Interventions to reengage people living with HIV who are lost to follow-up from HIV treatment programs: A systematic review and meta-analysis

Background
Optimizing services to facilitate engagement and retention in care of people living with HIV (PLWH) on antiretroviral therapies (ARTs) is critical to decrease HIV-related morbidity and mortality and HIV transmission. We systematically reviewed the literature for the effectiveness of implementation strategies to reestablish and subsequently retain clinical contact, improve viral load suppression, and reduce mortality among patients who had been lost to follow-up (LTFU) from HIV services.

Methods and findings
We searched 7 databases (PubMed, Cochrane, ERIC, PsycINFO, EMBASE, Web of Science, and the WHO regional databases) and 3 conference abstract archives (CROI, IAC, and IAS) to find randomized trials and observational studies published through 13 April 2020. Eligible studies included those involving children and adults who were diagnosed with HIV, had initiated ART, and were subsequently lost to care and that reported at least one review outcome (return to care, retention, viral suppression, or mortality). Data were extracted by 2 reviewers, with discrepancies resolved by a third. We characterized reengagement strategies according to how, where, and by whom tracing was conducted. We explored effects, first, among all categorized as LTFU from the HIV program (reengagement program effect) and second among those found to be alive and out of care (reengagement contact outcome). We used random-effect models for meta-analysis and conducted subgroup analyses to explore heterogeneity. Searches yielded 4,244 titles, resulting in 37 included studies (6 randomized trials and 31 observational studies). In low- and middle-income countries (LMICs) (N = 16), tracing most frequently involved identification of LTFU from the electronic medical record (EMR) and paper records followed by a combination of telephone calls and field tracing (including home visits), by a team of outreach workers within 3 months of becoming LTFU (N = 7), with few incorporating additional strategies to support reengagement beyond contact (N = 2). In high-income countries (HICs) (N = 21 studies), LTFU were similarly identified through EMR systems, at times matched with other public health records (N = 4), followed by telephone calls and letters sent by mail or email and conducted by outreach specialist teams. Home visits were less common (N = 7) than in LMICs, and additional reengagement support was similarly infrequent (N = 5). Overall, reengagement programs were able to return 39% (95% CI: 31% to 47%) of all patients who were characterized as LTFU (n = 29). Reengagement contact resulted in 58% (95% CI: 51% to 65%) return among those found to be alive and out of care (N = 17). In 9 studies that had a control condition, the return was higher among those in the reengagement intervention group than the standard of care group (RR: 1.20 (95% CI: 1.08 to 1.32, P < 0.001). There were insufficient data to generate pooled estimates of retention, viral suppression, or mortality after the return.

Conclusions
While the types of interventions are markedly heterogeneity, reengagement interventions increase return to care. HIV programs should consider investing in systems to better characterize LTFU to identify those who are alive and out of care, and further research on the optimum time to initiate reengagement efforts after missed visits and how to best support sustained reengagement could improve efficiency and effectiveness.