Brief Summary

Tuberculosis (TB) is the world's leading infectious cause of mortality and responsible for 1/3 of deaths in people living with human immunodeficiency virus (PLHIV). Children and adolescents living with HIV (CALHIV) are disproportionately affected due to inadequate preventive services, large case detection gaps, treatment and adherence challenges, and knowledge gaps. This project will generate evidence to inform interventions targeting several of these weaknesses in the TB/HIV cascade of care. Early detection and treatment of TB improve outcomes in people living with HIV (PLHIV). A key challenge in the detection of HIV-associated TB has been the implementation of screening that identifies the correct population for diagnostic testing. Increasing evidence demonstrates the poor performance of recommended symptom screens and diagnostic approaches. Hence, the investigators aim to define a more accurate TB screening and testing strategy among PLHIV (Objective 1 and Objective 2). TB preventive treatment (TPT) averts HIV-associated TB. Nevertheless, among PLHIV, TPT initiation and completion rates are sub-optimal and effective delivery strategies are not defined. As such, the investigators aim to identify the most effective TPT delivery strategy through shared decision making and by integrating approaches proven to be effective at improving HIV treatment adherence (Objective 3). Although evidence demonstrates that isoniazid preventive therapy (IPT) is cost-effective in young children living in TB/HIV high burden settings, the cost-effectiveness of newer short-course TPT has primarily been studied in the context of a TB low-burden, high-income setting. The investigators aim to generate evidence to fill this knowledge gap and inform policy for PLHIV living in TB/HIV high burden settings (Objective 4). This study is supported by the Centers for Disease Control and Prevention of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award totaling an anticipated $5,000,000 over five years with 100 percent funded by CDC/HHS.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

6,500

participants targeted

Target at P75+ for not_applicable

Timeline

4mo left

Started Jul 2023

Typical duration for not_applicable

Geographic Reach

5 countries

5 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

3.1 years study duration

Study Progress90%

Jul 2023Sep 2026

First Submitted

Initial submission to the registry

March 3, 2022

Completed

2 months until next milestone

First Posted

Study publicly available on registry

April 22, 2022

Completed

1.2 years until next milestone

Study Start

First participant enrolled

July 11, 2023

Completed

3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2026

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2026

Last Updated

October 21, 2025

Status Verified

October 1, 2025

Enrollment Period

3.1 years

First QC Date

March 3, 2022

Last Update Submit

October 20, 2025

Conditions

Tuberculosis HIV Coinfection Tuberculosis Infection

Keywords

TB/HIV co-infectionpediatric tuberculosistuberculosis preventive therapy

Outcome Measures

Primary Outcomes (4)

TB screening
Sensitivity of C-reactive protein for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test
24-32 months
TB diagnosis
Sensitivity of Xpert Host Response Cartridge compared with the sensitivity of Xpert Ultra on sputum or on gastric aspirate using the McNemar test
24-32 months
TPT prevention outcomes
Comparing TPT completion rates in participants randomized to bi-directional messaging support vs. standard support
48 months
Cost-effectiveness
Estimating the incremental cost-effectiveness of new shortened TPT regimens measured as cost per DALYS averted for each TPT strategy and the enhanced participant support modality compared with current standard of care
32 months

Secondary Outcomes (48)

Proportion of participants selecting 3HP and the proportion selecting 6H when offered a choice within a decentralized model
48 months
Proportion of participants completing 6H and the proportion completing 3HP among participants randomized to standard support vs. bidirectional messaging
48 months
Proportion of participants initiated on TPT in the control phase vs. the intervention phase
48 months
Description of the number of participants with different TB treatment and TPT outcomes at the completion of respective therapies
48 months
Number of life years saved through novel TPT approaches
32 months
+43 more secondary outcomes

Study Arms (2)

Standard of care

NO INTERVENTION

No intervention will be administered. Observational data regarding TPT uptake and adherence will be captured on all participants presenting for care

TB screening and evaluation followed by TPT via a decentralized delivery system

EXPERIMENTAL

The intervention phase includes i) enrolling participants who have had TB disease excluded and allowing participant selection of a preferred TPT regimen, and ii) randomizing participants to one of two participant adherence support modalities.

Other: patient-centered TB preventive therapyOther: TB preventive therapy adherence support

Interventions

patient-centered TB preventive therapyOTHER

TB screening and evaluation followed by TPT via a decentralized delivery system

TB preventive therapy adherence supportOTHER

As part of this study, enhanced adherence support will be provided via bi-directional messaging and/or via clinic phone calls. All participants randomized to enhanced adherence support will receive a weekly text reminder beginning seven days after the initiation. Each message will ask participants if they would like to be contacted to discuss any questions and will prompt participants to ask questions by text if more convenient or preferable. All text-based questions from participants will be answered by a trained nurse with back up from a physician.

TB screening and evaluation followed by TPT via a decentralized delivery system

Eligibility Criteria

Sexall

Healthy VolunteersNo

Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

HIV positive or HIV exposed and presumptively positive while awaiting confirmatory testing in infants

You may not qualify if:

do not provide informed consent or assent as appropriate or are currently being treated for TB
OBJECTIVE 3:
negative TB symptom screen OR for whom TB disease has been ruled out in accordance with WHO Guidelines in adults and according to consensus definitions for child TB
do not provide informed consent or assent as appropriate or are currently being treated for TB

Contact the study team to confirm eligibility.