HIV InfectionPhase 2/3NCT02259127
ODYSSEY (PENTA 20)
A Phase 2/3 study testing Dolutegravir in people with HIV Infection, run by PENTA Foundation at 28 sites in 8 countries.
Trial summary
A new anti-HIV medicine (Dolutegravir) combined with 2 currently used anti-HIV medicines is non-inferior to the standard combination of medicines used in terms of efficacy and better in terms of toxicity. Read more about this study
- Who is it for?
- Ages 28 days to 18 years
- Conditions the study is for
- HIV Infection
- What is being tested?
- Dolutegravir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 792 participants
- Where
- 28 sitesin 8 countries
- Study dates
- 20 Sep 2016to 7 Dec 2023
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 28 days to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- ALL PATIENTS:
- Children ≥28 days and <18 years weighing ≥3kg with confirmed HIV-1 infection
- Parents/carers and children, where applicable, give informed written consent
- Girls aged 12 years or older who have reached menses must have a negative pregnancy test at screening and be willing to adhere to effective methods of contraception if sexually active
- Children with co-infections who need to start ART can be enrolled into ODYSSEY according to local/national guidelines
- Parents/carers and children, where applicable, willing to adhere to a minimum of 96 weeks' follow-up
Show all 16Show fewer
- Children weighing 3 to <14kg must be eligible and willing to participate in the Weight band (WB)-Pharmacokinetics (PK)1 substudy unless direct enrolment for the child's weight band has opened following the WB-PK1 substudy and/or dosing information has become available from the IMPAACT P1093 DTG dose-finding study.
- ADDITIONAL CRITERIA FOR ODYSSEY A:
- Planning to start first-line ART
- ADDITIONAL CRITERIA FOR ODYSSEY B:
- Planning to start second-line ART defined as either: (i) switch of at least 2 ART drugs due to treatment failure; or (ii) switch of only the third agent due to treatment failure where drug sensitivity tests show no mutations conferring Nucleoside Reverse Transcriptase Inhibitor (NRTI) resistance
- Treated with only one previous ART regimen. Single drug substitutions for toxicity, simplification, changes in national guidelines or drug availability are allowed
- At least one NRTI with predicted preserved activity available for a background regimen
- In settings where resistance tests are routinely available, at least one new active NRTI from tenofovir disoproxil fumarate, abacavir or zidovudine should have preserved activity based on cumulative results of resistance tests
- In settings where resistance tests are not routinely available, children who are due to switch according to national guidelines should have at least one new NRTI predicted to be available from tenofovir disoproxil fumarate, abacavir or zidovudine
- Viral load ≥ 500 c/ml at screening visit
Who cannot join
- History or presence of known allergy or contraindications to dolutegravir
- History or presence of known allergy or contraindications to proposed available NRTI backbone or proposed available SOC third agent.
- Alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal, OR ALT ≥3x upper limit of normal and bilirubin ≥2x upper limit of normal
- 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), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- Anticipated need for Hepatitis C virus (HCV) therapy during the study
- Pregnancy or breastfeeding
- Evidence of lack of susceptibility to integrase inhibitors or more than a 2-week exposure to antiretrovirals of this class
Trial locations and contacts
28 sites in 8 countries.
28 sites in 8 countries
Thailand6 sites
Prapokklao Hospital
Chanthaburi
Nakornping Hospital
Chiang Mai
Chiangrai Prachanukroh Hospital
Chiang Rai
Khon Kaen Hospital
Khon Kaen
Mahasarakam Hospital
Maha Sarakham
Phayao Hospital
Phayao
United Kingdom6 sites
Birmingham Heartlands Hospital
Birmingham
Leeds General Infirmary
Leeds
Leicester Royal Infirmary
Leicester
Great Ormand Street Hospital
London
Kings College Hospital
London
St Mary's Hospital
London
South Africa5 sites
King Edward VIII Hospital
Durban
Africa Health Research Institute (AHRI)
Hlabisa
PHRU Klerksdorp
Klerksdorp
Kid-Cru
Parow
PHRU
Soweto
Spain3 sites
Hospital San Joan de Defu
Barcelona
Hospital 12 de Octubre
Madrid
Hospital La Paz
Madrid
About this study
Official title: A Randomised Trial of Dolutegravir (DTG)-Based Antiretroviral Therapy vs. Standard of Care (SOC) in Children With HIV Infection Starting First-line or Switching to Second-line ART
A new anti-HIV medicine (Dolutegravir) combined with 2 currently used anti-HIV medicines is non-inferior to the standard combination of medicines used in terms of efficacy and better in terms of toxicity.
