Study to Evaluate the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents and Virologically Suppressed Children

NCT ID: NCT01854775

Last Updated: 2026-01-09

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

129 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-06

Study Completion Date

2025-06-18

Brief Summary

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The primary objectives of Cohort 1 are to evaluate the steady state pharmacokinetics (PK) for elvitegravir (EVG) and tenofovir alafenamide (TAF) and confirm the dose of the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) STR (Part A) and to evaluate the safety and tolerability of E/C/F/TAF STR through Week 24 (Part B) in human immunodeficiency virus - 1 (HIV-1) infected, antiretroviral (ARV) treatment-naive adolescents.

The primary objectives of Cohort 2 are to evaluate the PK of EVG and TAF (Part A), and to evaluate the safety and tolerability of E/C/F/TAF through Week 24 (Part B) in virologically suppressed HIV-1 infection children 6 to \< 12 years weighing \>= 25 kg.

The primary objectives of Cohort 3 are to evaluate the PK of EVG and TAF and confirm the dose of the STR, and to evaluate the safety and tolerability of E/C/F/TAF low dose (LD) STR in virologically suppressed HIV-1 infected children ≥ 2 years of age and weighing ≥ 14 to \< 25 kg.

Detailed Description

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Conditions

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Acquired Immune Deficiency Syndrome (AIDS) HIV Infections

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1: Age 12 to < 18 Years and Weight ≥ 35 kg

Treatment naive adolescents (12 to \< 18 years of age) living with human immunodeficiency virus (HIV) will receive E/C/F/TAF (150/150/200/10 mg) fixed-dose combination (FDC) once daily for 48 weeks. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF become commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country.

Group Type EXPERIMENTAL

E/C/F/TAF

Intervention Type DRUG

Tablets administered orally with food.

Cohort 2: Age 6 to < 12 Years and Weight ≥ 25 kg

Children (6 to \< 12 years of age weighing ≥ 25 kg) with HIV who were virologically suppressed will receive E/C/F/TAF (150/150/200/10 mg) FDC once daily for 48 weeks. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF become commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country.

Group Type EXPERIMENTAL

E/C/F/TAF

Intervention Type DRUG

Tablets administered orally with food.

Cohort 3: Age ≥2 Years and Weight ≥ 14 to <25 kg

Children (≥ 2 years of age weighing ≥ 14 to \< 25 kg) with HIV who were virologically suppressed will receive E/C/F/TAF (90/90/120/6 mg) FDC once daily for 48 weeks. Participants who attain a weight of ≥ 25 kg during the course of the study will switch to adult E/C/F/TAF (150/150/200/10 mg) tablets administered orally, once daily with food. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF became commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country.

Group Type EXPERIMENTAL

E/C/F/TAF

Intervention Type DRUG

Tablets administered orally with food.

E/C/F/TAF (Low Dose)

Intervention Type DRUG

90/90/120/6 mg STR administered once daily orally with food.

Interventions

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E/C/F/TAF

Tablets administered orally with food.

Intervention Type DRUG

E/C/F/TAF (Low Dose)

90/90/120/6 mg STR administered once daily orally with food.

Intervention Type DRUG

Other Intervention Names

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Genvoya®

Eligibility Criteria

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Inclusion Criteria

* Cohort 1

* Age at baseline: 12 years to \< 18 years old
* Weight at screening: ≥ 35 kg (77 lbs)
* Plasma HIV-1 ribonucleic acid (RNA) levels of ≥ 1,000 copies/mL at screening (Roche COBAS TaqMan v2.0)
* Screening genotype report shows sensitivity to EVG, emtricitabine (FTC) and tenofovir (TFV)
* No prior use of any approved or experimental anti-HIV-1 drug for any length of time
* Cohort 2

* Age at baseline: 6 years to \< 12 years old
* Weight at screening: ≥ 25 kg (55 lbs)
* Plasma HIV-1 RNA of \< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is \> 50 copies/mL) for ≥ 180 consecutive days (6 months) prior to screening on a stable antiretroviral regimen, without documented history of resistance to any component of E/C/F/TAF STR.
* Cohort 3

* Age at baseline: ≥ 2 years old
* Weight at screening: ≥ 14 kg (31 lbs) to \< 25 kg (55 lbs)
* Plasma HIV-1 RNA: \< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is \> 50 copies/mL) for ≥ 180 consecutive days (6 months) prior to screening on a stable antiretroviral regimen, without prior history of resistance to any component of E/C/F/TAF STR

