The Tablets, Ring, Injections as Options (TRIO) study: what young African women chose and used for future HIV and pregnancy prevention

Abstract

Introduction: Preventing HIV and unintended pregnancies are key global health priorities. To inform product rollout and to understand attributes of future multipurpose prevention technologies (MPT) associated with preference and use, we evaluated three placebo delivery forms: daily oral tablets, a monthly vaginal ring, and two monthly intramuscular injections in TRIO, a five-month study among young Kenyan and South African women.

Methods: HIV-negative, sexually active, non-pregnant women aged 18 to 30 were enrolled and randomized to use each placebo delivery form for one month (stage 1). Then, participants chose one product to use for two additional months (stage 2). We assessed safety, product ranking, choice, and use. We examined demographic and behavioural correlates of choice and, reciprocally, unwillingness to use in the future with logistic regression models.

Results: 277 women enrolled, 249 completed stage 1 and 246 completed stage 2. Median age was 23 years, 49% were Kenyan and 51% were South African. Three participants became pregnant during the study and one participant HIV-seroconverted. There were 18 product-related adverse events, six tablets-related, 11 ring-related, and one injection-related. After trying each product, 85% preferred a TRIO product over condoms. Injections were chosen most (64%, 95% confidence interval (CI) 58%, 70%; p < 0.001), and by more South Africans than Kenyans (odds ratio (OR) 2.01, 95% CI: 1.17, 3.43; p = 0.01). There was no significant difference in choosing tablets versus ring (21%, 95% CI: 16%, 26% vs. 15%, 95% CI: 11%, 20%; p = 0.11). Tablet and ring adherence, based on direct observations and self-reports, improved over time. However, participants' self-reported use of tablets did not match objective data from the electronic dose monitoring device. Participants were fully compliant with injections.

Conclusion: In this population at risk for HIV and pregnancy, all participants agreed to choose and use a placebo MPT delivery form. A majority of participants preferred TRIO products to male condoms, an existing MPT. Injections were most liked and best used, however, they are years away from reaching the clinics. In the meantime, expanding the availability of tablets and giving access to rings can begin to fulfill the promise of choice for HIV prevention technologies and inform the development of suitable delivery forms as MPT.

Keywords: Africa; HIV prevention; contraception; end-user research; multipurpose prevention technologies; product preference.

Figure 1

TRIO study flow chart. Product Key: I, Injectable; R, Ring; T, Tablet. TRIO study design, participants disposition and analytical sample. At enrolment into stage 1, participants were randomized to one of six product‐use sequences. Randomization was stratified by site and included blocks of size six to equally distribute the six treatment sequences.

Figure 2

Ranking of TRIO study products with condoms for both HIV and pregnancy prevention. After trying each study product for one month, participants (n = 249) were asked to rank the products and condoms in order of preference, assuming all products had the same effectiveness as male condoms to prevent HIV and unplanned pregnancy.

Figure 3

Product adherence during the TRIO study. Adherence was a multicomponent measure based on self‐reported use and direct observation of use during the study visits (initiation and return visit after 1 month of use). For injections, adherence was based on receiving two injections at the initiation visit by the study clinician. Adherence during stage 1 is shown for those who chose to use the product in stage 2 compared to those who did not chose to use the product in stage 2. Adherence improved during stage 2 for tablets (p = 0.04) and ring (p = 0.06). For tablets, objective use data was also available from Wisepill containers, which electronically track the opening of the tablet container (second set of bars from the left). Participants were considered adherent per Wisepill if the container was opened at least once per day for 80% of days during the month. For tablet use per Wisepill, there was a significant decrease in use over time (p = 0.002). *p < 0.05 †p < 0.10; p‐values from mixed‐effect logistic regression model.