Read the detailed description
The ODYSSEY study was an international randomised trial evaluating dolutegravir based antiretroviral therapy (ART) versus standard of care in HIV-infected children aged less than 18 years who were starting first line treatment (ODYSSEY A) or switching to second line treatment (ODYSSEY B). Participants had visits 4 weeks and 12 weeks after randomisation and every 12 weeks subsequent of that. They were followed up for a minimum of 96 weeks. The primary objective of the study was to assess the difference in virological or clinical failure by 96 weeks between children receiving a DTG-based regimen and those on standard of care.
At the end of study visit for the randomised phase, children and carers were invited to consent to extended follow-up. Children's visit schedules and care were as per local clinic guidelines. Participants were followed up until July 2023 in this phase of the trial. The objectives of the extended follow-up were two-fold: 1. to provide safety data for ViiV Healthcare for participants who, in the opinion of the treating physician, continue to derive benefit from dolutegravir and receive dolutegravir from ViiV Healthcare where it was not available through their country's national HIV treatment programme; 2. to monitor long-term safety and effectiveness of dolutegravir versus standard of care.
- Conditions
- HIV Infection
- Being tested
- Dolutegravir, Standard of Care
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DolutegravirDrug
Also called DTG
Standard of CareDrug
Also called SOC
PI or non nucleoside transcriptase inhibitors
| Study group | Role | What they receive |
|---|---|---|
| SOC arm | Active comparator | Standard of Care (SOC) for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors Receives: Drug: Standard of Care |
| DTG arm | Experimental | DTG + 2 nucleoside transcriptase inhibitors Receives: Drug: Dolutegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Proportion With Failure (Clinical or Virological)
Treatment failure by 96 weeks.
Estimated using time to the first occurrence of any of the following components:
- Insufficient virological response defined as < 1 log10 drop at week 24 and switch to second/third line ART for treatment failure
- Viral Load (VL)>400 c/ml at or after 36 weeks confirmed by next visit
- Death due to any cause
- Any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events, adjudicated by the Endpoint Review Committee
Measured: 96 weeks post randomisation
Secondary outcomes (25)
HIV-1 RNA <50c/ml at 96 Weeks
Proportion of children with viral load suppression <50 c/ml at 96 weeks.
Measured: 96 weeks post randomisation
HIV-1 RNA <400c/mL at 96 Weeks
Proportion of children with viral load suppression <400 c/ml at 96 weeks
Measured: 96 weeks post randomisation
Mean Change in CD4 Count From Baseline to Week 96
Reporting mean change from the global baseline value across both arms.
Measured: 96 weeks post randomisation
Mean Change in Total Cholesterol From Baseline to Week 96
Reporting mean change from global baseline value across both arms.
Measured: 96 weeks post randomisation
Serious Adverse Events
Incidence of serious adverse events
Measured: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).
Grade 3 or Above Clinical and Laboratory Adverse Events
Incidence of new clinical and laboratory grade 3 and 4 adverse events
Measured: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).
Adverse Events Leading to ART Modification Any Grade
Incidence of adverse events (of any grade) leading to treatment modification
Measured: Randomised Phase
Treatment Failure by 48 Weeks
Treatment failure by 48 weeks. Difference in proportion with clinical or virological failure (as defined above)
Measured: 48 weeks post randomisation
Treatment Failure by 144 Weeks
Treatment failure by 144 weeks. Difference in proportion with clinical or virological failure (as defined above)
Measured: 144 weeks post randomisation
WHO 4, Severe WHO 3 Events and Death
Rate of clinical events : WHO 4, severe WHO 3 events and death
Measured: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).
Per Protocol: Treatment Failure by 96 Weeks
Per protocol: treatment failure by 96 weeks post randomisation
Measured: 96 weeks post randomisation
Any Drug Class Resistance After Virologic Failure
Any drug class resistance after virologic failure 96 weeks post randomisation
Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.
