The Impact of WHO’s Treat All Guideline on Disease Progression Among People Enrolled in HIV Care in Central Africa: An Observational Cohort Data by Target Trial Design with Multistate Modeling

Abstract

Introduction: WHO's Treat All guidelines, which eliminate eligibility thresholds for people living with HIV to receive antiretroviral therapy, have been implemented by most countries. However, the impact of Treat All on the process of HIV disease progression is unknown.

Methods: We used a target trial design to emulate a hypothetical RCT to evaluate the policy’s impact on HIV disease progression among people living with HIV. We included people enrolled in HIV care during 2013-2019 from the Central Africa International Epidemiology Databases to Evaluate AIDS. Multistate models inferred the transitional hazards of disease progression across the four WHO clinical stages (1: asymptomatic; 2: mild; 3: advanced; 4: severe) and death. We estimated hazard ratios (HR) between a cohort enrolling in HIV care after (n=4,607) and a cohort enrolling before (n=4,439) Treat All guideline implementation, with and without covariates adjustment.

Results: Treat All implementation was associated with decreased hazards of transition in most disease stage categories,  with significant changes in transition hazards from stage 1 to stage 2  (adjusted HR (aHR) 0.64, 95% CI 0.44-0.94) and from stage 1 to death (0.37, 0.17-0.81), with no significant change in transition hazards from stage 2 to 3 (0.71, 0.50-1.01) or from stage 2 to death (0.58, 0.18-1.80).  

Conclusions: Treat All implementation substantially reduced disease progression among those with early-stage HIV disease.

Note:
Funding declaration: The project is partially supported by a pilot grant from Einstein-Rockefeller-CUNY (ERCCFAR) Center for AIDS Research. Central Africa IeDEA is supported by the National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID), the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the Fogarty International Center (FIC), the National Library of Medicine (NLM), and the Office of the Director (OD) under Award Number U01AI096299 (Central Africa-IeDEA).

Conflict of Interests: No reported conflicts.

Keywords: Treat All, HIV disease progression, Multistate model, Target trial, HIV care