SaDAPT is a pragmatic, randomized, therapeutic-use trial comparing two approaches ("ART first" versus "TB results first") for the timing of ART initiation in PLHIV with presumptive TB, but no signs of central nervous system (CNS) disease, in a routine primary and secondary care setting in southern Africa with regard to HIV viral suppression (VL <400 copies/mL) 26 weeks after enrolment.

In this randomized controlled trial (RCT) two different, guideline-approved algorithms for antiretroviral therapy (ART) initiation in people living with HIV (PLHIV) with presumptive Tuberculosis (TB), but no signs of central nervous system (CNS) disease will be compared. In one arm, same-day initiation (SDI) of ART will be applied ("ART first") for all participants independent of the status or results of initial TB investigations. In the other arm, an approach with deferral of ART initiation until TB is excluded or confirmed and TB treatment initiated will be applied ("TB results first"). The direct comparison of the two approaches in a pragmatic, two-country RCT conducted in a representative high-prevalence setting will provide evidence on the open question of optimal timing of ART initiation in the large subgroup of PLHIV with presumptive TB outside the CNS.

Inclusion Criteria:

• 12 years or older
• HIV-positive
• Not taking ART (naïve or reported no ART intake since 90 days or more)
• Presenting with one or more TB symptoms according to W4SS
• Unknown TB status
• Planning to continue care at the study facility for at least 30 weeks
• Willing and able to consent (age 18 years or older) or assent with guardian consent (age 12 to 17 years)

Exclusion Criteria:

• Medical condition requiring admission or referral to a higher level health facility at enrolment
• Symptoms or clinical signs suggestive for diseases of the CNS
• Positive cryptococcal antigen test (CrAg)
• Reporting to be pregnant
• Taking TB treatment, TB preventive therapy (TPT) or treatment against cryptococcal meningitis

• An anonymized key dataset necessary for reproducing the primary and key secondary endpoints will be made freely available in an appropriate repository, such as zenodo.org, alongside the publication of the study results. Besides removal of variables not required for key analysis, we will remove participant identifier, study site and exact date information. Requests for access to more detailed data may be made to the corresponding author by submitting a proposal, which will be reviewed by the trial consortium.
• The statistical report for the primary and key secondary endpoints and the code to produce it will be published together with the data set.

• Within 3 months after publication of primary results

• Open access