DTG/3TC Fixed Dose Formulations for the Maintenance of Virological Suppression in Children With HIV Infection Aged 2 to <15 Years Old

NCT ID: NCT04337450

Last Updated: 2025-09-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

386 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-22

Study Completion Date

2025-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This study aims to find out whether treating children and young people living with HIV with two anti HIV medicines, dolutegravir and lamivudine, is safe and as effective as the three-medicine anti-HIV treatments currently used in routine practice.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This study will include 370 children and young people aged 2 to less than 15 years old who are living with HIV and are being treated with anti-HIV medicines for the first time. Participants will be split into two groups, by chance, by a process called "randomisation". One group will continue to receive the anti-HIV medicines already taken according to country-specific routine practice. The second group will change to the new combination of medicine, dolutegravir and lamivudine (with the combination written usually as "DTG/3TC"). Depending on the weight, participants in the second group will be able take the new medicine either as one tablet a day or as a small number of dispersible tablets that are also taken once a day. All children and young people in the study will have regular clinic assessments that are at a similar frequency to the clinic visits that participants would have outside of the study. Blood tests will be performed to check that the medicine is safe and, at some visits, participants and their carers will also be asked to answer some questions on how they feel about taking their medicine. All children and young people will be followed until the last participant who joins the study has been in the study for 96 weeks.

After 96 weeks, children who were randomised to the DTG/3TC arm will enter the extended follow-up continuing to receive DTG/3TC.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

HIV Infections

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

SOC

Standard-of-care (SOC)

Group Type ACTIVE_COMPARATOR

SOC

Intervention Type DRUG

2 nucleos(t)ide reverse transcriptase inhibitor (NRTI) and a third (anchor) drug (either an integrase strand transfer inhibitor (INSTI), a protease inhibitor (PI) or a non- nucleoside reverse transcriptase inhibitor (NNRTI)

DTG/3TC

Dolutegravir (DTG) and lamivudine (3TC) (known as DTG/3TC)

Group Type EXPERIMENTAL

Dolutegravir (DTG) and lamivudine (3TC)

Intervention Type DRUG

Children randomised to the DTG/3TC arm will receive once daily DTG/3TC fixed dose combination dispersible or film-coated tablets dosed using WHO weight bands criteria

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Dolutegravir (DTG) and lamivudine (3TC)

Children randomised to the DTG/3TC arm will receive once daily DTG/3TC fixed dose combination dispersible or film-coated tablets dosed using WHO weight bands criteria

Intervention Type DRUG

SOC

2 nucleos(t)ide reverse transcriptase inhibitor (NRTI) and a third (anchor) drug (either an integrase strand transfer inhibitor (INSTI), a protease inhibitor (PI) or a non- nucleoside reverse transcriptase inhibitor (NNRTI)

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. HIV-1 infected children who are virologically suppressed for at least the last 6 months prior to enrolment
2. Aged 2 to \<15 years old
3. Weight 6 kg or higher
4. Children on the same triple-drug PI/r, NNRTI or INSTI containing ART regimen for at least 3 months
5. Girls who have reached menarche must have a negative pregnancy test at screening and randomisation
6. Girls who are sexually active must be willing to adhere to highly effective methods of contraception
7. A parent or legal guardian is willing and able to give informed consent on behalf of the child as per national legislation and willing to adhere to the protocol
8. Participant is willing to give informed assent if the trial site clinician deems them old enough and able to understand the age-appropriate information about participation in the study


1. Participants remain on DTG/3TC at the end of the randomised phase, and in the opinion of the treating physician, derive ongoing benefit from DTG/3TC
2. Participants have no access to weight-appropriate DTG/3TC formulation via their national programme

Exclusion Criteria

1. Any previous switch in ART regimen for virological, immunological or clinical treatment failure
2. Any changes in ART in the last 6 months for reasons other than due to child's growth, drug stock-outs, changes in country guidelines and treatment simplification
3. Evidence of previous resistance to 3TC or INSTI
4. Any prior use of regimens consisting of single or dual NRTIs with the exception of a course of zidovudine for PMTCT
5. Known allergy or contraindications to dolutegravir or lamivudine
6. Diagnosis of tuberculosis and on anti-tuberculosis treatment; children can be enrolled after successful tuberculosis treatment
7. Treatment of co-morbidities with drugs which have significant interactions with antiretroviral treatment, requiring dose adjustment of the study drugs (children can be enrolled after the illness resolves)
8. Randomisation visit more than 12 weeks after the most recent screening visit
9. Evidence of hepatitis B infection with no protective immunity against hepatitis B: participants positive for HBsAg or HBcAb and negative for HBsAb
10. Anticipated need for hepatitis C virus therapy with interferon-based regimen prior to the primary endpoint.
11. Screening ALT equal to 3 or more times the upper limit of normal AND bilirubin equal to 2 or more times the upper limit of normal (ALT ≥3xULN AND bilirubin ≥2xULN)
12. Screening ALT equal to 5 or more times the upper limit of normal ALT (≥5xULN)
13. Patients with severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
14. Screening creatinine clearance \<50 mL/min/1.73m2
15. Patients aged ≥6 years at moderate or high risk of suicide as determined by Columbia-Suicide Severity Rating Scale (C-SSRS)
16. Girls who are pregnant or breastfeeding
17. Children who are in the legal custody of the State and do not have a parent or guardian able to provide informed consent on their behalf.
Minimum Eligible Age