Measured: 96 weeks post randomisation
NRTI Resistance After Virologic Failure
NRTI resistance after virologic failure 96 weeks post randomisation.
Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.
Measured: 96 weeks post randomisation
NNRTI Resistance After Virologic Failure
NNRTI resistance after virologic failure 96 weeks post randomisation.
Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.
Measured: 96 weeks post randomisation
PI Resistance After Virologic Failure
PI resistance after virologic failure 96 weeks post randomisation.
Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.
Measured: 96 weeks post randomisation
INSTI Resistance After Virologic Failure
INSTI resistance after virologic failure 96 weeks post randomisation
Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.
Measured: 96 weeks post randomisation
Emerging Resistance to Any Drug Class After Virologic Failure
Emerging resistance to any drug class after virologic failure 96 weeks post randomisation
Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.
>=14kg cohort: among participants with virologic failure and exposure to the drug class, percentage of participants with emerging resistance was estimated under an assumption of the same proportion of new resistance in participants with an available baseline resistance test and those without.
<14kg cohort: percentage reported for participants with whom resistance test was available post-failure and at baseline, and exposed to drug-class during trial.
Measured: 96 weeks post randomisation
NRTI Emerging Resistance After Virologic Failure
NRTI emerging resistance after virologic failure 96 weeks post randomisation
Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.
>=14kg cohort: among participants with virologic failure and exposure to the drug class, percentage of participants with emerging resistance was estimated under an assumption of the same proportion of new resistance in participants with an available baseline resistance test and those without.
<14kg cohort: percentage reported for participants with whom a resistance test was available post-failure and at baseline, and exposed to drug-class during trial.
Measured: 96 weeks post randomisation
NNRTI Emerging Resistance After Virologic Failure
NNRTI emerging resistance after virologic failure 96 weeks post randomisation
Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.
>=14kg cohort: among participants with virologic failure and exposure to the drug class, percentage of participants with emerging resistance was estimated under an assumption of the same proportion of new resistance in participants with an available baseline resistance test and those without.
<14kg cohort: percentage reported for participants with whom a resistance test was available post-failure and at baseline, and exposed to drug-class during trial.
Measured: 96 weeks post randomisation
PI Emerging Resistance After Virologic Failure
PI emerging resistance after virologic failure 96 weeks post randomisation
Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.
>=14kg cohort: among participants with virologic failure and exposure to the drug class, percentage of participants with emerging resistance was estimated under an assumption of the same proportion of new resistance in participants with an available baseline resistance test and those without.
<14kg cohort: percentage reported for participants with whom a resistance test was available post-failure and at baseline, and exposed to drug-class during trial.
Measured: 96 weeks post randomisation
INSTI Emerging Resistance After Virologic Failure
INSTI emerging resistance after virologic failure 96 weeks post randomisation
Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.
>=14kg cohort: among participants with virologic failure and exposure to the drug class, percentage of participants with emerging resistance was estimated under an assumption of the same proportion of new resistance in participants with an available baseline resistance test and those without.
<14kg cohort: percentage reported for participants with whom a resistance test was available post-failure and at baseline, and exposed to drug-class during trial.
The integrase gene was not sequenced for the standard of care arm.
Measured: 96 weeks post randomisation
Time to Any New or Recurrent AIDS Defining Event (WHO 4) or Severe WHO 3 Events
Time to any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events adjudicated by the Endpoint Review Committee.
Reported in >=14kg and <14kg papers. >=14kg cohort paper (https://www.nejm.org/doi/full/10.1056/NEJMoa2108793) <14kg cohort paper (https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00163-1/fulltext)
Measured: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).
Adherence Questionnaire
The proportion of adherence questionnaires where the participant/carer reports missing a dose within the last week will be compared between randomised groups.
Reported in >=14kg and <14kg papers. >=14kg cohort paper (https://www.nejm.org/doi/full/10.1056/NEJMoa2108793) <14kg cohort paper (https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00163-1/fulltext)
Measured: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).
Health-related Quality of Life Questionnaire
Adapted from the Euro Quality of Life Questionnaire (Qol)-5D questionnaire The EQ5D-3L (3-level version of EQ-5D) questionnaire contains five questions about the participants' quality of life: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Each question has three dimensions: no problems, some problems, and extreme problems.
