Discussion
primary retention
Of participants enrolled at PC0, 73% had at least one follow-up visit completed (Table Retention in PopART was lower than that achieved in the Botswana Combination Prevention Project (BCPP). BCPP was a smaller CRT, conducted in a more rural setting (15 villages in Botswana) between 2013 and 2018 that evaluated the effect of enhanced provision of ART and voluntary male medical circumcision on population level HIV incidence. The CRT design in PopART and BCPP was comparable with study interventions provided community-wide and a cohort of community members randomly selected for more intensive follow-up for primary end point assessment. Study interventions were context specific and similar to PopART. In BCPP, 12,600 participants were followed up for HIV testing at 12 and approximately 29 months. Overall, > 95% of participants enrolled into the study cohort were successfully followed up at either 12 or 29 months [The association between HIV status and retention produced some interesting findings. Participants confirmed as HIV positive on baseline laboratory testing were significantly less likely to be retained. Far fewer participants self-reported HIV positive status at baseline than those confirmed on laboratory HIV testing. Participants self-reporting HIV positive at baseline were conversely more likely to be retained compared to those reporting “not knowing their status” or “never having tested.” The difference in frequency of HIV positive status between laboratory and self-report is likely to reflect a combination of “not knowing HIV status” and under-reporting of known HIV-positive status by participants, a trend supported by previously published data from the PC which showed that a considerable number of participants who were on ART self-reported they were HIV negative [Among participants defined as having permanently left the study (study “withdrawal”), the most common reason documented by the research team was “moving out of the study catchment” area (66%). This was despite “intention to remain in community over the 3-year period of study activities” being a study eligibility criterion. This suggests that participants who exited the community during the trial period were likely to have done so without prior long-term planning. In a separate PopART publication, social cohesion within study communities as the result of complex community dynamics (such as availability of social amenities, crime, poverty and drug use) was related to migration in and out of study communities. Where information is available, these factors should be considered in the choice of study communities and once the study is implemented a better understanding of these issues could assist to focus retention interventions [There has been extensive research into the effectiveness of retention strategies in longitudinal studies. A systematic review of 141 cohort studies from 28 countries [The need for disclosure by participants about study participation and support for participants within their households and communities is recognized as critical for retention [PopART has provided a unique opportunity to evaluate participant retention in the largest HIV prevention CRT to date. The community-based follow-up, over a long period of time (3–4 years), with inclusion of urban and peri-urban areas is also novel and contributes to the scientific relevance of this study. Standardized retention activities with active participant follow-up and careful documentation of these efforts, together with publications communicating associated outcomes from the study, have enabled us to complete a rigorous evaluation of participant retention. However, limitations for consideration exist. An approximately equal number of men and women were randomly selected for study enrolment. Men, however, were harder to access as they were often not present in the house and had higher rates of refusal to participate in the study. We unfortunately do not have systematic data on participants who refused to participate in the study. Men were more likely to be lost to follow-up and having more women in the cohort may therefore have increased overall retention. Similarly, reporter bias and “social desirability” among participants may have led to under-reporting of social activities such as alcohol and drug use which in turn affected the multivariable analysis. Conversely with the very large sample size, there becomes a high likelihood of statistically significant associations between independent variables and study outcomes even when differences in the proportions with the outcome are small across variable categories, and this should be considered when reviewing the multivariable analysis. Although the 21 communities in Zambia and South Africa included in PopART are representative of many high HIV burden communities, contextual factors (e.g., urban vs. peri-urban) likely play a significant role in determining participant retention. The findings of this study therefore need to be reviewed carefully when conducting similar studies in other settings. Our primary retention outcome was defined as the total number of annual visits where a study questionnaire was completed. For the participant visit to contribute to primary endpoint measurement laboratory-based HIV testing needed to be completed. There were a limited number of retained participants for whom no laboratory-based HIV testing was done for a variety of reasons including failure to complete phlebotomy and hemolyzed samples. Evaluation of this HIV testing pathway was outside the focus of this paper; however, challenges with testing should also be carefully considered by researchers implementing community-based trials.