A clinical algorithm for same-day HIV treatment initiation in settings with high TB symptom prevalence in South Africa: The SLATE II individually randomized clinical trial

Mhairi Maskew, Alana T. Brennan, Matthew P. Fox, Lungisile Vezi, Willem D. F. Venter, Peter Ehrenkranz, Sydney Rosen

Abstract

Background

Many countries encourage same-day initiation of antiretroviral therapy (ART), but evidence on eligibility for same-day initiation, how best to implement it, and its impact on outcomes remains scarce. Building on the Simplified Algorithm for Treatment Eligibility (SLATE) I trial, in which nearly half of participants were ineligible for same-day initiation mainly because of TB symptoms, the study evaluated the revised SLATE II algorithm, which allowed same-day initiation for patients with mild TB symptoms and other less serious reasons for delay.

Introduction

In its 2017 revision of the global guidelines for HIV care and treatment, the World Health Organization (WHO) called for rapid or same-day initiation of antiretroviral therapy (ART) for eligible patients testing positive for HIV [1], with the goal of reducing losses of treatment-eligible patients from care before they receive their first dose of antiretroviral (ARV) medications [2–4]. Several trials and observational studies have reported the benefits of same-day initiation, including higher rates of treatment initiation, shorter intervals between diagnosis and treatment, and ultimately larger proportions of patients achieving viral suppression among all those eligible for treatment [5–10]. In most previous studies, however, a wide range of conditions, including any symptoms of tuberculosis (TB), made patients ineligible for same-day initiation, either by excluding them from study enrollment or delaying ART initiation within the study [7,11]. The large number of patients who present at clinics with mild symptoms associated with TB, such as a cough or fever, or who are otherwise ineligible for the studies are thus generally not reflected in same-day initiation studies, and they do not qualify for same-day initiation under WHO or national guidelines.

Methods

Study design and overview

The SLATE II study, an individually randomized, nonblinded, parallel-group pragmatic evaluation, assessed the effect of the revised SLATE algorithm on ART initiation and retention in care after study enrollment. The algorithm, previously reported in [15] and illustrated in Fig 1, consisted of four screening tools, each evaluating an area of eligibility required for same-day ART initiation: (1) symptom report, (2) medical history, (3) brief physical examination, and (4) patient readiness assessment. Patients randomized to the intervention arm and deemed eligible on all four screening tools were offered initiation of ART on the same day of study enrollment, whereas those who were found to be ineligible on any one of the screens were referred back to routine care at the study site clinic for further management or investigation prior to ART initiation. Differences between the SLATE I and SLATE II algorithms are detailed in S1 Table.

Discussion

The SLATE II study successfully initiated onto ART more than 90% of nonpregnant adult patients who presented at primary healthcare clinics within 7 days and demonstrated that nearly 90% of patients are eligible for same-day ART initiation according to the SLATE II algorithm. At 8 months later, patients offered the SLATE II intervention were 26% more likely to have initiated within 28 days and then subsequently be retained in care compared with those in standard care. The intervention thus achieved improvements in both primary outcomes compared with standard care without generating any difference in known postinitiation adverse event rates.

Acknowledgments

We thank the patients who participated in the study and the staff of the study clinics for their cooperation and the City of Johannesburg and Ekurhuleni Metro in South Africa.
Citation: Maskew M, Brennan AT, Fox MP, Vezi L, Venter WDF, Ehrenkranz P, et al. (2020) A clinical algorithm for same-day HIV treatment initiation in settings with high TB symptom prevalence in South Africa: The SLATE II individually randomized clinical trial. PLoS Med 17(8): e1003226. https://doi.org/10.1371/journal.pmed.1003226

Academic Editor: Marie-Louise Newell, University of Southampton, UNITED KINGDOM

Received: March 3, 2020; Accepted: July 22, 2020; Published: August 27, 2020

Copyright: © 2020 Maskew et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Data generated by the study will be made publicly available in the Dryad repository (http://www.datadryad.org/) after the protocol has been closed (anticipated closure December 2020). Until then, data will remain under the supervision of the Boston University Medical Campus IRB and the University of the Witwatersrand Human Research Ethics Committee (HREC). Requests can be sent to the BUMC IRB at medirb@bu.edu. Data extracted from routine medical records are owned by the study sites and the South African National Department of Health and cannot be made publicly available by the authors.

Funding: Funding for the work presented here was provided by the Bill & Melinda Gates Foundation under the terms of OPP1136158 to Boston University (SR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: WDFV sits on antiretroviral initiation guideline committees both local and international, has accepted speaking honoraria from multiple manufacturers of antiretrovirals, and is on several of their advisory boards. PE is employed by the funding agency. SR is a member of the Editorial Board of PLOS Medicine. The remaining authors declare that they have no competing interests.

Abbreviations: ART, antiretroviral therapy; ARV, antiretroviral; CI, confidence interval; CONSORT, Consolidated Standards of Reporting Trials; CrAg, cryptococcal antigen; CPT, cotrimoxazole preventive therapy; CRF, case report form; IPT, isoniazid preventive therapy; IQR, interquartile range; LAM, lipoarabinomannan antigen of mycobacteria; NHLS, National Health Laboratory System; RD, risk difference; RERI, relative excess due to interaction; RR, relative risk; SLATE, Simplified Algorithm for Treatment Eligibility; TB, tuberculosis; WHO, World Health Organization.