This analysis reports whether the participant reports any problems (some or extreme). Percentages are of participants completing at least one EQ5D-3L questionnaire during follow-up.
Reported in >=14kg cohort paper (https://www.nejm.org/doi/full/10.1056/NEJMoa2108793)
Measured: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).
Acceptability Questionnaire
Number of participants reported to have problems with size, taste or swallowing of the medicines as assessed by Acceptability questionnaire
Reported in >=14kg and <14kg papers. >=14kg cohort paper (https://www.nejm.org/doi/full/10.1056/NEJMoa2108793) <14kg cohort paper (https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00163-1/fulltext)
Measured: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2014 (estimated)
- Study start20 Sep 2016
- Primary completion2 Mar 2021
- Study completion7 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies 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
- 792 participants (actual)
Sponsor and investigators
- Lead sponsor
- PENTA Foundation
- Sponsor type
- Research network
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Program for HIV Prevention and Treatment (PHPT), ViiV Healthcare, University College, London
- Responsible party
- Sponsor
- Investigators
- Diana Gibb, Principal investigator, Medical Research Council Clinical Trials Unit at UCL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02259127
- Sponsor's protocol ID
- ODYSSEY (PENTA 20)
- Other IDs
- 2014-002632-14, 2014
- Status last verified
- Jul 2025
- First submitted
- 30 Sep 2014
- Last updated
- 29 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Turkova A, White E, Mujuru HA, Kekitiinwa AR, Kityo CM, Violari A, Lugemwa A, Cressey TR, Musoke P, Variava E, Cotton MF, Archary M, Puthanakit T, Behuhuma O, Kobbe R, Welch SB, Bwakura-Dangarembizi M, Amuge P, Kaudha E, Barlow-Mosha L, Makumbi S, Ramsagar N, Ngampiyaskul C, Musoro G, Atwine L, Liberty A, Musiime V, Bbuye D, Ahimbisibwe GM, Chalermpantmetagul S, Ali S, Sarfati T, Wynne B, Shakeshaft C, Colbers A, Klein N, Bernays S, Saidi Y, Coelho A, Grossele T, Compagnucci A, Giaquinto C, Rojo P, Ford D, Gibb DM; ODYSSEY Trial Team. Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children. N Engl J Med. 2021 Dec 30;385(27):2531-2543. doi: 10.1056/NEJMoa2108793.
PubMed 34965338Amuge P, Lugemwa A, Wynne B, Mujuru HA, Violari A, Kityo CM, Archary M, Variava E, White E, Turner RM, Shakeshaft C, Ali S, Nathoo KJ, Atwine L, Liberty A, Bbuye D, Kaudha E, Mngqibisa R, Mosala M, Mumbiro V, Nanduudu A, Ankunda R, Maseko L, Kekitiinwa AR, Giaquinto C, Rojo P, Gibb DM, Turkova A, Ford D; ODYSSEY Trial Team. Once-daily dolutegravir-based antiretroviral therapy in infants and children living with HIV from age 4 weeks: results from the below 14 kg cohort in the randomised ODYSSEY trial. Lancet HIV. 2022 Sep;9(9):e638-e648. doi: 10.1016/S2352-3018(22)00163-1.
PubMed 36055295Turkova A, White E, Violari A, Mujuru HA, Kekitiinwa AR, Lugemwa A, Kaudha E, Na-Rajsima S, Ahimbisibwe GM, Variavae E, Archary M, Akhalwaya Y, Puthanakit T, Bwakura-Dangarembizi M, Bbuye D, Kasozi M, Liberty A, Konigs C, Welch SB, Riault Y, Bamford A, Cressey TR, Musoke P, Kityo C, Ferrand R, Giaquinto C, Rojo P, Gibb DM, Ford D; ODYSSEY trial team. Weight gain, body composition, and metabolic parameters of dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: an ancillary analysis of the ODYSSEY trial. Lancet Child Adolesc Health. 2026 Mar;10(3):189-202. doi: 10.1016/S2352-4642(25)00339-6. Epub 2026 Jan 21.
