HIV Medications for Children With HIV

Recruiting at 24 trial locations

Overseen By Gilead Study Team

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Gilead Sciences

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

133 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical study is to learn more about the safety and dosing of study drugs, cobicistat-boosted Atazanavir (ATV/co), cobicistat-boosted darunavir (DRV/co) and emtricitabine/tenofovir alafenamide (F/TAF), in children (age ≥ 4 weeks to \< 18 years) with HIV.

Do I have to stop taking my current medications for the trial?

Yes, participants will need to switch their current third agent to a different medication as specified in the trial protocol. There is no specific washout period mentioned, but changes will occur at Day 1 of the trial.

What data supports the idea that HIV Medications for Children With HIV is an effective drug?

The available research shows that HIV medications for children, such as emtricitabine and tenofovir alafenamide, have been effective in improving the health of children with HIV. These drugs are part of combination therapies that have been shown to slow disease progression and improve survival rates. Studies have also highlighted the safety and effectiveness of these medications in children, with some showing improved safety profiles compared to older treatments. Additionally, the use of combination therapies, which include these drugs, has been recommended because they lead to better health outcomes in children with HIV. ^{1 2 3 4 5}

What safety data is available for HIV medications used in children?

The safety data for the HIV medications, specifically the combination of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide (D/C/F/TAF), shows that it is bioequivalent to the separate formulations and well-tolerated in adults and adolescents. No serious adverse events or deaths were reported in the studies. The combination has been evaluated in various trials, including the EMERALD and AMBER studies, which demonstrated its safety and efficacy in both treatment-naïve and treatment-experienced patients. Improvements in renal function and stable bone mineral density were observed, indicating better safety profiles compared to older formulations. ^{4 6 7 8 9}

Is the drug combination of Atazanavir, Cobicistat, Darunavir, and Emtricitabine/Tenofovir Alafenamide promising for children with HIV?

Yes, this drug combination is promising for children with HIV. Atazanavir is noted for its once-daily dosing and suitability for younger children. Emtricitabine and Tenofovir Alafenamide are part of a combination that has shown good antiretroviral activity and tolerability in children. These drugs are part of a combination therapy approach that has improved the quality of life and survival rates for children with HIV. ^{1 3 5 10 11}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for children aged ≥4 weeks to <18 years with HIV who weigh between ≥3 kg and <40 kg, depending on the cohort. They must have stable antiretroviral regimens for at least 3 months, adequate kidney function, and no resistance to study drugs. Children under 14 kg with certain mutations are allowed if their viral load is low.

Inclusion Criteria

My body weight fits within the specified range for a study group.

Documented plasma HIV-1 RNA for ≥ 3 months preceding the screening visit

Positive confirmatory HIV test (confirmatory nucleic acid-based testing if < 18 months of age)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cobicistat-boosted Atazanavir (ATV/co), cobicistat-boosted darunavir (DRV/co) and emtricitabine/tenofovir alafenamide (F/TAF) based on their cohort and age group

48 weeks

Regular visits as per cohort requirements

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atazanavir
• Cobicistat
• Darunavir
• Emtricitabine/Tenofovir Alafenamide

Trial Overview The study tests the safety and dosing of cobicistat-boosted Atazanavir (ATV/co), cobicistat-boosted Darunavir (DRV/co), and Emtricitabine/Tenofovir Alafenamide (F/TAF) in kids with HIV. It involves switching participants from their current treatments to these new drug combinations.

Participant Groups

Group I: Cohort 5 (Group 3) Experimental Treatment 2 Interventions

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.

Group II: Cohort 5 (Group 2) Experimental Treatment 2 Interventions

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.

Group III: Cohort 5 (Group 1) Experimental Treatment 2 Interventions

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.

Group IV: Cohort 4 (Group 4) Experimental Treatment 4 Interventions

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.

Group V: Cohort 4 (Group 3) Experimental Treatment 4 Interventions

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.

Group VI: Cohort 4 (Group 2) Experimental Treatment 4 Interventions

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.

Group VII: Cohort 4 (Group 1) Experimental Treatment 5 Interventions

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.

Group VIII: Cohort 3 Experimental Treatment 4 Interventions

Participants age ≥ 2 years old will receive cobicistat 90 mg and F/TAF 120/15 mg with either ATV or DRV.

