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.

ObjectivesCurrent WHO guidelines recommend the treatment of all HIV‐infected individuals with antiretroviral therapy (ART) to improve survival and quality of life, and decrease infection of others. MaxART is the first implementation trial of this strategy embedded within a government‐managed health system, and assesses mortality as a secondary outcome. Because primary findings strongly supported scale‐up of the ‘treat all’ strategy (hereafter Treat All), this analysis examines mortality as an additional indicator of its impact.MethodsMaxART was conducted in 14 Eswatinian health clinics through a clinic‐based stepped‐wedge design, by transitioning clinics from then‐national standard of care (SoC) to the Treat All intervention. All‐cause, disease‐related, and HIV‐related mortality were analysed using the Cox proportional hazards model, censoring SoC participants at clinic transition. Median follow‐up time among study participants was 292 days. There were 36/2034 deaths in SoC (1.77%) and 49/1371 deaths in Treat All (3.57%).ResultsBetween September 2014 and August 2017, 3405 participants were enrolled. In SoC and Treat All interventions, respectively, the multivariable‐adjusted 12‐month all‐cause mortality rates were 1.42% [95% confidence interval (CI): 0.66–2.17] and 1.60% (95% CI: 0.78–2.40), disease‐related mortality rates were 1.02% (95% CI: 0.40–1.64) and 1.10% (95% CI: 0.46–1.73), and HIV‐related mortality rates were 1.03% (95% CI: 0.40–1.65) and 0.99% (95% CI: 0.40–1.58). Treat All had no impact on all‐cause [hazard ratio (HR) = 1.12, 95% CI: 0.58–2.18, P = 0.73], disease‐related (HR = 1.04, 95% CI: 0.52–2.11, P = 0.90), or HIV‐related mortality (HR = 0.93, 95% CI: 0.46–1.87, P = 0.83).ConclusionThere was no immediate benefit of the Treat All strategy on mortality, nor evidence of harm. Longer follow‐up of participants is needed to establish long‐term consequences.

Background: Since 2015, the World Health Organisation (WHO) recommends immediate initiation of antiretroviral therapy (ART) for all HIV-positive patients. Epidemiological evidence points to important health benefits of immediate ART initiation; however, the policy's economic impact remains unknown. Methods: We conducted a stepped-wedge cluster-randomised controlled trial in Eswatini to determine the causal impact of immediate ART initiation on patients' economic welfare. Fourteen healthcare facilities were non-randomly matched in pairs and then randomly allocated to transition from the standard of care (ART eligibility at CD4 counts of < 350 cells/mm3 until September 2016 and <500 cells/mm3 thereafter) to the 'Early Initiation of ART for All' (EAAA) intervention at one of seven timepoints. Patients, healthcare personnel, and outcome assessors remained unblinded. Data was collected via standardised paper-based surveys with HIV-positive, ART-naïve adults who were neither pregnant nor breastfeeding. Outcomes were patients' time use, employment status, household expenditures and household wealth. Results: A total sample of 3,019 participants were interviewed over the duration of the study. The mean number of participants approached at each facility and time step varied from 4 to 112 participants. Using mixed-effects negative binomial regressions accounting for time trends and clustering, we found no significant difference between study arms for any economic outcome. Specifically, the EAAA intervention had no significant effect on non-resting time use (RR= 1.00, [CI: 0.96, 1.05, p=0.93]) or income-generating time use (RR= 0.94, [CI: 0.73,1.20, p=0.61]). Employment and household expenditures decreased slightly but not significantly in the EAAA group, with risk ratios of 0.93 [CI: 0.82, 1.04, p=0.21] and 0.92 [CI: 0.79, 1.06, p=0.26], respectively. We also found no significant treatment effect on households' asset ownership and living standards (RR=0.96, [CI 0.92, 1.00, p=0.253]). Lastly, there was no evidence of heterogeneity in effect estimates by patients' sex, age, education, timing of HIV diagnosis and ART initiation. Conclusions: Given the neutral effect on patients' economic welfare but positive effects on health, our findings support further investments into scaling-up immediate ART for all HIV patients. Trial Registration: ClinicalTrials.gov, NCT02909218 and NCT03789448; ethical approval: Eswatini National Health Service Review Board & Harvard T.H. Chan School of Public Health Review Board.

Immediate initiation of antiretroviral therapy (ART) for all people living with HIV has important health benefits but implications for the economic aspects of patients' lives are still largely unknown. This stepped-wedge cluster-randomized controlled trial aimed to determine the causal impact of immediate ART initiation on patients’ healthcare expenditures in Eswatini. Fourteen healthcare facilities were randomly assigned to transition at one of seven time points from the standard of care (ART eligibility below a CD4 count threshold) to the immediate ART for all intervention (EAAA). 2261 patients living with HIV were interviewed over the study period to capture their past-year out-of-pocket healthcare expenditures. In mixed-effects regression models, we found a 49% decrease (RR 0.51, 95% CI 0.36, 0.72, p < 0.001) in past-year total healthcare expenditures in the EAAA group compared to the standard of care, and a 98% (RR 0.02, 95% CI 0.00, 0.02, p < 0.001) decrease in spending on private and traditional healthcare. Despite a higher frequency of HIV care visits for newly initiated ART patients, immediate ART initiation appears to have lowered patients’ healthcare expenditures because they sought less care from alternative healthcare providers. This study adds an important economic argument to the World Health Organization’s recommendation to abolish CD4-count-based eligibility thresholds for ART.

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