PubMed 41579881White E, Kityo C, Spyer MJ, Mujuru HA, Nankya I, Kekitiinwa AR, Lugemwa A, Kaudha E, Liberty A, Cassim H, Archary M, Cotton MF, Ahimbisibwe GM, Cressey TR, Ngampiyaskul C, Srirompotong U, Behuhuma O, Saidi Y, Bamford A, Kobbe R, Nastouli E, Rojo P, Giaquinto C, Gibb DM, Ford D, Turkova A; ODYSSEY trial team. Virological outcomes and genotypic resistance on dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial. Lancet HIV. 2025 Mar;12(3):e201-e213. doi: 10.1016/S2352-3018(24)00155-3. Epub 2025 Feb 17.
PubMed 39978387Barlow-Mosha LN, Ahimbisibwe GM, Chappell E, Amuge PM, Nanduudu A, Kaudha E, Amukele T, Balamusani D, Kafufu B, Nimwesiga A, Kataike H, Namwanje R, Kasangaki G, Mulindwa A, Muzorah GA, Bbuye D, Musiime V, Mujyambere E, Ssenyonga M, Mulima D, Kyambadde RC, Namusanje J, Isabirye R, Nabalamba M, Nakirya BM, Kityo C, Kekitiinwa AR, Giaquinto C, Copp A, Gibb DM, Ford D, Musoke P, Turkova A; ODYSSEY trial team. Effect of dolutegravir on folate, vitamin B12 and mean corpuscular volume levels among children and adolescents with HIV: a sub-study of the ODYSSEY randomized controlled trial. J Int AIDS Soc. 2023 Sep;26(9):e26174. doi: 10.1002/jia2.26174.
PubMed 37766505Turkova A, Waalewijn H, Chan MK, Bollen PDJ, Bwakura-Dangarembizi MF, Kekitiinwa AR, Cotton MF, Lugemwa A, Variava E, Ahimbisibwe GM, Srirompotong U, Mumbiro V, Amuge P, Zuidewind P, Ali S, Kityo CM, Archary M, Ferrand RA, Violari A, Gibb DM, Burger DM, Ford D, Colbers A; ODYSSEY Trial Team. Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial. Lancet HIV. 2022 Sep;9(9):e627-e637. doi: 10.1016/S2352-3018(22)00160-6. Epub 2022 Jul 19.
PubMed 35868341Singh RP, Adkison KK, Baker M, Parasrampuria R, Wolstenholme A, Davies M, Sewell N, Brothers C, Buchanan AM. Development of Dolutegravir Single-entity and Fixed-dose Combination Formulations for Children. Pediatr Infect Dis J. 2022 Mar 1;41(3):230-237. doi: 10.1097/INF.0000000000003366.
PubMed 34817414Moore CL, Turkova A, Mujuru H, Kekitiinwa A, Lugemwa A, Kityo CM, Barlow-Mosha LN, Cressey TR, Violari A, Variava E, Cotton MF, Archary M, Compagnucci A, Puthanakit T, Behuhuma O, Saiotadi Y, Hakim J, Amuge P, Atwine L, Musiime V, Burger DM, Shakeshaft C, Giaquinto C, Rojo P, Gibb DM, Ford D; ODYSSEY Trial Team. ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing. BMC Infect Dis. 2021 Jan 4;21(1):5. doi: 10.1186/s12879-020-05672-6.
PubMed 33446115Bollen PDJ, Moore CL, Mujuru HA, Makumbi S, Kekitiinwa AR, Kaudha E, Parker A, Musoro G, Nanduudu A, Lugemwa A, Amuge P, Hakim JG, Rojo P, Giaquinto C, Colbers A, Gibb DM, Ford D, Turkova A, Burger DM; ODYSSEY trial team. Simplified dolutegravir dosing for children with HIV weighing 20 kg or more: pharmacokinetic and safety substudies of the multicentre, randomised ODYSSEY trial. Lancet HIV. 2020 Aug;7(8):e533-e544. doi: 10.1016/S2352-3018(20)30189-2.
