Same-day versus rapid ART initiation in HIV-positive individuals presenting with symptoms of tuberculosis: protocol for an open-label randomized non-inferiority trial in Lesotho and Malawi

Gerber, F. et al. (2024) Same-day versus rapid ART initiation in HIV-positive individuals presenting with symptoms of tuberculosis: protocol for an open-label randomized non-inferiority trial in Lesotho and Malawi. PLoS ONE, 19(2), e0288944. (doi: 10.1371/journal.pone.0288944) (PMID:38330045) (PMCID:PMC10852279)

Abstract

Background In absence of contraindications, same-day initiation (SDI) of antiretroviral therapy (ART) is recommended for people testing HIV-positive who are ready to start treatment. Until 2021, World Health Organization (WHO) guidelines considered the presence of TB symptoms (presumptive TB) a contraindication to SDI due to the risk of TB-immune reconstitution inflammatory syndrome (TB-IRIS). To reduce TB-IRIS risk, ART initiation was recommended to be postponed until results of TB investigations were available, and TB treatment initiated if active TB was confirmed. In 2021, the WHO guidelines changed to recommending SDI even in the presence of TB symptoms without awaiting results of TB investigations based on the assumption that TB investigations often unnecessarily delay ART initiation, increasing the risk for pre-ART attrition from care, and noting that the clinical relevance of TB-IRIS outside the central nervous system remains unclear. However, this guideline change was not based on conclusive evidence, and it remains unclear whether SDI of ART or TB test results should be prioritized in people with HIV (PWH) and presumptive TB. Design and methods SaDAPT is an open-label, pragmatic, parallel, 1:1 individually randomized, non-inferiority trial comparing two strategies for the timing of ART initiation in PWH with presumptive TB (“ART first” versus “TB results first”). PWH in Lesotho and Malawi, aged 12 years and older (re)initiating ART who have at least one TB symptom (cough, fever, night sweats or weight loss) and no signs of intracranial infection are eligible. After a baseline assessment, participants in the “ART first” arm will be offered SDI of ART, while those in the “TB results first” arm will be offered ART only after active TB has been confirmed or refuted. We hypothesize that the “ART first” approach is safe and non-inferior to the “TB results first” approach with regard to HIV viral suppression (<400 copies/ml) six months after enrolment. Secondary outcomes include retention in care and adverse events consistent with TB-IRIS. Expected outcomes SaDAPT will provide evidence on the safety and effects of SDI of ART in PWH with presumptive TB in a pragmatic clinical trial setting.

• Item Type: Articles (Other)
• Additional Information: Study protocol. This study is funded through a grant of the Swiss National Science Foundation (www.snf.ch; grant number 32003B_205053) awarded to NL.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Nliwasa, Dr Marriott and Semphere, Robina Mphatso and MacPherson, Professor Peter

Creator Roles

Semphere, R. M.: Investigation, Project administration, Writing – review and editing
MacPherson, P.: Conceptualization, Methodology, Supervision, Writing – review and editing
Nliwasa, M.: Project administration, Supervision, Writing – review and editing

• Authors: Gerber, F., Semphere, R., Lukau, B., Mahlatsi, P., Mtenga, T., Lee, T., Kohler, M., Glass, T. R., Amstutz, A., Molatelle, M., MacPherson, P., Marake, N. B., Nliwasa, M., Ayakaka, I., Burke, R., and Labhardt, N.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > General Practice and Primary Care; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Copyright Holders: Copyright: © 2024 Gerber et al.
• First Published: First published in PLoS ONE 19(2): e0288944
• Publisher Policy: Reproduced under a Creative Commons licence