Additional file 1 of The socioeconomic burden of pediatric tuberculosis and role of child-sensitive social protection

Additional file 1

Subgroup analyses of the primary trial endpoint (acceptance and completion of 3HP).

Subgroup analyses of the primary trial endpoint (acceptance and completion of 3HP).</p

CONSORT 2010 checklist of information to include when reporting a randomized trial.

CONSORT 2010 checklist of information to include when reporting a randomized trial.</p

Time spent on 3HP-related activities.

BackgroundExpanding access to shorter regimens for tuberculosis (TB) prevention, such as once-weekly isoniazid and rifapentine taken for 3 months (3HP), is critical for reducing global TB burden among people living with HIV (PLHIV). Our coprimary hypotheses were that high levels of acceptance and completion of 3HP could be achieved with delivery strategies optimized to overcome well-contextualized barriers and that 3HP acceptance and completion would be highest when PLHIV were provided an informed choice between delivery strategies.Methods and findingsIn a pragmatic, single-center, 3-arm, parallel-group randomized trial, PLHIV receiving care at a large urban HIV clinic in Kampala, Uganda, were randomly assigned (1:1:1) to receive 3HP by facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between facilitated DOT and facilitated SAT using a shared decision-making aid. We assessed the primary outcome of acceptance and completion (≥11 of 12 doses of 3HP) within 16 weeks of treatment initiation using proportions with exact binomial confidence intervals (CIs). We compared proportions between arms using Fisher’s exact test (two-sided α = 0.025). Trial investigators were blinded to primary and secondary outcomes by study arm. Between July 13, 2020, and July 8, 2022, 1,656 PLHIV underwent randomization, with equal numbers allocated to each study arm. One participant was erroneously enrolled a second time and was excluded in the primary intention-to-treat analysis. Among the remaining 1,655 participants, the proportion who accepted and completed 3HP exceeded the prespecified 80% target in the DOT (0.94; 97.5% CI [0.91, 0.96] p p p ConclusionsShort-course TB preventive treatment was widely accepted by PLHIV in Uganda, and very high levels of treatment completion were achieved in a programmatic setting with delivery strategies tailored to address known barriers.Trial RegistrationClinicalTrials.govNCT03934931.</div

Trial inclusion and exclusion criteria.

BackgroundExpanding access to shorter regimens for tuberculosis (TB) prevention, such as once-weekly isoniazid and rifapentine taken for 3 months (3HP), is critical for reducing global TB burden among people living with HIV (PLHIV). Our coprimary hypotheses were that high levels of acceptance and completion of 3HP could be achieved with delivery strategies optimized to overcome well-contextualized barriers and that 3HP acceptance and completion would be highest when PLHIV were provided an informed choice between delivery strategies.Methods and findingsIn a pragmatic, single-center, 3-arm, parallel-group randomized trial, PLHIV receiving care at a large urban HIV clinic in Kampala, Uganda, were randomly assigned (1:1:1) to receive 3HP by facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between facilitated DOT and facilitated SAT using a shared decision-making aid. We assessed the primary outcome of acceptance and completion (≥11 of 12 doses of 3HP) within 16 weeks of treatment initiation using proportions with exact binomial confidence intervals (CIs). We compared proportions between arms using Fisher’s exact test (two-sided α = 0.025). Trial investigators were blinded to primary and secondary outcomes by study arm. Between July 13, 2020, and July 8, 2022, 1,656 PLHIV underwent randomization, with equal numbers allocated to each study arm. One participant was erroneously enrolled a second time and was excluded in the primary intention-to-treat analysis. Among the remaining 1,655 participants, the proportion who accepted and completed 3HP exceeded the prespecified 80% target in the DOT (0.94; 97.5% CI [0.91, 0.96] p p p ConclusionsShort-course TB preventive treatment was widely accepted by PLHIV in Uganda, and very high levels of treatment completion were achieved in a programmatic setting with delivery strategies tailored to address known barriers.Trial RegistrationClinicalTrials.govNCT03934931.</div

Participant baseline characteristics, by study arm (<i>N</i> = 1,655)^a.

Participant baseline characteristics, by study arm (N = 1,655)a.</p

3HP acceptance and completion, by study arm.

The primary outcome of 3HP acceptance and completion was defined as the proportion of participants who took at least 11 of 12 doses of 3HP within 16 weeks of treatment initiation. Secondary outcomes included 3HP acceptance, defined as the proportion of participants who took at least 1 dose of 3HP, and 3HP completion, defined as the proportion of participants who took at least 11 of 12 doses of 3HP among those who accepted (prespecified as the trial per-protocol analysis). Point estimates of proportions are represented as solid circles with corresponding 97.5% CI error bars. The dotted vertical line at 0.80 represents the prespecified acceptance and completion threshold against which we assessed our coprimary hypothesis. (*) one-sided, 98.75% CI. CI, confidence interval; DOT, directly observed therapy; SAT, self-administered therapy; 3HP, 12 weeks of once-weekly isoniazid and rifapentine.</p

Per-patient cost of facilitated 3HP delivery from the health system perspective.

