Early access to antiretroviral therapy versus standard of care among HIV‐positive participants in Eswatini in the public health sector: the MaxART stepped‐wedge randomized controlled trial

Abstract

Introduction: The WHO recommends antiretroviral treatment (ART) for all HIV-positive patients regardless of CD4 count or disease stage, referred to as "Early Access to ART for All" (EAAA). The health systems effects of EAAA implementation are unknown. This trial was implemented in a government-managed public health system with the aim to examine the "real world" impact of EAAA on care retention and viral suppression. Methods: In this stepped-wedge randomized controlled trial, 14 public sector health facilities in Eswatini were paired and randomly assigned to stepwise transition from standard of care (SoC) to EAAA. ART-na€ ıve participants ≥18 years who were not pregnant or breastfeeding were eligible for enrolment. We used Cox proportional hazard models with censoring at clinic transition to estimate the effects of EAAA on retention in care and retention and viral suppression combined. Results: Between September 2014 and August 2017, 3405 participants were enrolled. In SoC and EAAA respectively, 12month HIV care retention rates were 80% (95% CI: 77 to 83) and 86% (95% CI: 83 to 88). The 12-month combined retention and viral suppression endpoint rates were 44% (95% CI: 40 to 48) under SoC compared to 80% (95% CI: 77 to 83) under EAAA. EAAA increased both retention (HR: 1Á60, 95% CI: 1Á15 to 2Á21, p = 0.005) and retention and viral suppression combined (HR: 4.88, 95% CI: 2.96 to 8.05, p < 0.001). We also identified significant gaps in current health systems ability to provide viral load (VL) monitoring with 80% participants in SoC and 66% in EAAA having a missing VL at last contact. Conclusions: The observed improvement in retention in care and on the combined retention and viral suppression provides an important co-benefit of EAAA to HIV-positive adults themselves, at least in the short term. Our results from this "real world" health systems trial strongly support EAAA for Eswatini and countries with similar HIV epidemics and health systems. VL monitoring needs to be scaled up for appropriate care management.

Longitudinal analysis of client appointment adherence under Universal Test and Treat strategy: A stepped‐wedge trial

“…These findings are reassuring given the limited existing literature on the impact of UTT on client adherence and retention. The primary study analysis showed improvements in client retention in care upon UTT implementation compared with standard of care [3]. The primary study analysis also determined that factors including lack of social support, care delivery, drug side effects and employment issues contributed to loss to follow‐up [4], and there were no significant differences in patient satisfaction between UTT and standard of care arms [5].…”

“…Details on the MaxART Early Access to ART for All implementation study have been described previously [3]. In brief, this 3‐year stepped‐wedge randomized trial had open enrolment for all ART‐naïve adults aged ≥ 18 years across 14 government‐managed health clinics in Eswatini's Hhohho Region from September 2014 to August 2017.…”

Universal test and treat in relation to HIV disease progression: results from a stepped‐wedge trial in Eswatini

“…Details of the MaxART Early Access to ART for All implementation study have been published previously [9–12]. In brief, this 3‐year stepped‐wedge randomized trial had open enrolment for all adults ≥ 18 years old across 14 public sector‐managed health clinics in Eswatini's Hhohho Region from September 2014 to August 2017.…”

Estimating the natural indirect effect and the mediation proportion via the product method

“…For example, if inflammation were to be confirmed as an important mediator of the obesity–lethal prostate cancer relationship, new approaches to the prevention, prediction, and the treatment of prostate cancer would likely emerge [ 3 ]. As another example, the anti-retroviral intervention referred to as “Early Access to ART for All” (EAAA) was found effective to improve the retention in care compared to the standard of care among HIV-positive patients in the MaxART study [ 4 ]. If we can identify an important mediator in the pathway between the intervention and HIV care retention, new strategies targeting the mediator may be developed to further improve outcomes.…”

“…Then, we describe our Monte Carlo simulation study that investigates the performance of the point and interval estimators for NIE and MP, and report our findings. To illustrate the product method, we study how much the effect of an EAAA intervention on 12-month retention is mediated by the 6-month visit adherence in the MaxART study [ 4 ]. Finally, we offer a brief discussion.…”