2 Years

Maximum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

MRC CTU at UCL

UNKNOWN

Sponsor Role collaborator

AMS-CMU/IRD (PHPT)

UNKNOWN

Sponsor Role collaborator

Chris Hani Baragwanath Academic Hospital

OTHER

Sponsor Role collaborator

Durban International Clinical Research Site

UNKNOWN

Sponsor Role collaborator

Hospital Universitario 12 de Octubre

OTHER

Sponsor Role collaborator

Prapokklao Hospital, Chantaburi

UNKNOWN

Sponsor Role collaborator

Chiangrai Prachanukroh Hospital

OTHER

Sponsor Role collaborator

Nakornping Hospital

OTHER

Sponsor Role collaborator

Khon Kaen Hospital

OTHER_GOV

Sponsor Role collaborator

Kalasin Hospital

OTHER

Sponsor Role collaborator

Joint Clinical Research Center

OTHER

Sponsor Role collaborator

MU-JHU CARE

OTHER

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role collaborator

Great Ormond Street Hospital for Children NHS Foundation Trust

OTHER

Sponsor Role collaborator

University Hospital Birmingham NHS Foundation Trust

OTHER

Sponsor Role collaborator

Department of Clinical Pharmacy, University Medical Centre St Radboud, The Netherlands.

OTHER

Sponsor Role collaborator

Advanced Pathogens Diagnostics Unit, University College London Hospitals

UNKNOWN

Sponsor Role collaborator

Centre for Health Economics, University of York

UNKNOWN

Sponsor Role collaborator

Department of Molecular and Clinical Pharmacology, University of Liverpool

UNKNOWN

Sponsor Role collaborator

St Mary's NHS Trust

OTHER_GOV

Sponsor Role collaborator

Chang Mai Univerity

UNKNOWN

Sponsor Role collaborator

PENTA Foundation

NETWORK

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

King Edward VIII Hospital

Durban, , South Africa

Site Status

PHRU Klerksdorp

Klerksdorp, , South Africa

Site Status

PHRU

Soweto, , South Africa

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Prapokklao Hospital

Chanthaburi, , Thailand

Site Status

Nakornping Hospital

Chiang Mai, , Thailand

Site Status

Chiangrai Prachanukroh Hospital

Chiang Rai, , Thailand

Site Status

Khon Kaen Hospital

Khon Kaen, , Thailand

Site Status

Baylor

Kampala, , Uganda

Site Status

Joint Clinical Research Centre

Kampala, , Uganda

Site Status

MUJHU

Kampala, , Uganda

Site Status

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Site Status

Great Ormand Street Hospital

London, , United Kingdom

Site Status

St. Mary's Hospital

London, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

South Africa Spain Thailand Uganda United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Turkova A, Chan MK, Kityo C, Kekitiinwa AR, Musoke P, Violari A, Variava E, Archary M, Cressey TR, Chalermpantmetagul S, Sawasdichai K, Ounchanum P, Kanjanavanit S, Srirojana S, Srirompotong U, Welch S, Bamford A, Epalza C, Fortuny C, Colbers A, Nastouli E, Walker S, Carr D, Conway M, Spyer MJ, Parkar N, White I, Nardone A, Thomason MJ, Ferrand RA, Giaquinto C, Ford D; D3 trial team. D3/Penta 21 clinical trial design: A randomised non-inferiority trial with nested drug licensing substudy to assess dolutegravir and lamivudine fixed dose formulations for the maintenance of virological suppression in children with HIV-1 infection, aged 2 to 15 years. Contemp Clin Trials. 2024 Jul;142:107540. doi: 10.1016/j.cct.2024.107540. Epub 2024 Apr 16.

Reference Type DERIVED
PMID: 38636725 (View on PubMed)

Botha JC, Byott M, Spyer MJ, Grant PR, Gartner K, Chen WX, Burton J, Bamford A, Waters LJ, Giaquinto C, Turkova A, Vavro CL, Nastouli E. Sensitive HIV-1 DNA Pol Next-Generation Sequencing for the Characterisation of Archived Antiretroviral Drug Resistance. Viruses. 2023 Aug 25;15(9):1811. doi: 10.3390/v15091811.

Reference Type DERIVED
PMID: 37766218 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

D3 (Penta21)

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.