Adaptive Strategies for Retention in Care among Persons Living with HIV

Abstract

Background: Optimizing retention in human immunodeficiency virus (HIV) treatment may require sequential behavioral interventions based on patients' response.

Methods: In a sequential multiple assignment randomized trial in Kenya, we randomly assigned adults initiating HIV treatment to standard of care (SOC), Short Message Service (SMS) messages, or conditional cash transfers (CCT). Those with retention lapse (missed a clinic visit by ≥14 days) were randomly assigned again to standard-of-care outreach (SOC-Outreach), SMS+CCT, or peer navigation. Those randomly assigned to SMS or CCT who did not lapse after 1 year were randomly assigned again to either stop or continue the initial intervention. Primary outcomes were retention in care without an initial lapse, return to the clinic among those who lapsed, and time in care; secondary outcomes included adjudicated viral suppression. Average treatment effect (ATE) was calculated using targeted maximum likelihood estimation with adjustment for baseline characteristics at randomization and certain time-varying characteristics at rerandomization.

Results: Among 1809 participants, 79.7% of those randomly assigned to CCT (n=523/656), 71.7% to SMS (n=393/548), and 70.7% to SOC (n=428/605) were retained in care in the first year (ATE: 9.9%; 95% confidence interval [CI]: 5.4%, 14.4% and ATE: 4.2%; 95% CI: -0.7%, 9.2% for CCT and SMS compared with SOC, respectively). Among 312 participants with an initial lapse who were randomly assigned again, 69.1% who were randomly assigned to a navigator (n=76/110) returned, 69.5% randomly assigned to CCT+SMS (n=73/105) returned, and 55.7% randomly assigned to SOC-Outreach (n=54/97) returned (ATE: 14.1%; 95% CI: 0.6%, 27.6% and ATE: 11.4%; 95% CI: -2.2%, 24.9% for navigator and CCT+SMS compared with SOC-Outreach, respectively). Among participants without lapse on SMS, continuing SMS did not affect retention (n=122/180; 67.8% retained) versus stopping (n=151/209; 72.2% retained; ATE: -4.4%; 95% CI: -16.6%, 7.9%). Among participants without lapse on CCT, those continuing CCT had higher retention (n=192/230; 83.5% retained) than those stopping (n=173/287; 60.3% retained; ATE: 28.6%; 95% CI: 19.9%, 37.3%). Among 15 sequenced strategies, initial CCT, escalated to navigator if lapse occurred and continued if no lapse occurred, increased time in care (ATE: 7.2%, 95% CI: 3.7%, 10.7%) and viral suppression (ATE: 8.2%, 95% CI: 2.2%, 14.2%), the most compared with SOC throughout. Initial SMS escalated to navigator if lapse occurred, and otherwise continued, showed similar effect sizes compared with SOC throughout.

Conclusions: Active interventions to prevent retention lapses followed by navigation for those who lapse and maintenance of initial intervention for those without lapse resulted in best overall retention and viral suppression among the strategies studied. Among those who remained in care, discontinuation of CCT, but not SMS, compromised retention and suppression. (Funded by National Institutes of Health grants R01 MH104123, K24 AI134413, and R01 AI074345; ClinicalTrials.gov number, NCT02338739.).

Figure 1.. Trial Profile and Consort Diagram, Reflecting SMART Design.

In Stage 1 (n=1809), we compared standard of care (SOC, routine education and counseling) with the addition of Short Message Service (SMS) text messages or of conditional cash transfers (CCT) of 400 Kenyan shillings for making appointments. In Stage 2a (n=312), we compared standard-of-care outreach (composed of phone and/or in-person contact attempts within the first 72 hours of missing a visit) with addition of either SMS+CCT or assignment to a navigator. In Stage 2b, those without a lapse in the first year while receiving SMS (n=389) and CCT (n=517) were randomly assigned again to stop or continue. We evaluated effects on retention and HIV ( human immunodeficiency virus) RNA (ribonucleic acid) outcomes. ART denotes antiretroviral therapy; RR, rerandomization; and SMART, sequential multiple assignment randomized trial.