Group IX: Cohort 2 Experimental Treatment 4 Interventions

Participants aged 6 to \<12 years old and ≥25 to \<40kg will receive cobicistat 150 mg and F/TAF 200/25 mg with either ATV or DRV.

Group X: Cohort 1: Part A and Part B Experimental Treatment 4 Interventions

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.

Atazanavir is already approved in United States, European Union for the following indications:

Approved in United States as Reyataz for:

• HIV-1 infection

Approved in European Union as Reyataz for:

• HIV-1 infection

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Findings from Research

The development of antiretroviral therapy has greatly improved the health outcomes for children with HIV, with 21 FDA-approved agents available, though only a few are suitable for those under 18.

Among the 7 newer antiretroviral agents approved since 2000, only 3 are currently approved for pediatric use, but studies are ongoing to evaluate the safety and efficacy of the others in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Antiretroviral Therapies for Pediatric HIV Infection. Morris, JL., Kraus, DM.[2021]

In a study involving 23 virologically suppressed HIV-infected children aged 6-11 years, the fixed-dose combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide was found to be effective and well tolerated, with all participants maintaining viral suppression after 24 weeks.

The pharmacokinetic profiles showed higher exposure levels of the drug components compared to adults, but there were no serious adverse events, indicating a favorable safety profile for this regimen in children weighing at least 25 kg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and pharmacokinetics of single-tablet elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in virologically suppressed, HIV-infected children: a single-arm, open-label trial. Natukunda, E., Gaur, AH., Kosalaraksa, P., et al.[2019]

Combination antiretroviral therapy has significantly improved the prognosis and quality of life for both adults and children with HIV, utilizing at least three drugs from different classes to enhance treatment effectiveness.

Despite the availability of 21 antiretroviral agents, only 11 are approved for children under 6, highlighting ongoing challenges in treatment adherence, tolerability, and the need for new agents that can combat drug-resistant HIV strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New antiretroviral drugs in clinical use. Chearskul, P., Rongkavilit, C., Al-Tatari, H., et al.[2022]

The study of 50 treatment-naive adolescents with HIV showed that the single-tablet regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide was well tolerated over 48 weeks, with no discontinuations due to adverse events.

Pharmacokinetic parameters for the regimen were similar to those observed in adults, indicating that this treatment could be effective and safe for adolescents, supporting further research in younger children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and pharmacokinetics of a single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in treatment-naive, HIV-infected adolescents: a single-arm, open-label trial. Gaur, AH., Kizito, H., Prasitsueubsai, W., et al.[2021]

In a study of 74 HIV-1-infected children and adolescents treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) for at least 6 months, 37.8% experienced virological failure, particularly those with poor viral suppression at baseline, highlighting the importance of monitoring treatment adherence.

BIC/FTC/TAF demonstrated a high genetic barrier to resistance, with only one case of a mutation observed, suggesting it is a promising treatment option for pediatric patients who may struggle with adherence and virological control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bictegravir/emtricitabine/tenofovir alafenamide in paediatrics: Real-life experience from a French cohort (2019-2023). Frange, P., Veber, F., Burgard, M., et al.[2023]

The study demonstrated that the pediatric fixed-dose combination of D/C/F/TAF (675/150/200/10 mg) is bioequivalent to the separate commercially available formulations, indicating it can effectively deliver the same therapeutic benefits for HIV-1 treatment.

No serious adverse events or significant safety concerns were reported during the study, suggesting that the new formulation is safe for use in healthy adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence of a Pediatric Fixed-Dose Combination Tablet Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Compared With Coadministration of the Separate Agents in Healthy Adults: An Open-Label, Randomized, Replicate Crossover Study. Van Hemelryck, S., Van Landuyt, E., Ariyawansa, J., et al.[2023]

In a phase 3 study involving 1141 treatment-experienced, virologically suppressed adults, switching to the single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) showed similar virologic rebound rates (2.5%) compared to the control group (2.1%), indicating its efficacy across various patient subgroups.

