Same-day versus rapid ART initiation in people with HIV and symptoms of tuberculosis (SaDAPT): a randomised, non-inferiority trial in Lesotho and Malawi.

BACKGROUND: Whether same-day antiretroviral therapy (ART) should be offered to people with HIV with tuberculosis symptoms or whether ART should be initiated only after tuberculosis diagnostic results are available is unknown. This randomised trial aimed to determine whether same-day ART initiation for people with tuberculosis symptoms is non-inferior to deferral until tuberculosis diagnostic results are available in achieving viral suppression at 6 months.

METHODS: We did an open-label, individually randomised, non-inferiority trial among people with HIV who were outpatients at 11 primary or secondary level health facilities in Lesotho and Malawi, were aged at least 12 years, were initiating or reinitiating ART with at least one tuberculosis symptom, and had no symptoms or signs of meningitis. Participants were randomly assigned (1:1) to be offered same-day ART or offered ART after tuberculosis was confirmed or refuted. Primary analysis was a non-inferiority comparison of viral suppression (<400 copies per mL) 26 weeks (measurement window 22-40 weeks) after enrolment, with a non-inferiority margin of 10%. The modified intention-to-treat analysis included all randomly assigned participants excluding those found ineligible after randomisation. The per-protocol analysis excluded participants who did not adhere to the randomly assigned intervention. The study is completed. The study is registered with ClinicalTrials.gov (NCT05452616).

FINDINGS: Between Oct 19, 2022, and Feb 21, 2024, 610 participants were enrolled. 590 participants were included in the modified intention-to-treat analysis of whom 356 (60%) were male, median age 37 years (IQR 31-45), median CD4 count was 202 cells per &#x3bc;L (IQR 92-374); 573 in the per-protocol analysis. 212 (71%) of 297 in the ART-first group and 199 (72%) of 276 in the tuberculosis-results-first group had viral suppression at 26 weeks in the per-protocol population (absolute risk difference -1&#xb7;6%, 95% CI -9&#xb7;1 to 6&#xb7;0) with similar results in the modified intention-to-treat population. Nine and six deaths, 11 and ten non-fatal serious adverse events, and six and five tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS) events occurred in ART-first and in tuberculosis-results-first groups, respectively.

INTERPRETATION: Same-day initiation was non-inferior to ART initiation after tuberculosis investigations regarding viral suppression and there were no indications of safety concerns or increase in IRIS. Programmatic implementation considerations and individual patient preference should guide the decision for same-day ART initiation versus initiation after receipt of tuberculosis test results for people with HIV with tuberculosis symptoms.

FUNDING: Swiss National Science Foundation.