Exclusion Criteria

* Hepatitis B or hepatitis C virus infection
* Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the screening visit.
* Individuals experiencing decompensated cirrhosis
* Pregnant or lactating females
Minimum Eligible Age

2 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Miller's Children Hospital

Long Beach, California, United States

Site Status

Children's Research Institute

Washington D.C., District of Columbia, United States

Site Status

Emory University School of Medicine

Atlanta, Georgia, United States

Site Status

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

KIDCRU Ward J8

Cape Town, , South Africa

Site Status

Be Part Yoluntu Centre

Cape Town, , South Africa

Site Status

Desmond Tutu HIV Foundation

Cape Town, , South Africa

Site Status

Perinatal HIV Research Unit Baragwanath Hospital

Johannesburg, , South Africa

Site Status

Clinical HIV Research Unit

Johannesburg, , South Africa

Site Status

Empilweni Services and Research Unit (ESRU)

Johannesburg, , South Africa

Site Status

The HIV Netherlands Australia Thailand Research collaboration (HIV-NAT)

Bangkok, , Thailand

Site Status

Queen Savang Vadhana Memorial Hospital

Chon Buri, , Thailand

Site Status

Department of Pediatrics, Faculty of Medicine, Khon Kaen University

Khon Kaen, , Thailand

Site Status

Joint Clinical Research Centre

Kampala, , Uganda

Site Status

University of Zimbabwe - Clinical Research Centre

Belgravia, , Zimbabwe

Site Status

Countries

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United States South Africa Thailand Uganda Zimbabwe

References

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Rakhmanina N, Gaur A, Natukunda E, Chokephaibulkit K, Liberty A, Kido A, et al. Acceptability and palatability of the single-tablet regimens of B/F/TAF and E/C/F/TAF in children (6-12 years) living with HIV infection [Abstract 33]. 10th International Workshop on HIV Pediatrics; 2018 July 21-22; Amsterdam, The Netherlands

Reference Type RESULT

Sharma S, Gupta S, Majeed S, Strehlau R, Hellstrom E, Liu Y, et al. Exposure-Safety of Tenofovir in Pediatric HIV-Infected Participants: Comparison of Tenofovir Alafenamide & Tenofovir Disoproxil Fumarate [Abstract 23]. 10th International Workshop on HIV Pediatrics; 2018 July 21-22; Amsterdam, The Netherlands.

Reference Type RESULT

Natukunda E, Gaur AH, Kosalaraksa P, Batra J, Rakhmanina N, Porter D, Shao Y, Zhang H, Pikora C, Rhee MS. 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. Lancet Child Adolesc Health. 2017 Sep;1(1):27-34. doi: 10.1016/S2352-4642(17)30009-3. Epub 2017 Jun 29.

Reference Type RESULT
PMID: 30169223 (View on PubMed)

Rakhmanina N, Natukunda E, Kosalaraksa P, Batra J, Gaur A, Shao Y, et al. Safety and efficacy of E/C/F/TAF in virologically suppressed, HIV-infected children through 48 weeks [Abstract 32]. 9th International Workshop on HIV Pediatrics; 2017 July 21-22; Paris, France.

Reference Type RESULT

Gaur A, Natukunda E, Kosalarksa P, Batra J, Rakhmanina N, Coluci A, et al. Pharmacokinetics, Safety, and Efficacy of E/C/F/TAF in HIV-1-Infected Children (6 to <12 years) [Poster 424]. Conference on Retroviruses and Opportunistic Infections (CROI); 2017 February 13-16; Seattle Washington.

Reference Type RESULT

Gaur AH, Kizito H, Prasitsueubsai W, Rakhmanina N, Rassool M, Chakraborty R, Batra J, Kosalaraksa P, Luesomboon W, Porter D, Shao Y, Myers M, Ting L, SenGupta D, Quirk E, Rhee MS. 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. Lancet HIV. 2016 Dec;3(12):e561-e568. doi: 10.1016/S2352-3018(16)30121-7. Epub 2016 Oct 17.

Reference Type RESULT
PMID: 27765666 (View on PubMed)

Gaur A, Kizito H, Chakraborty R, Batra J, Kosalaraksa P, Luesomboon W, et al. Safety and Efficacy of E/C/F/TAF in HIV-1 Infected Treatment-Naive Adolescents [Poster 817]. Conference on Retroviruses and Opportunistic Infections (CROI); 2016 February 22-25; Boston, Massachusetts.

