Sequential Strategies to Reach and Reengage Individuals after Lapses from HIV Care in Zambia

ABSTRACT Treatment lapses remain one of the most enduring challenges to viral suppression in Africa. These individuals have higher rates of viremia (~70%), morbidity, and mortality, and now represent the majority of those hospitalized with advanced HIV. Even among those who return to care, 30-50% have repeat lapses due to

ongoing challenges with care such competing obligations, travel/mobility, clinic-based, or psychosocial barriers. Effective strategies for durably reengaging individuals with treatment lapses must address two steps: they must first be brought back into care, but after return, person-centered strategies are needed to prevent repeat lapses

and keep them reengaged long-term. Navigation (NAV) and community-based medication delivery (CB-Med) are strategies that have been found to improve outcomes among those newly initiating or stable on ART, and our preliminary data indicates their complementary mechanisms hold promise to address key challenges at both

the return and reengage stages. NAV offers a flexible approach to tailor outreach, care coordination, and psychosocial support to match individuals' unique barriers to care. Leveraging navigators to provide ongoing CB-Med efficiently adds instrumental support to further reduce challenges with medication access. Still, rigorous

evidence on the use, timing, and optimal combinations of NAV and CB-Med after treatment lapses is lacking. For example, offering NAV+CB-Med may improve rates of ART re-initiation, but this may not translate to better longer-term outcomes if it is stopped after return and individuals then receive the same care that previously

failed. We propose a sequential multiple assignment randomized trial (SMART) among 1270 individuals who are >30 days late for an appointment to assess different sequential combinations of return to care and reengagement strategies. We randomize participants in the first-stage to receive (1) routine phone outreach only (standard of

care [SOC]) or (2) NAV+CB-Med for rapid ART re-initiation in the community and reentry support. Among those who return to care, we re-randomize them in the second-stage to: (1) routine care and counseling after return (RCC [SOC]), (2) NAV only after return, or (3) NAV+CB-Med after return. In Aim 1a, we compare phone outreach

only vs. NAV+CB-Med on time to ART re-initiation and return to care. In Aim 1b, among individuals who return, we compare RCC, NAV alone, and NAV+CB-Med on retention in care after return (time to missing a pharmacy refill by >14 days). In Aim 2, we assess the overall effectiveness and cost-effectiveness of the six sequential

combination return-and-reengage strategies embedded within the SMART design on viral suppression at 18- months after initial randomization (primary outcome). Lastly, in Aim 3 we conduct a mixed-methods evaluation to understand implementation (e.g., reach, adoption, fidelity, acceptability), mechanisms of action, and potential

for sustainability among diverse stakeholders (e.g., participants, health care workers, public health officials). This proposal advances a high-priority research agenda to identify the most effective and efficient combination strategies to both return individuals with treatment lapses to care and then keep them reengaged.