Preventing tuberculosis in children with HIV using rifapentine and isoniazid
Safety, Tolerability and Drug-drug Interactions of Short-course Treatment of Latent Tuberculosis Infection With High-dose Once-weekly Rifapentine and Isoniazid (3HP) Among Infants, Children and Adolescents Living With HIV Taking Dolutegravir-based Antiretroviral Treatment
This study is testing a combination of two medications, rifapentine and isoniazid, to see if they can help prevent tuberculosis in children with HIV who are already on treatment.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 92 (estimated) |
| Ages | 3 Months to 17 Years |
| Sex | All |
| Sponsor | The Aurum Institute NPC Academic / other |
| Locations | 2 sites (Pretoria, Gauteng and 1 other locations) |
| Trial ID | NCT05122767 on ClinicalTrials.gov |
What this trial studies
This clinical trial evaluates the effectiveness of a preventive therapy combining rifapentine and isoniazid (3HP) in children aged 3 months to 17 years who are living with HIV and on dolutegravir-based antiretroviral treatment. Participants will receive weight-based dosing of dolutegravir along with the preventive therapy after achieving an undetectable viral load. The study includes pharmacokinetic assessments to monitor drug levels and safety evaluations throughout the treatment period. The trial aims to determine the safety and efficacy of this regimen in preventing tuberculosis in this vulnerable population.
Who should consider this trial
Good fit: Ideal candidates are children aged 3 months to 17 years with documented HIV infection and an undetectable viral load.
Not a fit: Patients with confirmed or suspected active tuberculosis or those who have recently completed tuberculosis treatment may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could significantly reduce the incidence of tuberculosis in children living with HIV.
How similar studies have performed: Previous studies have shown success with similar preventive therapies in adults, but this specific approach in children is novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion criteria include: * Age 3 months through 17 years * Weight \> 3 kg * Documented HIV infection by DNA polymerase chain reaction (PCR) or plasma RNA-PCR if \<18 months and by HIV-ELISA if 18 months and confirmed with a DNA PCR or RNA-PCR from an independent sample * Undetectable HIV-1 viral load Exclusion criteria * Confirmed or suspected TB disease (evidenced by symptoms and/or clinical exam findings and/or chest radiographic findings suggestive of TB, positive mycobacterial culture or molecular TB testing, or currently on TB treatment for active TB disease) * Likely to move from the study area during the study period * Known exposure to TB cases with known or suspected resistance to isoniazid or rifampicin in the source case * TB treatment within the past year * Prior completion of a TPT course without re-exposure to persons with infectious TB since TPT completion * Receipt of once-daily INH for \>30 days that was given for at least 14 consecutive days in the 30 days prior to enrolment. * Sensitivity or intolerance to dolutegravir, isoniazid, or rifamycins * Suspected acute hepatitis or known chronic or unstable liver disease\^; HBsAg positivity or anti-hepatitis A virus (HAV) Immunoglobulin M (IgM) antibody; any infant born to a Hepatitis C positive mother in whom in utero infection in the infant is unknown or under evaluation * alanine aminotransferase (ALT) \> 3 times the upper limit of normal (ULN) * Total bilirubin \> 2 .5 times the ULN * Absolute neutrophil count (ANC) ≤ 750 cells/mm3 * Estimated creatinine clearance \< 60 ml/min (Bedside Schwartz formula)\* * Pregnancy or breastfeeding (infant of a breastfeeding mother is allowed) * Women of childbearing potential who are unable or unwilling to use two forms of contraception\*\* * Weight for age Z score below 2 or severe clinical malnutrition * On prohibited medications e.g. dofetilide (see Appendix 1) * Known porphyria
Where this trial is running
Pretoria, Gauteng and 1 other locations
- The Aurum Institute: Pretoria Clinical Research Centre — Pretoria, Gauteng, South Africa (Recruiting)
- Peri Natal HIV Research Unit - Klerksdorp Tshepong Hospital — Klerksdorp, North-West, South Africa (Recruiting)
Study contacts
- Principal investigator: Nicole Salazar-Austin — JHU SOM Ped Infectious Disease
- Study coordinator: Jayajothi Moodley
- Email: JMoodley@auruminstitute.org
- Phone: +27826593766
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.