Clinical Trials Logo

Clinical Trial 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.


Clinical Trial Description

Group 1a (n=15): 15 participants aged 2-17 years of age will have suppressed viral load and take weight-based dosing of dolutegravir once daily with two nucleoside reverse transcriptase inhibitors (NRTIs) from Days 1-28. Semi-intensive pharmacokinetic (PK) sampling for dolutegravir will be performed on Day 28. Participants start twice-daily dolutegravir and will receive once-weekly rifapentine (RPT) and isoniazid (INH) (3HP) for 12 total doses beginning on Day 29. Semi-intensive PK sampling for dolutegravir will be performed on Day 46 (3 days after the 3rd dose of HP). Additional sparse PK sampling for dolutegravir (trough concentrations (CT)) will be performed on Days 44 and 48. Semi-intensive PK sampling for RPT will be performed on day 78. PK assessments will not be performed for isoniazid given that it's a well-studied drug in children. VL will be measured at baseline (week 0) and week 7 (after 3 doses of 3HP) and week 24 (8 weeks after the last dose of 3HP). Safety labs (complete blood count (CBC), urea and electrolytes (U&E), creatinine, and liver function tests (LFT)) will be obtained at baseline (week 0), and weeks 4, 7, 12, 16, 20, and 24. Interim analysis will occur when all Group 1a participants have completed the 7-week semi-intensive PK visit (HP week 3). Enrolment into Group 2a (but not group 1b) will commence once this interim analysis is complete. Enrolment into group 1b will not be paused during this interim analysis. The interim analysis will assess PK, safety, and VL data. PK data will be modeled to assess the appropriateness of studying once-daily DTG dosing with co-administration of 3HP. The subsequent 30-45 participants age 2-17 years of age in Group 2a will receive twice or once-daily dosing of DTG, respectively, depending on PK modeling results. Group 1b (n=8 ): All participants less than 2 years of age with a suppressed viral load will take weight-based dosing of dolutegravir once daily with two nucleoside reverse transcriptase inhibitors (NRTIs) from Days 1-28. Semi-intensive PK sampling for dolutegravir will be performed on Day 28. Participants start twice-daily dolutegravir and will receive once-weekly HP for 12 total doses beginning on Day 29. Semi-intensive PK sampling for dolutegravir will be performed on Day 46 (3 days after the 3rd dose of HP). Additional sparse PK sampling for dolutegravir (trough concentrations (CT)) will be performed on Days 44 and 48. Semi-intensive PK sampling for RPT will be performed on day 78. PK assessments will not be performed for isoniazid given that it's a well-studied drug in children. VL will be measured at baseline (week 0) and weeks 7 and 24. Safety labs (complete blood count (CBC), urea and electrolytes (U&E), creatinine, and liver function tests (LFT)) will be obtained at baseline (week 0), and weeks 4, 7, 12, 16, 20 and 24. Interim analysis will occur when all Group 1b participants have completed the 7-week semi-intensive PK visit (HP week 3). Enrolment into group 2b (but not group 2a) will commence once this interim analysis is complete. Enrolment into group 2a will not be paused during this interim analysis. Interim analysis will assess PK, safety, and VL data. PK data will be modeled to assess the appropriateness of studying once-daily DTG dosing with co-administration of 3HP. The subsequent 16-24 participants in group 2b will receive twice or once-daily dosing of DTG, respectively, depending on population PK modeling results in this interim group. Group 1b may or may not occur in parallel with Group 1a. This depends on the availability of dosing and a child-friendly formulation for 3HP in children 2 years and younger. Group 2a (n=45 or 30): In the case where we proceed with evaluating once-daily DTG with 3HP in children 2-17 years of age, an additional 45 participants with suppressed viral load will be enrolled. In the case where we proceed with evaluating twice-daily DTG dosing with 3HP, an additional 30 participants with suppressed viral load will be enrolled. Both groups will take dolutegravir once daily from days 1-28 (weeks 1-4). On day 28, semi-intensive PK sampling for dolutegravir will be performed (prior to any HP dose). On day 29 (week 5), participants will either continue to take once daily DTG or their daily weight-based DTG dose will be increased to twice daily (based on group 1a data) and the first of the 12 HP weekly weight-based HP doses will be provided. Semi-intensive PK sampling for DTG will be performed on day 46 (2-4 days post third HP dose). Additional sparse PK sampling for dolutegravir (trough concentrations (CT)) will be performed on Days 44 and 48. Semi-intensive PK sampling for RPT will be performed on day 78. Viral load will be measured at baseline (screening, week 0) and at weeks 7 and 24. Safety labs (complete blood count (CBC), urea and electrolytes (U&E), and creatinine, and liver function tests (LFT)) will be obtained at baseline (screening, week 0), and weeks 4, 7, 12, 16, 20 and 24. Analysis will occur when 30 participants, in the case of twice daily DTG dosing, or 45 participants, in the case of once daily DTG dosing, have all completed the Week 24 visit. Group 2a will occur following interim results from Group 1a, but may proceed without results from Group 1b. Group 2b (n=24 or 16): In the case where we proceed with evaluating once daily DTG with 3HP in children less than 2 years of age, an additional 24 participants with suppressed viral load will be enrolled. In the case where we proceed with evaluating twice daily DTG dosing with 3HP, an additional 16 participants less than 2 years of age with suppressed viral load will be enrolled. Both groups would take dolutegravir once daily from days 1-28 (weeks 1-4). On day 28, semi-intensive PK sampling for dolutegravir will be performed (prior to any HP dose). On day 29 (week 5), participants will either continue to take once daily DTG or their daily weight-based DTG dose will be increased to twice daily (based on group 1a and group 1b data) and the first of the 12 HP weekly weight-based HP doses will be provided. Semi-intensive PK sampling for DTG will be performed on day 46 (3 days post third HP dose). Additional sparse PK sampling for dolutegravir (trough concentrations (CT)) will be performed on Days 44 and 48. Semi-intensive PK sampling for RPT will be performed on day 78. Viral load will be measured at baseline (screening, week 0) and at weeks 7 and 24. Safety labs (complete blood count (CBC), urea and electrolytes (U&E), and creatinine, and liver function tests (LFT)) will be obtained at baseline (screening, week 0), and weeks 4, 7, 12, 16, 20 and 24. Analysis will occur when 16 participants, in the case of twice-daily DTG dosing, or 24 participants, in the case of once-daily DTG dosing, have all completed the Week 24 visit. Group 2b will follow Group 1b and may or may not occur in parallel with Group 2a. This depends on the availability of dosing and a child-friendly formulation for 3HP in children 2 years and younger. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05122767
Study type Interventional
Source The Aurum Institute NPC
Contact Lisa Wolf
Phone +14433770059
Email [email protected]
Status Not yet recruiting
Phase Phase 1/Phase 2
Start date October 30, 2022
Completion date December 31, 2023

