HIV Medications for Children With HIV

Not currently recruiting at 25 trial locations

Overseen By Gilead Study Team

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Gilead Sciences

Must be taking: Antiretrovirals

Disqualifiers: Drug resistance, Inadequate renal function, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safety and proper dosing of certain HIV medications in children living with HIV. Researchers will test different combinations of drugs, including atazanavir (Reyataz or ATV), cobicistat (Tybost), darunavir (Prezista or DRV), and emtricitabine/tenofovir alafenamide (Descovy, FTC/TAF), to identify the best treatment options for children. The trial is open to children who have been on stable HIV treatment for at least three months and are managing their HIV well. Participants should already be on antiretroviral therapy and have maintained control over their HIV levels. As a Phase 2, Phase 3 trial, this study evaluates the treatment's effectiveness and is in the final step before FDA approval, offering participants a chance to contribute to significant advancements in HIV care for children.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the treatments in this study have been safe in earlier research. Atazanavir, when used in children, is safe and generally well-tolerated, with manageable side effects. It usually helps control the virus effectively. Studies on cobicistat have not found any new safety issues, and the side effects align with existing knowledge.

Darunavir is another HIV medication in the trial. Previous research indicates it is safe for children aged 3 to 15 and is approved by the FDA for kids 6 and older. It is generally well-tolerated when used with other drugs like ritonavir. Additionally, studies have found emtricitabine/tenofovir alafenamide (F/TAF) to be effective and safe in children, with no serious safety issues reported over several weeks.

These findings suggest that the treatments in this clinical trial have strong safety data, making them promising options for children with HIV. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for children with HIV because they are tailored to younger patients, who often lack age-appropriate options. Unlike standard treatments that may not be suitable for infants and young children, these medications come in doses specifically adjusted for different age and weight groups, making them more accessible and potentially safer for pediatric use. Moreover, these treatments combine various antiretroviral drugs, like Atazanavir, Cobicistat, and Emtricitabine/Tenofovir Alafenamide, which might improve adherence and effectiveness by simplifying the regimen. This approach could lead to better health outcomes in children with HIV, addressing a critical gap in current HIV care.

What evidence suggests that this trial's treatments could be effective for children with HIV?

Research has shown that atazanavir, one of the treatments in this trial, effectively reduces HIV to very low levels in children's blood. Cobicistat, another treatment option, has been well tolerated and effective in children and teens when combined with other HIV medications, helping control the virus. Darunavir, also studied in this trial, strongly suppresses the virus in treatment-naive children. Emtricitabine/tenofovir alafenamide (F/TAF), included in various treatment arms, is highly effective, with some studies showing up to 100% of children achieving viral suppression, meaning the virus is kept under control. These treatments effectively maintain low HIV levels in the blood. ^{1 2 6 7 8}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9168429/

Effectiveness and Safety of Atazanavir Use for the Treatment ... Available descriptive effectiveness results showed undetectable HIV viral load (<400 or 50 copies/mL), and increased or stable CD4 cell counts ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40521667/

Pharmacokinetic data of atazanavir/ritonavir in second-line ... This nested pharmacokinetic sub-study shows that children weighing 14-24.9 kg and >25 kg taking ATV/r 200/75 mg and 300/100 mg respectively, achieve ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01335698

Phase IIIB Study Evaluating the Effects of Atazanavir ... The purpose of this study is to describe the safety, efficacy, and pharmacokinetics of a regimen of atazanavir powder boosted with ritonavir and an optimized ...

4. journals.lww.com journals.lww.com/jaids/fulltext/2025/09010/brief_report__pharmacokinetic_data_of.12.aspx

Brief Report: Pharmacokinetic Data of Atazanavir/Ritonavir... There are limited data on the pharmacokinetics of atazanavir/ritonavir (ATV/r) in children living with HIV, and no data when combined with emtricitabine/ ...

5. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/atazanavir

Pediatric Antiretroviral Drug Information - Atazanavir | NIH Safety and efficacy of atazanavir powder and ritonavir in HIV-1-infected infants and children from 3 months to <11 years of age: the PRINCE-2 study. Pediatr ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01691794

Safety Sudy of Atazanavir Boosted With Ritonavir in the ... The purpose of this study is to collect safety clinical data in HIV-infected pediatric patients aged 6 and older to younger than18 years and weighing 15 kg ...

7. fda.gov fda.gov/media/92688/download

N021567 atazanavir reissue 1 Safety and tolerability HIV-infected pediatric patients should be followed for safety for a minimum of 24 weeks at the recommended dose. In addition, please ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4355059/

The Pediatric AIDS Clinical Trials Group Protocol 1020A Use of once-daily ATV, with/without RTV, was safe and well tolerated in children, with acceptable levels of viral suppression and CD4 count increase.