Same-day Versus Rapid ART Initiation in HIV-positive Individuals Presenting With Symptoms of Tuberculosis

Not Applicable

Completed

• Conditions: Human Immunodeficiency Virus (HIV) Infection
• Interventions: Other: TB results first- Therapeutic use trial; Other: ART first- Therapeutic use trial

• Registration Number: NCT05452616
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2022-07-06
• Study First Submitted QC: 2022-07-06
• Study First Posted: 2022-07-11
• Study Start: 2022-10-19
• Primary Completion: 2024-11-26
• Study Completion: 2025-01-14
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-01
• Last Update Posted: 2025-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 610

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
"TB results first" arm	TB results first- Therapeutic use trial	ART initiation only after active TB has been refuted or confirmed
"ART first" arm	ART first- Therapeutic use trial	ART initiation on the day of enrolment independent of TB investigations

Primary Outcome Measures

Name	Time	Method
HIV viral suppression <400 copies/mL	26 (22 - 40) weeks after enrolment	HIV viral suppression \<400 copies/mL (obtained from routine laboratory reports at study facility, from laboratory reports of referral facility in case of transfer out, or from dried blood spot (DBS) sample for participants without documented clinic visit but found during home visit tracing)

Secondary Outcome Measures

Name	Time	Method
Retention in care	26 (22 - 30) weeks after enrolment	Retention in care, defined as a documented ART clinic visit between 22 and 30 weeks after enrolment
Engagement in care	26 (22 - 30) weeks after enrolment	Engagement in care, defined as reporting regular ART intake, irrespective if a documented visit took place between 22 and 30 weeks after enrolment
Disengagement from care	26 (22 - 30) weeks after enrolment	Disengagement from care, defined as non-engaged in care but reached through patient tracing
Lost to follow-up	26 (22 - 30) weeks after enrolment	Lost to follow-up, defined as non-retained in care and not reached through tracing
Non-traumatic mortality	during the first 30 weeks after enrolment	Non-traumatic mortality
TB-Immune reconstitution inflammatory syndrome (IRIS)	during the first 30 weeks after enrolment	TB-Immune reconstitution inflammatory syndrome (IRIS) is defined as Adverse event of special interest (AESIs): AESIs
Serious adverse events (SAEs)	during the first 30 weeks after enrolment	SAEs
Incidence of TB disease (microbiologically confirmed and/or clinical diagnosis)	during the first 30 weeks after enrolment	Incidence of TB disease (microbiologically confirmed and/or clinical diagnosis), defined as any TB diagnosis after enrolment not classified as prevalent TB at enrolment
HIV viral suppression	at 26 (22 - 40) weeks	HIV viral suppression using different thresholds (\<20 copies/mL; \<100 copies/mL; \<1000 copies/mL)

Trial Locations

Locations (2)

SolidarMed Lesotho, Premium House #224, Kingsway, Maseru West; 🇱🇸 Maseru, Lesotho

Kamuzu University of Health Sciences, Helse Nord Tuberculosis Initiative; 🇲🇼 Blantyre, Malawi