Clinical trial NCT05452616: Same-day Versus Rapid ART Initiation in HIV-positive Individuals Presenting With Symptoms of Tuberculosis
Official title: Same-day Versus Rapid ART Initiation in HIV-positive Individuals Presenting With Symptoms of Tuberculosis: an Open-label Randomized Non-inferiority Trial in Lesotho and Blantyre District, Malawi
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Human Immunodeficiency Virus (HIV) Infection
Keywords: Tuberculosis (TB) infection
Acquired immunodeficiency syndrome
Antiretroviral therapy (ART)
Immune reconstitution inflammatory syndrome
People living with HIV (PLHIV)
Same-day initiation (SDI) of ART
TB preventive treatment
Sub-Saharan African countries
HIV/TB-coinfection
immune reconstitution inflammatory syndrome (IRIS)
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
name: SolidarMed
name: Kamuzu University of Health Sciences, Malawi
name: Swiss Tropical & Public Health Institute
name: Malawi-Liverpool-Wellcome Trust Clinical Research Programme
name: London School of Hygiene and Tropical Medicine
First posted: 2022-07-11
Enrollment: 610
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, parallel, open-label, 1:1 individually randomized, non-inferiority trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: HIV viral suppression <400 copies/mL
timeFrame: 26 (22 - 40) weeks after enrolment
Secondary outcomes:
measure: Retention in care
timeFrame: 26 (22 - 30) weeks after enrolment
measure: Engagement in care
timeFrame: 26 (22 - 30) weeks after enrolment
measure: Disengagement from care
timeFrame: 26 (22 - 30) weeks after enrolment
measure: Lost to follow-up
timeFrame: 26 (22 - 30) weeks after enrolment
measure: Non-traumatic mortality
timeFrame: during the first 30 weeks after enrolment
measure: Serious adverse events (SAEs)
timeFrame: during the first 30 weeks after enrolment
measure: TB-Immune reconstitution inflammatory syndrome (IRIS)
timeFrame: during the first 30 weeks after enrolment
measure: Incidence of TB disease (microbiologically confirmed and/or clinical diagnosis)
timeFrame: during the first 30 weeks after enrolment
measure: HIV viral suppression
timeFrame: at 26 (22 - 40) weeks
Other outcomes:
measure: Prevalence of active TB diagnosed at enrolment (exploratory endpoint)
timeFrame: up to a maximum of 28 days after enrolment
Locations:
city: Maseru
country: Lesotho
facility: SolidarMed Lesotho, Premium House #224, Kingsway, Maseru West
city: Blantyre
country: Malawi
facility: Kamuzu University of Health Sciences, Helse Nord Tuberculosis Initiative
Study officials:
affiliation: Division of Clinical Epidemiology, University Hospital Basel
name: Niklaus Labhardt, Prof. Dr. DTM&H, MIH
role: PRINCIPAL_INVESTIGATOR
affiliation: London School of Hygiene and Tropical Medicine
name: Rachael Mary Burke, BMBCh, MSc, DTM&H
role: PRINCIPAL_INVESTIGATOR
References: