Children exposed to TB are often at risk of developing active TB disease which can be severe or widespread in absence of TB preventive treatment (TPT). Prevention of TB in children through TPT is an important strategy to reduce the burden of TB disease in children. This strategy has been used been shown to reduce mortality among HIV positive adults and has been recommended by WHO for adults and children living with HIV in high burden TB settings. WHO currently recommends Rifapentin in combination with INH once weekly for 12 weeks (3HP regimen) for children aged less than 13 years of age.

This study purposes to establish the appropriate dose for Rifapentine combined with Isoniazid taken daily for 28 days (1HP regimen) using the child-friendly formulation of RPT that is dispersible in water and to obtain safety data and high-quality PK data for HIV negative children less than 13 years of age and HIV positive children aged 12 weeks to less than 13 years on  DTG as part of their ART. The study will have PK visits during which participants will take study medication under observation at the clinic followed by blood draws at 4 time points within 8 hours to measure drug levels.

Young children have a high risk of developing active tuberculosis (TB) disease, including severe and disseminated forms of TB, following infection with Mycobacterium tuberculosis (M.tb), in the absence of TB preventive treatment (TPT). Human immunodeficiency virus (HIV) infection and HIV exposure without infection put children at even higher risk of progression to TB disease (2-4).

Prevention of TB in children through post-exposure TPT is an important public health strategy to reduce the burden of TB disease among children. In clinical trials, TPT has been shown to reduce mortality among adults living with HIV by 33%, independent of antiretrovirals (ARVs), and has been recommended by the World Health Organization (WHO) for adults and children living with HIV in high-burden TB settings since 1997. TPT is also highly effective in treating latent TB infection (LTBI) and is a key strategy for reducing TB incidence and meeting the WHO END TB Strategy.

The purpose of this study is to determine the appropriate dose for 1HP using the child-friendly formulation of RPT that is dispersible in water and to obtain safety data and high-quality PK data for children less than 13 years of age. To determine the weight-band dosing of RPT taken as part of the 1HP regimen by evaluating:  PK RPT exposures among children with and without HIV .The study will also assess the Safety and tolerability of the 1HP regimen among children with HIV while receiving twice-daily DTG and children without HIV through 28 days of dosing  and evaluate the effect of RPT taken as part of the 1HP regimen on the PK of DTG (Cohort 2 only).Cohort 1 participants will be HIV negative children less than from birth to less than 13 years while Cohort 2 participants will be HIV positive children age 12 weeks to less than 13 years of age on a DTG containing regimen.

The study will enroll up to 144 participants globally of which Kericho site anticipates enrolling 30. The site will screen 45 participants to enroll 30 participants. Participants will be in the study for 6 months during which they will have 6 study visits.