HIV InfectionsPhase 2/3D3 (Penta21)NCT04337450
DTG/3TC Fixed Dose Formulations for the Maintenance of Virological Suppression in Children With HIV Infection Aged 2 to <15 Years Old
A Phase 2/3 study testing Dolutegravir (DTG) and lamivudine (3TC) and SOC in people with HIV Infections, run by PENTA Foundation at 14 sites in 5 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 2 to 15 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Dolutegravir (DTG) and lamivudine (3TC) and SOC
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 386 participants
- Where
- 14 sitesin 5 countries
- Study dates
- 22 Apr 2022to 30 Sep 2026
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 15 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- HIV-1 infected children who are virologically suppressed for at least the last 6 months prior to enrolment
- Aged 2 to <15 years old
- Weight 6 kg or higher
- Children on the same triple-drug PI/r, NNRTI or INSTI containing ART regimen for at least 3 months
- Girls who have reached menarche must have a negative pregnancy test at screening and randomisation
- Girls who are sexually active must be willing to adhere to highly effective methods of contraception
Show all 10Show fewer
- 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
- 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
- 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
- Participants have no access to weight-appropriate DTG/3TC formulation via their national programme
Who cannot join
- Any previous switch in ART regimen for virological, immunological or clinical treatment failure
- 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
- Evidence of previous resistance to 3TC or INSTI
- Any prior use of regimens consisting of single or dual NRTIs with the exception of a course of zidovudine for PMTCT
- Known allergy or contraindications to dolutegravir or lamivudine
- Diagnosis of tuberculosis and on anti-tuberculosis treatment; children can be enrolled after successful tuberculosis treatment
Show all 17Show fewer
- 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)
- Randomisation visit more than 12 weeks after the most recent screening visit
- Evidence of hepatitis B infection with no protective immunity against hepatitis B: participants positive for HBsAg or HBcAb and negative for HBsAb
- Anticipated need for hepatitis C virus therapy with interferon-based regimen prior to the primary endpoint.
- 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)
- Screening ALT equal to 5 or more times the upper limit of normal ALT (≥5xULN)
- 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)
- Screening creatinine clearance <50 mL/min/1.73m2
- Patients aged ≥6 years at moderate or high risk of suicide as determined by Columbia-Suicide Severity Rating Scale (C-SSRS)
- Girls who are pregnant or breastfeeding
- 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.
Trial locations and contacts
14 sites in 5 countries.
14 sites in 5 countries
Thailand4 sites
Prapokklao Hospital
Chanthaburi
Nakornping Hospital
Chiang Mai
Chiangrai Prachanukroh Hospital
Chiang Rai
Khon Kaen Hospital
Khon Kaen
South Africa3 sites
King Edward VIII Hospital
Durban
PHRU Klerksdorp
Klerksdorp
PHRU
Soweto
Uganda3 sites
Baylor
Kampala
Joint Clinical Research Centre
Kampala
MUJHU
Kampala
United Kingdom3 sites
Birmingham Heartlands Hospital
Birmingham
Great Ormand Street Hospital
London
St. Mary's Hospital
London
About this study
Official title: A Randomised Non-inferiority Trial With Nested PK to Assess DTG/3TC Fixed Dose Formulations for the Maintenance of Virological Suppression in Children With HIV Infection Aged 2 to <15 Years Old
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.
Read the detailed description
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
- HIV Infections
- Being tested
- Dolutegravir (DTG) and lamivudine (3TC), SOC
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dolutegravir (DTG) and lamivudine (3TC)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
SOCDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| SOC | Active comparator | Standard-of-care (SOC) Receives: Drug: SOC |
| DTG/3TC | Experimental | Dolutegravir (DTG) and lamivudine (3TC) (known as DTG/3TC) Receives: Drug: Dolutegravir (DTG) and lamivudine (3TC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 96
Measured: by Week 96
Secondary outcomes (11)
Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 48
Measured: by Week 48
Proportion of children with confirmed HIV-1 RNA ≥50c/mL at weeks 48 and 96 (modified FDA snapshot)
Measured: at Week 48 and 96
Proportion of children with HIV-1 RNA ≥50c/mL at weeks 24, 48 and 96 (including blips and confirmed measures ≥50c/mL)
Measured: at Week 24, 48 and 96
New resistance-associated mutations in those with confirmed HIV-1 RNA ≥50c/mL
Measured: by Week 96
Time to any new or recurrent WHO 3 or WHO 4 event or death
Measured: through study completion, up to 5 years
Change in CD4 (absolute and percentage) from baseline to weeks 24, 48 and 96
Measured: Week 24, 48 and 96
Incidence of serious adverse events, grade 3 and 4 clinical and laboratory adverse events
Measured: through study completion, up to 5 years
Incidence of adverse events leading to discontinuation or modification of the treatment regimen
Measured: through study completion, up to 5 years
Proportion of children with a change in ART for toxicity or switch to second-line
Measured: through study completion, up to 5 years
Change in blood lipids from baseline to weeks 48 and 96
Measured: Week 48 and 96
Change in creatinine clearance estimated using bedside-Schwartz to weeks 48 and 96
Measured: Week 48 and 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2020
- Study start22 Apr 2022
- Primary completion30 Sep 2025
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 386 participants (actual)
Sponsor and investigators
- Lead sponsor
- PENTA Foundation
- Sponsor type
- Research network
- Collaborators
- University College, London, AMS-CMU/IRD (PHPT), Chris Hani Baragwanath Academic Hospital, Durban International Clinical Research Site, Hospital Universitario 12 de Octubre, Prapokklao Hospital, Chantaburi, Chiangrai Prachanukroh Hospital, Nakornping Hospital, Khon Kaen Hospital, Kalasin Hospital, Joint Clinical Research Center, MU-JHU CARE, Baylor College of Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, University Hospital Birmingham NHS Foundation Trust, Department of Clinical Pharmacy, University Medical Centre St Radboud, The Netherlands., Advanced Pathogens Diagnostics Unit, University College London Hospitals, Centre for Health Economics, University of York, Department of Molecular and Clinical Pharmacology, University of Liverpool, St Mary's NHS Trust, Chang Mai Univerity
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04337450
- Sponsor's protocol ID
- D3 (Penta21)
- Acronym
- D3 (Penta21)
- Status last verified
- Mar 2026
- First submitted
- 27 Mar 2020
- Last updated
- 4 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 38636725Botha 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.