Reference Type RESULT

Natukunda E, Liberty A, Strehlau R, Hellstrom E, Hakim JG, Kaur H, et al. Safety, pharmacokinetics and efficacy of low dose E/C/F/TAF in virologically suppressed children ≥ 2 years old living with HIV. (Abstract OABLB0101) 23rd International AIDS Conference; 06-10 July 2020 (Virtual).

Reference Type RESULT

Natukunda E, Liberty A, Strehlau R, Hellstrom E, Hakim J, Kaur H, et al. Safety, pharmacokinetics, and efficacy of low dose E/C/F/TAF in virologically suppressed children ≥ 2 years old living with HIV. (Abstract 3) International Workshop on HIV Pediatrics 2020; 16-17 November 2020 (Virtual).

Reference Type RESULT

Liberty A, Strehlau R, Rakhmanina N, Chokephaibulkit K, Koziara J, Kaur H, et al. Acceptability and palatability of low dose B/F/TAF and E/C/F/TAF in children (≥ 2y) with HIV. (Abstract 57) International Workshop on HIV Pediatrics 2020; 16-17 November 2020 (Virtual).

Reference Type RESULT

Kizito H, Gaur A, Prasitsuebsai W, Rakhmanina N, Lawson E, Shao Y, et al. Safety, Efficacy and Pharmacokinetics of the Integrase Inhibitor-Based E/C/F/TAF Single-Tablet Regimen in Treatment-Naïve HIV-Infected Adolescents Through 24 Weeks of Treatment [Poster 953]. Conference on Retroviruses and Opportunistic Infections; 2015 February 23-26; Seattle, WA.

Reference Type RESULT

Porter DP, Bennett SR, Quirk E, Miller MD, White KL. Lack of Emergent Resistance in HIV-1-Infected Adolescents on Elvitegravir-Based STRs [Poster 952]. Conference on Retroviruses and Opportunistic Infections (CROI); 2015 23-26 February; Seattle, WA.

Reference Type RESULT

Kizito H, Gaur A, Prasitsuebsai W, Rakhmanina N, Lawson E, Shao Y, et al. Safety, Efficacy and Pharmacokinetics of the Integrase Inhibitor-Based E/C/F/TAF Single-Tablet Regimen in Treatment-Naïve HIV-Infected Adolescents Through 24 Weeks of Treatment [Poster 36]. 16th International Workshop on Clinical Pharmacology of HIV & Hepatitis Therapy; 2015 26-28 May; Washington, DC.

Reference Type RESULT

Kizito H, Gaur A, Prasitsuebsai W, Rakhmanina N, Chokephaibulkit K, Fourie J, et al. Changes in renal laboratory markers and bone mineral density in treatment-naïve HIV-1-infected adolescents initiating INSTI-based single-tablet regimens containing tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) [Presentation #MOAB0104]. International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention; 2015 19-22 July; Vancouver, Canada.

Reference Type RESULT

Natukunda E, Gaur AH, Kosalaraksa P, Hellstrom E, Strehlau R, Liberty A, Cox S, Leisegang R, Palaparthy R, Crowe S, Vieira V, Kersey K, Rakhmanina N. Pharmacokinetics, safety and efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in children with HIV aged from 2 years and weighing at least 14 kg. J Int AIDS Soc. 2025 Feb;28(2):e26414. doi: 10.1002/jia2.26414.

Reference Type RESULT
PMID: 39888251 (View on PubMed)

Natukunda E, Gaur AH, Deville JG, Kosalaraksa P, Strehlau R, Castano E, Liberty A, Crowe S, Palaparthy R, Vieira VA, Kersey K, Rakhmanina N, Gordon CM. Longitudinal Evaluation of Bone Safety in Children and Adolescents With HIV-1 Starting Tenofovir Alafenamide-Containing Antiretroviral Therapy. J Pediatric Infect Dis Soc. 2025 Aug 7;14(7):piaf062. doi: 10.1093/jpids/piaf062.

Reference Type RESULT
PMID: 40632108 (View on PubMed)

Provided Documents

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Document Type: Study Protocol: Protocol Amendment 6

View Document

Document Type: Study Protocol: Protocol Amendment 7

View Document

Document Type: Statistical Analysis Plan: Interim 4 Analysis

View Document

Document Type: Statistical Analysis Plan: Interim 6 Analysis

View Document

Document Type: Statistical Analysis Plan: Final Analysis

View Document

Related Links

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Other Identifiers

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2013-002780-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-292-0106

Identifier Type: -

Identifier Source: org_study_id

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