PubMed 32763217
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Trial of Dolutegravir (DTG)-Based Antiretroviral Therapy vs. Standard of Care (SOC) in Children With HIV Infection Starting First-line or Switching to Second-line ART
- ClinicalTrials.gov ID
- NCT02259127
- Acronym / sponsor ID
- ODYSSEY (PENTA 20)
- Conditions
- HIV Infection
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 792 participants (actual)
- Lead sponsor
- PENTA FoundationResearch network
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Program for HIV Prevention and Treatment (PHPT), ViiV Healthcare, University College, London
- Study start
- 20 Sep 2016 (actual)
- Primary completion
- 2 Mar 2021 (actual)
- Study completion
- 7 Dec 2023 (actual)
- First posted
- 8 Oct 2014 (estimated)
- Results
- Posted 29 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A new anti-HIV medicine (Dolutegravir) combined with 2 currently used anti-HIV medicines is non-inferior to the standard combination of medicines used in terms of efficacy and better in terms of toxicity.
Detailed description
The ODYSSEY study was an international randomised trial evaluating dolutegravir based antiretroviral therapy (ART) versus standard of care in HIV-infected children aged less than 18 years who were starting first line treatment (ODYSSEY A) or switching to second line treatment (ODYSSEY B). Participants had visits 4 weeks and 12 weeks after randomisation and every 12 weeks subsequent of that. They were followed up for a minimum of 96 weeks. The primary objective of the study was to assess the difference in virological or clinical failure by 96 weeks between children receiving a DTG-based regimen and those on standard of care.
At the end of study visit for the randomised phase, children and carers were invited to consent to extended follow-up. Children's visit schedules and care were as per local clinic guidelines. Participants were followed up until July 2023 in this phase of the trial. The objectives of the extended follow-up were two-fold: 1. to provide safety data for ViiV Healthcare for participants who, in the opinion of the treating physician, continue to derive benefit from dolutegravir and receive dolutegravir from ViiV Healthcare where it was not available through their country's national HIV treatment programme; 2. to monitor long-term safety and effectiveness of dolutegravir versus standard of care.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SOC arm | Active comparator | Drug: Standard of CareStandard of Care (SOC) for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors |
| DTG arm | Experimental | Drug: DolutegravirDTG + 2 nucleoside transcriptase inhibitors |
Who may qualify
- Ages
- 28 days to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (16 listed)
- Children ≥28 days and <18 years weighing ≥3kg with confirmed HIV-1 infection
- Parents/carers and children, where applicable, give informed written consent
- Girls aged 12 years or older who have reached menses must have a negative pregnancy test at screening and be willing to adhere to effective methods of contraception if sexually active
- Children with co-infections who need to start ART can be enrolled into ODYSSEY according to local/national guidelines
- Parents/carers and children, where applicable, willing to adhere to a minimum of 96 weeks' follow-up
Key exclusion criteria (7 listed)
- History or presence of known allergy or contraindications to dolutegravir
- History or presence of known allergy or contraindications to proposed available NRTI backbone or proposed available SOC third agent.
- Alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal, OR ALT ≥3x upper limit of normal and bilirubin ≥2x upper limit of normal
- 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), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- Anticipated need for Hepatitis C virus (HCV) therapy during the study
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 |
|---|---|---|
| DolutegravirAlso: DTG | Drug | DTG arm |
| Standard of CareAlso: SOCPI or non nucleoside transcriptase inhibitors | Drug | SOC arm |
Primary outcome
Difference in Proportion With Failure (Clinical or Virological)
Time frame: 96 weeks post randomisation
Treatment failure by 96 weeks. Estimated using time to the first occurrence of any of the following components: * Insufficient virological response defined as < 1 log10 drop at week 24 and switch to second/third line ART for treatment failure * Viral Load (VL)>400 c/ml at or after 36 weeks confirmed by next visit * Death due to any cause * Any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events, adjudicated by the Endpoint Review Committee
25 secondary outcomes
HIV-1 RNA <50c/ml at 96 Weeks
Time frame: 96 weeks post randomisation
HIV-1 RNA <400c/mL at 96 Weeks
Time frame: 96 weeks post randomisation
Mean Change in CD4 Count From Baseline to Week 96
Time frame: 96 weeks post randomisation
Mean Change in Total Cholesterol From Baseline to Week 96
Time frame: 96 weeks post randomisation
Serious Adverse Events
Time frame: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).
Grade 3 or Above Clinical and Laboratory Adverse Events
Time frame: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).
