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

IRB00280272

Single-arm, multi-center, Phase I/II clinical trial, in two groups. Individuals with HIV infection taking Efavirenz (EFV), nevirapine (NVP) or lopinavir/ritonavir (LPV/r) and two nucleoside reverse transcriptase inhibitors (NRTI) who have undetectable HIV viral load (VL) (\< 50 copies/mL) and an indication for tuberculosis (TB) preventive treatment (TPT), will be switched to dolutegravir (DTG) with tenofovir/emtricitabine (TDF/FTC), tenofovir/lamivudine (TDF/3TC), abacavir/lamivudine (ABC/3TC) or zidovudine/lamivudine (AZT/3TC) in accordance with South African National HIV Guidelines. Groups 1 and 2 will receive weekly HP for 12 total doses starting 4 weeks after initiating DTG. Individuals who are on an existing DTG-based plus two NRTI antiretroviral therapy (ART) regimen for at least four weeks (and have not received efavirenz, or nevirapine or lopinavir/ritonavir for at least four weeks) who have an undetectable HIV viral load may also participate.

2023-05-24

2024-12-01

2025-12-01

Recruiting

Early phase I

92

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Single-arm, multi-center, Phase I/II clinical trial, in two groups. Individuals with HIV infection taking Efavirenz (EFV), nevirapine (NVP) or lopinavir/ritonavir (LPV/r) and two nucleoside reverse transcriptase inhibitors (NRTI) who have undetectable HIV viral load (\\< 50 copies/mL) and an indication for TPT, will be switched to DTG with tenofovir/emtricitabine (TDF/FTC), tenofovir/lamivudine (TDF/3TC), abacavir/lamivudine (ABC/3TC) or zidovudine/lamivudine (AZT/3TC) in accordance with South African National HIV Guidelines. Groups 1 and 2 will receive weekly HP for 12 total doses starting 4 weeks after initiating DTG. Individuals who are on an existing DTG-based plus two NRTI ART regimen for at least four weeks (and have not received efavirenz, or nevirapine or lopinavir/ritonavir for at least four weeks) who have an undetectable HIV viral load may also participate.', 'primaryPurpose': 'OTHER', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 92, 'type': 'ESTIMATED'}}

2024-03-18