Rifapentine and Isoniazid TB Preventive Therapy (3HP) for Children Taking Dolutegravir-based Antiretroviral Treatment (DOLPHIN KIDS)

• Status: Not yet recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Aurum Institute NPC
• Collaborator: Johns Hopkins University
• Treatments: Dolutegravir

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