Study of Cobicistat-Boosted Atazanavir (ATV/co), Cobicistat-Boosted Darunavir (DRV/co) and Emtricitabine/Tenofovir Alafenamide (F/TAF) in Children With HIV
Acquired Immune Deficiency Syndrome (AIDS), HIV Infections
About this trial
This is an interventional treatment trial for Acquired Immune Deficiency Syndrome (AIDS) focused on measuring Pediatrics, Adolescents, HIV, HIV-1, Treatment experienced
Eligibility Criteria
Key Inclusion Criteria:
- HIV-1 infected, virologically suppressed males and females Age ≥ 4 weeks to < 18 years (according to requirements of enrolling Cohort).
- Body weight at screening ≥ 25 to < 40 kg (Cohort 2); ≥ 14 to < 25 kg (Cohort 3); ≥ 3 to < 25 kg (Cohort 4); ≥ 3 to < 14 kg (Cohort 5)
Stable antiretroviral (ARV) regimen for a minimum of 3 months prior to the screening visit.
- Participants enrolled prior to implementation of Amendment 7: 2 NRTIs and ATV/r once daily or DRV/r once daily or twice daily.
Participants enrolled after the implementation of Amendment 9:
- Cohorts 2, 3 and 4 (Group 1): 2 NRTIs plus a third agent per local prescribing guidelines. Participants will switch from their current third agent to ATV or DRV at Day 1. Participants taking DRV must be on once-daily dosing or must switch to once daily at or prior to Day 1. Cohort 4 (Group 1), participants may also switch their current third agent to LPV/r at Day 1. Participants will switch their NRTI backbone to F/TAF.
- Cohort 4 (Groups 2 to 4) and Cohort 5 (Groups 1 to 3): 2 NRTIs plus a third agent per local prescribing guidelines or treatment naive. Participants on treatment will switch from their current third agent to ATV or LPV/r (Cohort 4 [Groups 2 to 4]), or to a third unboosted agent (Cohort 5 [Groups 1 to 3]). Participants will switch their NRTI backbone to F/TAF.
- Participants undergoing dose modifications to their ARV regimen for growth or switching medication formulations are considered to be on a stable ARV regimen.
Documented plasma HIV-1 RNA for ≥ 3 months preceding the screening visit:
Participants enrolled after the implementation of Amendment 9:
- For Cohorts 2, 3, and 4 (Group 1), virologically suppressed ≥ 3 months preceding the screening visit: HIV-1 RNA < 50 copies/mL on a stable regimen (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL)
- For Cohorts 4 (Groups 2 to 4) and Cohort 5 (Groups 1 to 3), on an ARV regimen irrespective of plasma HIV-1 RNA copies or treatment naive; a participant is considered treatment naive if ARVs were given for prevention of mother-to-child transmission but not for HIV treatment
- For virologically suppressed participants, unconfirmed virologic elevations of HIV-1 RNA ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable. If the lower limit of detection of the local HIV-1 RNA assay is < 50 copies/mL (eg, < 20 copies/mL), the plasma HIV-1 RNA level cannot exceed 50 copies/mL on 2 consecutive HIV-1 RNA tests.
Adequate renal function: Estimated Glomerular Filtration Rate (eGFR) ≥ 90 mL/min/1.73m2 using the Schwartz formula. If ≥ 1 year old, eGFR greater than or equal to the minimum normal value for age using the Schwartz Formula. If < 1 year old as follows:
- Age Minimum Value for eGFR (mL/min/1.73 m2) > 28 days to ≤ 95 days 30, ≥ 96 days to ≤ 6 months 39, > 6 to < 12 months 49
- Participants must not have documented or suspected resistance to applicable study drugs including FTC, TFV, ATV, DRV, or LPV. Participants < 14 kg (Cohorts 4 [Groups 2 to 4] and 5 [Groups 1 to 3]) with M184V/I AND HIV-1 RNA < 50 copies/mL will be allowed.
- Positive confirmatory HIV test (confirmatory nucleic acid-based testing if < 18 months of age).
- Cohort 4 (Groups 2 to 4) and Cohort 5 (Groups 1 to 3): Last dose of nevirapine or efavirenz, if applicable, ≥ 14 days prior to enrollment.
Note: Other protocol defined Inclusion/Exclusion criteria do apply.
