HIV Clinical Trial
— DOLPHIN KIDSOfficial title:
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
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.
Status | Recruiting |
Enrollment | 92 |
Est. completion date | December 2025 |
Est. primary completion date | December 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 3 Months to 17 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
South Africa | Peri Natal HIV Research Unit - Klerksdorp Tshepong Hospital | Klerksdorp | North-West |
South Africa | The Aurum Institute: Pretoria Clinical Research Centre | Pretoria | Gauteng |
Lead Sponsor | Collaborator |
---|---|
The Aurum Institute NPC | Johns Hopkins University |
South Africa,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | PK sampling of Dolutegravir - ka parameter | Absorption rate constant (ka) in the presence or absence of once weekly HP (all groups) | PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial | |
Primary | PK sampling of Dolutegravir - Vd parameter | Volume of distribution in the presence or absence of once weekly HP (all groups) | PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial | |
Primary | PK sampling of Dolutegravir - Cl/F parameter | Oral clearance in the presence or absence of once weekly HP (all groups) | PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial | |
Primary | PK sampling of Dolutegravir - AUC parameter | Area under the plasma drug concentration-time curve in the presence or absence of once weekly HP (all groups) | PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial | |
Primary | PK sampling of Dolutegravir - Ctau parameter | Trough concentration in the presence or absence of once weekly HP (all groups) | PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial | |
Secondary | Adverse Events | Grade 3 or higher adverse events (AE) (all groups) | Adverse events to be collected from Week 1 through Week 24, to be reported throughout the trial | |
Secondary | HIV-1 RNA viral load | HIV-1 RNA viral load (copies/ml) (all groups) | HIV viral load to be measured at Screening, and Weeks 7 and 24, to be reported at end of trial | |
Secondary | PK sampling of RPT - AUC parameter | Area under curve (AUC) (all groups) | PK sampling at Week 12 (Day 78) to be reported at end of trial | |
Secondary | PK sampling of RPT - Cmax parameter | Maximum concentration (Cmax) (all groups) | PK sampling at Week 12 (Day 78) to be reported at end of trial | |
Secondary | PK sampling of RPT - Ctau parameter | Trough concentration (Ctau) (all groups) | PK sampling at Week 12 (Day 78) to be reported at end of trial | |
Secondary | DTG Dose selection | Dose options for DTG with once-weekly HP derived by simulation using nonlinear mixed effects models | Dose selection will be determined at the interim analysis to be conducted when all participants in Groups 1a and 1b have completed the Week 7 PK visit. Based upon these results, Groups 2a and 2b will receive DTG either once or twice daily. |
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