See also
  Status Clinical Trial Phase
Completed NCT03999411 - Smartphone Intervention for Smoking Cessation and Adherence to Anti-Retroviral Therapy (ART) Among People Living With Human Immunodeficiency Virus (HIV) Phase 4
Completed NCT02528773 - Efficacy of ART to Interrupt HIV Transmission Networks
Completed NCT02579135 - Reducing HIV Risk Among Adolescents: Evaluating Project HEART N/A
Active, not recruiting NCT01790373 - Evaluating a Youth-Focused Economic Empowerment Approach to HIV Treatment Adherence N/A
Completed NCT04039217 - ART Persistence in Different Body Compartments in HIV Negative MSM Phase 4
Completed NCT04124536 - Combination Partner HIV Testing Strategies for HIV-positive and HIV-negative Pregnant Women N/A
Recruiting NCT04588883 - Strengthening Families Living With HIV in Kenya N/A
Completed NCT04808609 - Smoking Cessation Pilot for People Living With HIV (PLWH) N/A
Completed NCT02758093 - Speed of Processing Training in Adults With HIV N/A
Completed NCT02500446 - Dolutegravir Impact on Residual Replication Phase 4
Recruiting NCT03805451 - Life Steps for PrEP for Youth N/A
Recruiting NCT03902431 - Translating the ABCS Into HIV Care N/A
Completed NCT00729391 - Women-Focused HIV Prevention in the Western Cape Phase 2/Phase 3
Recruiting NCT03589040 - Darunavir and Rilpivirine Interactions With Etonogestrel Contraceptive Implant Phase 2
Completed NCT03477279 - Developing and Assessing a Male Engagement Intervention in Option B+ in Malawi N/A
Completed NCT02319330 - Preventing & Treating HIV Comorbidities in India: Multi-tiered Strategy for Women N/A
Completed NCT01687218 - Safety and Acceptability Study of Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet and Rectally-Applied Tenofovir Reduced-Glycerin 1% Gel Phase 2
Recruiting NCT05084716 - Pre-Exposure Prophylaxis (PrEP) Provision for Ugandan Fisherfolk N/A
Recruiting NCT04991402 - Obesogenic Origins of Maternal and Child Metabolic Health Involving Dolutegravir
Completed NCT03483857 - Peer Navigation to Improve Engagement in Care for HIV-Positive Men Who Have Sex With Men in Ehlanzeni, South Africa N/A