Bars represent the average per-patient cost of facilitated 3HP from the health system perspective, according to individual components. “Other health system costs” include costs related to overheads, drug import fees, laboratory, office supplies, and internet charges (a, b). (a) 99DOTS is a technology whereby medications are packaged alongside toll-free phone numbers that are revealed when each dose is unpackaged, enabling patients to make toll-free calls to confirm medication dosing. Clinic staff can remotely access patient adherence data through a web dashboard. IVR reminders, check-in phone calls, and two-way messaging are also core features of the platform that enable real-time identification of patients who miss doses for further follow-up and monitoring of potential side effects. (b) Human resource costs included salaries of pharmacy technicians, lab technicians, clinicians, and entry-level and manager-level research staff. Hourly wages were calculated from government salary scales but adjusted to the project team’s structure and allocated to activities based on direct observation (time and motion studies). DOT, directly observed therapy; IVR, interactive voice response; SAT, self-administered therapy; 3HP, once-weekly isoniazid and rifapentine taken for 3 months.</p

Self-administered therapy participant pill packs.

BackgroundExpanding access to shorter regimens for tuberculosis (TB) prevention, such as once-weekly isoniazid and rifapentine taken for 3 months (3HP), is critical for reducing global TB burden among people living with HIV (PLHIV). Our coprimary hypotheses were that high levels of acceptance and completion of 3HP could be achieved with delivery strategies optimized to overcome well-contextualized barriers and that 3HP acceptance and completion would be highest when PLHIV were provided an informed choice between delivery strategies.Methods and findingsIn a pragmatic, single-center, 3-arm, parallel-group randomized trial, PLHIV receiving care at a large urban HIV clinic in Kampala, Uganda, were randomly assigned (1:1:1) to receive 3HP by facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between facilitated DOT and facilitated SAT using a shared decision-making aid. We assessed the primary outcome of acceptance and completion (≥11 of 12 doses of 3HP) within 16 weeks of treatment initiation using proportions with exact binomial confidence intervals (CIs). We compared proportions between arms using Fisher’s exact test (two-sided α = 0.025). Trial investigators were blinded to primary and secondary outcomes by study arm. Between July 13, 2020, and July 8, 2022, 1,656 PLHIV underwent randomization, with equal numbers allocated to each study arm. One participant was erroneously enrolled a second time and was excluded in the primary intention-to-treat analysis. Among the remaining 1,655 participants, the proportion who accepted and completed 3HP exceeded the prespecified 80% target in the DOT (0.94; 97.5% CI [0.91, 0.96] p p p ConclusionsShort-course TB preventive treatment was widely accepted by PLHIV in Uganda, and very high levels of treatment completion were achieved in a programmatic setting with delivery strategies tailored to address known barriers.Trial RegistrationClinicalTrials.govNCT03934931.</div

Reasons for stopping 3HP treatment.

BackgroundExpanding access to shorter regimens for tuberculosis (TB) prevention, such as once-weekly isoniazid and rifapentine taken for 3 months (3HP), is critical for reducing global TB burden among people living with HIV (PLHIV). Our coprimary hypotheses were that high levels of acceptance and completion of 3HP could be achieved with delivery strategies optimized to overcome well-contextualized barriers and that 3HP acceptance and completion would be highest when PLHIV were provided an informed choice between delivery strategies.Methods and findingsIn a pragmatic, single-center, 3-arm, parallel-group randomized trial, PLHIV receiving care at a large urban HIV clinic in Kampala, Uganda, were randomly assigned (1:1:1) to receive 3HP by facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between facilitated DOT and facilitated SAT using a shared decision-making aid. We assessed the primary outcome of acceptance and completion (≥11 of 12 doses of 3HP) within 16 weeks of treatment initiation using proportions with exact binomial confidence intervals (CIs). We compared proportions between arms using Fisher’s exact test (two-sided α = 0.025). Trial investigators were blinded to primary and secondary outcomes by study arm. Between July 13, 2020, and July 8, 2022, 1,656 PLHIV underwent randomization, with equal numbers allocated to each study arm. One participant was erroneously enrolled a second time and was excluded in the primary intention-to-treat analysis. Among the remaining 1,655 participants, the proportion who accepted and completed 3HP exceeded the prespecified 80% target in the DOT (0.94; 97.5% CI [0.91, 0.96] p p p ConclusionsShort-course TB preventive treatment was widely accepted by PLHIV in Uganda, and very high levels of treatment completion were achieved in a programmatic setting with delivery strategies tailored to address known barriers.Trial RegistrationClinicalTrials.govNCT03934931.</div