Figure 2.. Kaplan–Meier Plots of Stage 1 and Stage 2 Outcomes.

Panel A shows time to first retention lapse (clinic visit missed by 14 or more days) after initial random assignment among all participants (Stage 1, n=1809). Panel B shows time to return to clinic after rerandomization among those with a retention lapse in year 1 (Stage 2a, n=312). Lower panels show time to first lapse after rerandomization among participants with no lapse in year 1 on Short Message Service (SMS) text intervention (Panel C; Stage 2b, n=389) or conditional cash transfers for on-time visit (CCT) intervention (Panel D; Stage 2b, n=517). Effect estimates shown are absolute differences in cumulative incidence of event by 1 year. The widths of the confidence intervals (CIs) have not been adjusted for multiplicity; therefore, the CIs should not be used to reject or not reject effects. SOC denotes initial standard of care (routine education and counseling); and SOCO, standard-of-care outreach (standard of care following a retention lapse).

Figure 3.. Stage 2a and 2b Outcomes.

Figure shows mean proportion of follow-up time engaged in care from rerandomization to study close at year 2 (Panel A) and proportion with treatment success (adjudicated viral suppression) at study close (Panel B) among participants with a retention lapse in year 1 (Stage 2a, n=312) and among participants with no lapse in the first year on the Short Message Service (SMS) text message intervention (Stage 2b, n=389) and on the conditional cash transfers for on-time visits (CCT) intervention (Stage 2b, n=517). Effect estimates shown are absolute differences in mean outcomes (average treatment effect [ATE] adjusted for baseline characteristics and thus not equal to crude differences). The widths of the confidence intervals (CIs) have not been adjusted for multiplicity; therefore, the CIs should not be used to reject or not reject effects. SOCO denotes standard-of-care outreach (standard of care following a retention lapse).

Figure 4.. Stage 2a Outcomes Stratified by Stage 1 Interventions.

Figure shows mean proportion of follow-up time engaged in care from rerandomization to study close at year 2 (Panel A) and proportion with treatment success (adjudicated viral suppression) at study close (Panel B) among participants with a retention lapse in year 1 (Stage 2a, n=312), stratified by initial (Stage 1) randomized treatment assignment. Effect estimates shown are absolute differences in mean outcomes (average treatment effect [ATE] adjusted for baseline characteristics and thus not equal to crude differences). The widths of the confidence intervals (CIs) have not been adjusted for multiplicity; therefore, the CIs should not be used to reject or not reject effects. CCT denotes conditional cash transfers for on-time visits; SMS, Short Message Service text message intervention; SOC, initial standard of care (routine education and counseling); and SOCO, standard-of-care outreach (standard of care following a retention lapse).

Figure 5.. Effects of the 14 Active Sequenced Adaptive Strategies Compared with SOC.

Figure shows standard of care (SOC) routine education and counseling initially, escalation to standard-of-care outreach (SOCO [standard of care following a retention lapse]) or those with a lapse, and maintenance of SOC for those with no lapse during the first year of follow-up (SOC > SOCO/Continue). Effects on mean proportion of follow-up time engaged in care are shown in Panel A and probability of treatment success (adjudicated viral suppression) at the end of follow-up year 2 in Panel B. Each strategy is expressed as three stages: the initial intervention, the intervention assigned in event of a lapse in year 1, and the intervention assigned at the end of year 1 if no lapse occurs. For example, conditional cash transfers for on-time visits (CCT) > SOCO > STOP refers to an initial CCT intervention, followed by SOCO should a lapse occur, and by discontinuation of the cash transfer should no lapse occur in the first year. Point estimates of the average treatment effects (markers) with 95% confidence intervals (bars) are shown. The widths of the confidence intervals have not been adjusted for multiplicity; therefore, they should not be used to reject or not reject effects. SMS denotes Short Message Service text message intervention.