Adverse Events Leading to ART Modification Any Grade
Time frame: Randomised Phase
Treatment Failure by 48 Weeks
Time frame: 48 weeks post randomisation
Treatment Failure by 144 Weeks
Time frame: 144 weeks post randomisation
WHO 4, Severe WHO 3 Events and Death
Time frame: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).
Per Protocol: Treatment Failure by 96 Weeks
Time frame: 96 weeks post randomisation
Any Drug Class Resistance After Virologic Failure
Time frame: 96 weeks post randomisation
NRTI Resistance After Virologic Failure
Time frame: 96 weeks post randomisation
NNRTI Resistance After Virologic Failure
Time frame: 96 weeks post randomisation
PI Resistance After Virologic Failure
Time frame: 96 weeks post randomisation
INSTI Resistance After Virologic Failure
Time frame: 96 weeks post randomisation
Emerging Resistance to Any Drug Class After Virologic Failure
Time frame: 96 weeks post randomisation
NRTI Emerging Resistance After Virologic Failure
Time frame: 96 weeks post randomisation
NNRTI Emerging Resistance After Virologic Failure
Time frame: 96 weeks post randomisation
PI Emerging Resistance After Virologic Failure
Time frame: 96 weeks post randomisation
INSTI Emerging Resistance After Virologic Failure
Time frame: 96 weeks post randomisation
Time to Any New or Recurrent AIDS Defining Event (WHO 4) or Severe WHO 3 Events
Time frame: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).
Adherence Questionnaire
Time frame: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).
Health-related Quality of Life Questionnaire
Time frame: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).
Acceptability Questionnaire
Time frame: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 34965338Turkova A, White E, Mujuru HA, Kekitiinwa AR, Kityo CM, Violari A, Lugemwa A, Cressey TR, Musoke P, Variava E, Cotton MF, Archary M, Puthanakit T, Behuhuma O, Kobbe R, Welch SB, Bwakura-Dangarembizi M, Amuge P, Kaudha E, Barlow-Mosha L, Makumbi S, Ramsagar N, Ngampiyaskul C, Musoro G, Atwine L, Liberty A, Musiime V, Bbuye D, Ahimbisibwe GM, Chalermpantmetagul S, Ali S, Sarfati T, Wynne B, Shakeshaft C, Colbers A, Klein N, Bernays S, Saidi Y, Coelho A, Grossele T, Compagnucci A, Giaquinto C, Rojo P, Ford D, Gibb DM; ODYSSEY Trial Team. Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children. N Engl J Med. 2021 Dec 30;385(27):2531-2543. doi: 10.1056/NEJMoa2108793.
- Results publication: PubMed 36055295Amuge P, Lugemwa A, Wynne B, Mujuru HA, Violari A, Kityo CM, Archary M, Variava E, White E, Turner RM, Shakeshaft C, Ali S, Nathoo KJ, Atwine L, Liberty A, Bbuye D, Kaudha E, Mngqibisa R, Mosala M, Mumbiro V, Nanduudu A, Ankunda R, Maseko L, Kekitiinwa AR, Giaquinto C, Rojo P, Gibb DM, Turkova A, Ford D; ODYSSEY Trial Team. Once-daily dolutegravir-based antiretroviral therapy in infants and children living with HIV from age 4 weeks: results from the below 14 kg cohort in the randomised ODYSSEY trial. Lancet HIV. 2022 Sep;9(9):e638-e648. doi: 10.1016/S2352-3018(22)00163-1.
- Derived from this study: PubMed 41579881Turkova A, White E, Violari A, Mujuru HA, Kekitiinwa AR, Lugemwa A, Kaudha E, Na-Rajsima S, Ahimbisibwe GM, Variavae E, Archary M, Akhalwaya Y, Puthanakit T, Bwakura-Dangarembizi M, Bbuye D, Kasozi M, Liberty A, Konigs C, Welch SB, Riault Y, Bamford A, Cressey TR, Musoke P, Kityo C, Ferrand R, Giaquinto C, Rojo P, Gibb DM, Ford D; ODYSSEY trial team. Weight gain, body composition, and metabolic parameters of dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: an ancillary analysis of the ODYSSEY trial. Lancet Child Adolesc Health. 2026 Mar;10(3):189-202. doi: 10.1016/S2352-4642(25)00339-6. Epub 2026 Jan 21.