PubMed 37766218
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Non-inferiority Trial With Nested PK to Assess DTG/3TC Fixed Dose Formulations for the Maintenance of Virological Suppression in Children With HIV Infection Aged 2 to <15 Years Old
- ClinicalTrials.gov ID
- NCT04337450
- Acronym / sponsor ID
- D3 (Penta21) / D3 (Penta21)
- Conditions
- HIV Infections
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 386 participants (actual)
- Lead sponsor
- PENTA FoundationResearch network
- Collaborators
- University College, London, AMS-CMU/IRD (PHPT), Chris Hani Baragwanath Academic Hospital, Durban International Clinical Research Site, Hospital Universitario 12 de Octubre, Prapokklao Hospital, Chantaburi, Chiangrai Prachanukroh Hospital, Nakornping Hospital, Khon Kaen Hospital, Kalasin Hospital, Joint Clinical Research Center, MU-JHU CARE, Baylor College of Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, University Hospital Birmingham NHS Foundation Trust, Department of Clinical Pharmacy, University Medical Centre St Radboud, The Netherlands., Advanced Pathogens Diagnostics Unit, University College London Hospitals, Centre for Health Economics, University of York, Department of Molecular and Clinical Pharmacology, University of Liverpool, St Mary's NHS Trust, Chang Mai Univerity
- Study start
- 22 Apr 2022 (actual)
- Primary completion
- 30 Sep 2025 (actual)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 7 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SOC | Active comparator | Drug: SOCStandard-of-care (SOC) |
| DTG/3TC | Experimental | Drug: Dolutegravir (DTG) and lamivudine (3TC)Dolutegravir (DTG) and lamivudine (3TC) (known as DTG/3TC) |
Who may qualify
- Ages
- 2 to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- HIV-1 infected children who are virologically suppressed for at least the last 6 months prior to enrolment
- Aged 2 to <15 years old
- Weight 6 kg or higher
- Children on the same triple-drug PI/r, NNRTI or INSTI containing ART regimen for at least 3 months
- Girls who have reached menarche must have a negative pregnancy test at screening and randomisation
Key exclusion criteria (17 listed)
- Any previous switch in ART regimen for virological, immunological or clinical treatment failure
- 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
- Evidence of previous resistance to 3TC or INSTI
- Any prior use of regimens consisting of single or dual NRTIs with the exception of a course of zidovudine for PMTCT
- Known allergy or contraindications to dolutegravir or lamivudine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Drug | DTG/3TC |
| SOC2 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) | Drug | SOC |
Primary outcome
Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 96
Time frame: by Week 96
11 secondary outcomes
Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 48
Time frame: by Week 48
Proportion of children with confirmed HIV-1 RNA ≥50c/mL at weeks 48 and 96 (modified FDA snapshot)
Time frame: at Week 48 and 96
Proportion of children with HIV-1 RNA ≥50c/mL at weeks 24, 48 and 96 (including blips and confirmed measures ≥50c/mL)
Time frame: at Week 24, 48 and 96
New resistance-associated mutations in those with confirmed HIV-1 RNA ≥50c/mL
Time frame: by Week 96
Time to any new or recurrent WHO 3 or WHO 4 event or death
Time frame: through study completion, up to 5 years
Change in CD4 (absolute and percentage) from baseline to weeks 24, 48 and 96
Time frame: Week 24, 48 and 96
Incidence of serious adverse events, grade 3 and 4 clinical and laboratory adverse events
Time frame: through study completion, up to 5 years
Incidence of adverse events leading to discontinuation or modification of the treatment regimen
Time frame: through study completion, up to 5 years
Proportion of children with a change in ART for toxicity or switch to second-line
Time frame: through study completion, up to 5 years
Change in blood lipids from baseline to weeks 48 and 96
Time frame: Week 48 and 96
Change in creatinine clearance estimated using bedside-Schwartz to weeks 48 and 96
Time frame: Week 48 and 96
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2026.
- Derived from this study: PubMed 38636725Turkova 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.
- Derived from this study: PubMed 37766218Botha 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.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
14 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Dolutegravir (DTG) and lamivudine (3TC) and SOC in people with HIV Infections, run by PENTA Foundation at 14 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Thailand, South Africa, Uganda, United Kingdom, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 96 (time frame: by Week 96). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04337450, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2026.