Regression discontinuity analysis demonstrated varied effect of Treat-All on CD4 testing among Southern African countries

Elizabeth Zaniewski,Ellen Brazier,Cam Ha Dao Ostinelli,Robin Wood,Meg Osler,Karl-Günter Technau,Joep J Van Oosterhout,Nicola Maxwell,Janneke Van Dijk,Hans Prozesky,Matthew P Fox,Jacob Bor,Denis Nash,Matthias Egger

doi:10.1016/j.jclinepi.2021.09.001

Abstract

ObjectiveTo determine whether Treat-All policy impacted laboratory testing practices of antiretroviral therapy (ART) programs in Southern Africa. Study Design and SettingWe used HIV cohort data from Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in a regression discontinuity design to estimate changes in pre-ART CD4 testing and viral load monitoring following national Treat-all adoption that occurred during 2016 to 2017. This study included more than 230,000 ART-naïve people living with HIV (PLHIV) aged five years or older who started ART within two years of national Treat-All adoption. ResultsWe found pre-ART CD4 testing decreased following adoption of Treat-All recommendations in Malawi (-21.4 percentage points (pp), 95% confidence interval, CI: -26.8, -16.0) and in Mozambique (-8.8pp, 95% CI: -14.9, -2.8), but increased in Zambia (+2.7pp, 95% CI: +0.4, +5.1). Treat-All policy had no effect on viral load monitoring, except among females in South Africa (+7.1pp, 95% CI: +1.1, +13.0). ConclusionTreat-All policy expanded ART eligibility, but led to reductions in pre-ART CD4 testing in some countries that may weaken advanced HIV disease management. Continued and expanded support of CD4 and viral load laboratory capacity is needed to further improve treatment successes and allow for uniform evaluation of ART implementation across Southern Africa.

Highlights

In 2015 the World Health Organization (WHO) released "Treat-All" guidelines recommending immediate antiretroviral therapy (ART) for all people living with HIV (PLHIV) regardless of CD4 cell count [1]
A recent global International epidemiology Databases to Evaluate AIDS (IeDEA) study found Treat-All adoption in low or lower-middle income countries led to an immediate decline in pre-ART CD4 testing among adults who enrolled in HIV care after Treat-All adoption [12], we found considerable heterogeneity in the direction and magnitude of the immediate effect in such countries [33], which varied by sex
We found Treat-All led to heterogeneous changes in pre-ART CD4 testing, there was no evidence of an immediate effect on viral load monitoring, aside from a moderate increase among women in South Africa, suggesting viral load testing volume increased proportional to the number newly starting treatment

Summary

Introduction

In 2015 the World Health Organization (WHO) released "Treat-All" guidelines recommending immediate antiretroviral therapy (ART) for all people living with HIV (PLHIV) regardless of CD4 cell count [1]. The guidelines, progressively adopted by countries, removed CD4 eligibilitiy thresholds for initiating ART, but still recommend CD4 testing to identify PLHIV with advanced HIV disease who could benefit from prophylactic and diagnostic interventions prior to starting or restarting ART [2,3,4]. Guidelines recommend viral load testing six months after initiating or switching ART to assess HIV-1 viral suppression [2]. An unsuppressed viral load may indicate treatment failure and prompts interventions to improve treatment outcome [2,5,6]. CD4 and viral load testing are crucial population-level indicators of progress towards public health goals [4,7,8,9].

Methods

Discussion

Conclusion