The D/C/F/TAF regimen was found to be safe with low adverse event rates and demonstrated improvements in renal and bone health parameters, making it a favorable option for patients regardless of their demographic characteristics or prior treatment history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-experienced, virologically suppressed patients with HIV-1: subgroup analyses of the phase 3 EMERALD study. Huhn, GD., Eron, JJ., Girard, PM., et al.[2021]

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) showed high virologic response rates at Week 96, with 85% in treatment-naïve adults and 91% in treatment-experienced adults, indicating its efficacy in managing HIV.

The treatment demonstrated a low rate of virologic failure (6% in AMBER and 1% in EMERALD) and no resistance mutations were observed, highlighting its strong barrier to resistance and safety profile regarding bone and renal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Week 96 subgroup analyses of the phase 3, randomized AMBER and EMERALD trials evaluating the efficacy and safety of the once daily darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) single-tablet regimen in antiretroviral treatment (ART)-naïve and -experienced, virologically-suppressed adults living with HIV-1. Huhn, GD., Wilkin, A., Mussini, C., et al.[2022]

In the phase 3 AMBER study involving 725 treatment-naïve adults, the single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) demonstrated a virologic response rate of 91%, comparable to 88% for the control group, indicating its efficacy across various patient subgroups.

The safety profile of D/C/F/TAF was similar to the control, with improvements in kidney function and stable bone mineral density observed, suggesting it is a well-tolerated treatment option for diverse demographic and clinical characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naïve patients with HIV-1: subgroup analyses of the phase 3 AMBER study. Rashbaum, B., Spinner, CD., McDonald, C., et al.[2021]

E/C/FTC/TAF, a combination antiretroviral therapy, is well tolerated and shows effective antiviral activity in children and adolescents with HIV-1, but more research is needed to fully establish its safety and efficacy in this population.

Currently, three integrase inhibitors are approved for use in children, with E/C/FTC/TAF being suitable for those aged 6 years and older, highlighting the need for pediatric formulations to optimize HIV treatment in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of elvitegravir plus cobicistat plus tenofovir alafenamide plus emtricitabine as a single-tablet regimen for the treatment of HIV in children and adolescents. Giacomet, V., Cossu, MV., Capetti, AF., et al.[2021]

In a study involving 195 HIV-infected children, atazanavir (ATV) treatment resulted in significant viral suppression, with 60.4% of participants achieving HIV RNA levels ≤ 400 copies/mL at week 24 and 58.5% at week 48.

The treatment was generally safe, with the most common adverse effect being increased bilirubin levels, affecting 9% of subjects, while overall, ATV was well tolerated and led to a median increase of 196.5 CD4 cells/mm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of atazanavir-based therapy in HIV-infected infants, children and adolescents: the Pediatric AIDS Clinical Trials Group Protocol 1020A. Rutstein, RM., Samson, P., Fenton, T., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

New Antiretroviral Therapies for Pediatric HIV Infection. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and pharmacokinetics of single-tablet elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in virologically suppressed, HIV-infected children: a single-arm, open-label trial. [2019]

3. India pubmed.ncbi.nlm.nih.gov

New antiretroviral drugs in clinical use. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and pharmacokinetics of a single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in treatment-naive, HIV-infected adolescents: a single-arm, open-label trial. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Bictegravir/emtricitabine/tenofovir alafenamide in paediatrics: Real-life experience from a French cohort (2019-2023). [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Bioequivalence of a Pediatric Fixed-Dose Combination Tablet Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Compared With Coadministration of the Separate Agents in Healthy Adults: An Open-Label, Randomized, Replicate Crossover Study. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-experienced, virologically suppressed patients with HIV-1: subgroup analyses of the phase 3 EMERALD study. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Week 96 subgroup analyses of the phase 3, randomized AMBER and EMERALD trials evaluating the efficacy and safety of the once daily darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) single-tablet regimen in antiretroviral treatment (ART)-naïve and -experienced, virologically-suppressed adults living with HIV-1. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naïve patients with HIV-1: subgroup analyses of the phase 3 AMBER study. [2021]

10. England pubmed.ncbi.nlm.nih.gov

An evaluation of elvitegravir plus cobicistat plus tenofovir alafenamide plus emtricitabine as a single-tablet regimen for the treatment of HIV in children and adolescents. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of atazanavir-based therapy in HIV-infected infants, children and adolescents: the Pediatric AIDS Clinical Trials Group Protocol 1020A. [2021]