ADHERENCE TO THE DAPIVIRINE VAGINAL RING AMONG WOMEN IN AFRICA: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Introduction: Despite the availability of HIV preventive measures, new HIV infections are still on the rise. The Dapivirine Vaginal Ring (DVR), a silicone circular ring, continuously distributes Dapivirine into the vagina to prevent HIV infection. The objective of this systematic review is to summarize the evidence on adherence to DVR for HIV-1 prevention among women in Africa and to describe the factors associated with adherence. Methods and Analysis: This thesis comprises two separate publishable manuscripts (a published protocol with Health Science Reports and an article currently in press with PLOS Global Public Health). The core parts of this thesis include: chapter one, where a comprehensive summary of evidence on HIV, Pre-Exposure Prophylaxis, Dapivirine Vaginal Ring, adherence, and other components is described. There is limited evidence on the extent of DVR adherence among females in Africa, as well as factors associated with existing adherence. This formed the basis for the study that is conducted in this thesis. In chapter two, details on how the thesis was conducted are presented. That is: a systematic review of studies in which DVR was used to prevent HIV-1 in African women. We searched MEDLINE, Global Health, CINAHL, and EMBASE from database inception to December 2024. We included observational studies and randomized trials of females between 16 and 45 years of age, resident in Africa, who have used the DVR. Our primary outcome was adherence to DVR explored as women adhering, mean adherence, and visit/rings adhering. Pairs of reviewers independently screened for eligible studies and extracted relevant data. We performed a random-effects meta-analysis of proportions and mean for DVR adherence. The certainty of the evidence was assessed using the GRADE approach.

Results and Discussion: In chapter three, we presented the study findings according to the study-specific objectives. Chapter four of the thesis discusses a summary of the methodological issues, future directions, and review conclusions will be presented. As such, our search retrieved 217 records, of which 15 published between 2016 and 2024 were found. Across the seven included studies, there were a total of 2,424 DVR women users reported in four studies, 1,552 participants in the two studies reporting mean adherence, 27,904 follow-up visits, and 14,034 rings distributed. Adherence to the DVR among women was generally high, with a pooled estimate of 83%, although the certainty of evidence was very low. Mean adherence scores also suggested good adherence, with a pooled mean of 3.34 (95% CI: 3.00–3.67). There were 74% (95% CI: 74–75%) of rings used well and 89% (95% CI: 89–90%) of visits with adherence. Factors influencing adherence included individual characteristics (e.g., education level, country), partner-related aspects (e.g., partner feeling the ring during sex), ring-related challenges (e.g., difficulty inserting the ring), and environmental influences (e.g., discussing the study with non-study staff). Conclusion The evidence suggests generally good adherence to the DVR, which may enhance its effectiveness in reducing HIV infections in real-world settings; however, the certainty of this evidence is low. Given this limitation, we recommend that DVR use be accompanied by additional prevention methods, such as condoms. We also encourage further implementation research, particularly individual patient data meta-analyses, to assess adherence more accurately. These efforts can provide critical insights for developing targeted strategies to improve adherence and generate comprehensive pooled estimates to better inform practice and policy. Protocol Registration This study was registered on Prospero (CRD42024593018).