Sites / Locations
- Pediatric Infectious Disease Associates
- Jeffrey Goodman Special Care Clinic
- Peter Morton Medical Building
- University of Colorado Denver
- The George Washington University
- University of South Florida
- Emory-Children's Center- Ponce Family and Youth Clinic
- Boston University Medical Center
- New York University School of Medicine
- SUNY Upstate Medical University
- St. Jude Children's Research Hospital
- University of Texas Health Science Center of Houston
- Hospital General de Agudos Cosme Argerich
- Fundacion Huesped
- Helios Salud
- Hospital Jose Maria Ramos Mejia
- Hopital del Nino
- University of the Free State
- University of StellenboschRecruiting
- Dr. J. Fourie Medical Practice
- King Edward VIII HospitalRecruiting
- Rahima Moosa Mother and Child HospitalRecruiting
- Be Part Yoluntu Centre
- The Aurum Institute: Pretoria Clinical Research CentreRecruiting
- Perinatal HIV Research UnitRecruiting
- HIV-NATRecruiting
- Siriraj HospitalRecruiting
- Srinagarind Hospital
- Queen Savang Vadhana Memorial Hospital
- MU-JHU Research Collaboration/MU-JHU Care Ltd
- Imperial College Healthcare NHS Trust
- University of Zimbabwe Clinical Research CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Cohort 1: Part A and Part B
Cohort 2 (Group 1)
Cohort 2 (Group 2)
Cohort 3
Cohort 4 (Group 1)
Cohort 4 (Group 2)
Cohort 4 (Group 3)
Cohort 4 (Group 4)
Cohort 5 (Group 1)
Cohort 5 (Group 2)
Cohort 5 (Group 3)
Participants ages 12 to <18 years old will receive cobicistat 150 mg with either ATV or DRV plus background regimen (BR). The BR may contain additional antiretroviral agents except for the following disallowed agents: saquinavir, indinavir, nelfinavir, double protease inhibitor (PI) regimens, raltegravir, elvitegravir, efavirenz, nevirapine, delavirdine, maraviroc, etravirine, rilpivirine, dolutegravir, and investigational antiretroviral agents.
After Protocol Amendment 9, Cohort 2 weight range will be modified to ≥ 25 to < 40 kg. Group 1 will be the current weight/age range for Cohort 2, participants aged 6 to <12 years old and ≥ 25 to < 35 kg. They will receive cobicistat (co) 150 mg and emtricitabine/tenofovir alafenamide (F/TAF) 20/25 mg with either ATV or DRV.
After Protocol Amendment 9, Cohort 2 weight range will be modified to ≥ 25 to < 40 kg. Group 2 will be the new weight range for Cohort 2, participants aged 6 to <12 years old and ≥ 35 to < 40 kg. They will receive cobicistat (co) 150 mg and emtricitabine/tenofovir alafenamide (F/TAF) 20/25 mg with DRV
Participants ages ≥ 2 years old will receive cobicistat 90 mg and F/TAF 120/15 mg with either ATV or DRV.
Participants age ≥ 4 weeks old weighing 14 to < 25 kg will receive cobicistat tablet for oral suspension (TOS) 90 mg, once daily and F/TAF TOS 120/15 mg, once daily with either ATV or DRV or lopinavir boosted by ritonavir (LPV/r). Minimum age and weight for ATV is ≥ 3 months and ≥ 5 kg, minimum age and weight for DRV is ≥ 3 years and ≥ 15 kg; participants receiving LPV/r will not receive cobicistat TOS.
Participants age ≥ 4 weeks old weighing 10 to < 14 kg will receive cobicistat TOS 30 mg (twice daily) and F/TAF TOS 60/7.5 mg, once daily with either ATV or LPV/r. Minimum age and weight for ATV is ≥ 3 months and ≥ 5 kg, respectively; participants receiving LPV/r will not receive cobicistat TOS.
Participants age ≥ 4 weeks old weighing 6 to < 10 kg will receive cobicistat TOS 30 mg (twice daily) and F/TAF TOS 30/3.75 mg, once daily with either ATV or LPV/r. Minimum age and weight for ATV is ≥ 3 months and ≥ 5 kg, respectively; participants receiving LPV/r will not receive cobicistat TOS.
Participants age ≥ 4 weeks old weighing 3 to < 6 kg will receive cobicistat TOS 30 mg (twice daily) and F/TAF TOS 15/1.88 mg, once daily with either ATV or LPV/r. Minimum age and weight for ATV is ≥ 3 months and ≥ 5 kg, respectively; participants receiving LPV/r will not receive cobicistat TOS.
Participants ages ≥ 4 weeks old weighing ≥ 10 to < 14 kg will receive F/TAF TOS 60/7.5 mg, once daily with the third unboosted drug.
Participants ages ≥ 4 weeks old weighing ≥ 6 to < 10 kg will receive F/TAF TOS 30/3.75 mg, once daily with the third unboosted drug.
Participants ages ≥ 4 weeks old weighing ≥ 3 to < 6 kg will receive F/TAF TOS 15/1.88 mg, once daily with the third unboosted drug.