Mortality under early access to antiretroviral therapy vs. Eswatini’s national standard of care: the MaxART clustered randomized stepped‐wedge trial

Objectives Current 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. Methods MaxART 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%). Results Between 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). Conclusion There 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.