partners of known HIV-1 infected individuals engaged in HIV-1 care, and community promotion activities for couples’ testing.
Eligible couples were ≥18 y of age, sexually active, and intending to remain as a couple. At the time of enrollment, HIV-1 seronegative partners had never used PrEP, had normal renal function (defined as an estimated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation), were not infected with hepatitis B virus, and were not pregnant or breastfeeding. At enrollment, HIV-1 seropositive partners were not using ART; so as not to have the research process detract from immediate clinical need for ART, couples were excluded if the HIV-1-infected partner had WHO stage III or IV HIV-1 disease conditions. In addition, in order to recruit a population at higher risk for HIV-1 infection, a validated, empiric risk scoring tool was applied, and couples with a score ≥5 (out of a maximum of 12) were eligible for enrollment; in prior studies of HIV-1-serodiscordant couples, a score ≥5 was associated with an HIV-1 incidence in excess of 3%–4% per year [11 (link)]. For calculating the score, characteristics assessed at the time of screening included age of the HIV-1-uninfected partner, number of children in the partnership, circumcision status of HIV-1-uninfected men, whether the couple was cohabitating, whether the couple had had sex unprotected by a condom in the prior month, and the plasma HIV-1 RNA level in the HIV-1-infected partner. There was no obligation for couples to commit to initiating ART or PrEP as part of study eligibility. Ineligible couples were referred for standard of care HIV-1 prevention and treatment services.

Fifteen studies reported multiple associations of beliefs related to different adherence measurements (details reported in Table 1). Where the choice was between adherence measures, the most objective measure was selected for the meta-analysis. Therefore, electronic monitoring of adherence [20] and prescription redemption data [16] were chosen over self-report. Where data was presented for both ‘on demand’ and prophylactic medications, data for the prophylactic medication data were chosen [21] (link), [22] , for consistency with medications prescribed for other long-term conditions. In studies where cross-sectional and longitudinal data were both available, longitudinal data was used within the analysis [21] (link), [23] (link)–[26] (link). Where one group provided cross-sectional data at multiple timepoints, the timepoint with the fewest missing data points was selected [27] (link). If the choice was between two self report measures of adherence, we used the more commonly used measure. Thus the Morisky Medication Adherence Scale (MMAS) was chosen over the Brief Medication Questionnaire [28] (link) and the ACTG adherence measure was used over the Walsh VAS scale [29] (link). Where patients within a sample were taking multiple medications and individual associations were provided for each medication [30] , [31] (link), the mean association was used within the meta-analysis but individual effect sizes are reported in Table 1 to facilitate comparison. Where data on two samples are reported within the same study [32] (link), [33] (link) we included both associations within the analysis.

This cross-sectional study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. Adults born very preterm (gestational age <32 weeks) or families of very preterm infants currently in the neonatal intensive care unit (NICU) or having graduated from the NICU in the last 5 years were included from across Canada and the United Kingdom. The study was approved by the IWK Health Research Ethics Board, and all participants provided electronically signed written informed consent.
The study was planned in 2 phases. Phase 1, a pilot feasibility study, aimed to test our study questionnaire and provided an opportunity to modify any logistic or methodological issues. Phase 2, a formal study of values and preferences, used our pretested interview questionnaire to describe the variability in health-related values and preferences of former preterm infants and families concerning prophylactic use of COX-Is.

The outcome measures included (1) relative importance of clinical outcomes; (2) willingness to use each COX-I when presented as the only option; (3) preference for using prophylactic hydrocortisone vs indomethacin; (4) willingness to use any of the COX-Is when all 3 options are available; and (5) relative importance of having family values and preferences included in decision-making. The qualitative component of the interview attempted to identify themes related to the choice of prophylaxis based on participants’ perceptions of the therapeutic value of each COX-I.