- Derived from this study: PubMed 39978387White E, Kityo C, Spyer MJ, Mujuru HA, Nankya I, Kekitiinwa AR, Lugemwa A, Kaudha E, Liberty A, Cassim H, Archary M, Cotton MF, Ahimbisibwe GM, Cressey TR, Ngampiyaskul C, Srirompotong U, Behuhuma O, Saidi Y, Bamford A, Kobbe R, Nastouli E, Rojo P, Giaquinto C, Gibb DM, Ford D, Turkova A; ODYSSEY trial team. Virological outcomes and genotypic resistance on dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial. Lancet HIV. 2025 Mar;12(3):e201-e213. doi: 10.1016/S2352-3018(24)00155-3. Epub 2025 Feb 17.
- Derived from this study: PubMed 37766505Barlow-Mosha LN, Ahimbisibwe GM, Chappell E, Amuge PM, Nanduudu A, Kaudha E, Amukele T, Balamusani D, Kafufu B, Nimwesiga A, Kataike H, Namwanje R, Kasangaki G, Mulindwa A, Muzorah GA, Bbuye D, Musiime V, Mujyambere E, Ssenyonga M, Mulima D, Kyambadde RC, Namusanje J, Isabirye R, Nabalamba M, Nakirya BM, Kityo C, Kekitiinwa AR, Giaquinto C, Copp A, Gibb DM, Ford D, Musoke P, Turkova A; ODYSSEY trial team. Effect of dolutegravir on folate, vitamin B12 and mean corpuscular volume levels among children and adolescents with HIV: a sub-study of the ODYSSEY randomized controlled trial. J Int AIDS Soc. 2023 Sep;26(9):e26174. doi: 10.1002/jia2.26174.
- Derived from this study: PubMed 35868341Turkova A, Waalewijn H, Chan MK, Bollen PDJ, Bwakura-Dangarembizi MF, Kekitiinwa AR, Cotton MF, Lugemwa A, Variava E, Ahimbisibwe GM, Srirompotong U, Mumbiro V, Amuge P, Zuidewind P, Ali S, Kityo CM, Archary M, Ferrand RA, Violari A, Gibb DM, Burger DM, Ford D, Colbers A; ODYSSEY Trial Team. Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial. Lancet HIV. 2022 Sep;9(9):e627-e637. doi: 10.1016/S2352-3018(22)00160-6. Epub 2022 Jul 19.
- Derived from this study: PubMed 34817414Singh RP, Adkison KK, Baker M, Parasrampuria R, Wolstenholme A, Davies M, Sewell N, Brothers C, Buchanan AM. Development of Dolutegravir Single-entity and Fixed-dose Combination Formulations for Children. Pediatr Infect Dis J. 2022 Mar 1;41(3):230-237. doi: 10.1097/INF.0000000000003366.
- Derived from this study: PubMed 33446115Moore CL, Turkova A, Mujuru H, Kekitiinwa A, Lugemwa A, Kityo CM, Barlow-Mosha LN, Cressey TR, Violari A, Variava E, Cotton MF, Archary M, Compagnucci A, Puthanakit T, Behuhuma O, Saiotadi Y, Hakim J, Amuge P, Atwine L, Musiime V, Burger DM, Shakeshaft C, Giaquinto C, Rojo P, Gibb DM, Ford D; ODYSSEY Trial Team. ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing. BMC Infect Dis. 2021 Jan 4;21(1):5. doi: 10.1186/s12879-020-05672-6.
- Derived from this study: PubMed 32763217Bollen PDJ, Moore CL, Mujuru HA, Makumbi S, Kekitiinwa AR, Kaudha E, Parker A, Musoro G, Nanduudu A, Lugemwa A, Amuge P, Hakim JG, Rojo P, Giaquinto C, Colbers A, Gibb DM, Ford D, Turkova A, Burger DM; ODYSSEY trial team. Simplified dolutegravir dosing for children with HIV weighing 20 kg or more: pharmacokinetic and safety substudies of the multicentre, randomised ODYSSEY trial. Lancet HIV. 2020 Aug;7(8):e533-e544. doi: 10.1016/S2352-3018(20)30189-2.
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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.
Diana Gibb principal investigator
Medical Research Council Clinical Trials Unit at UCL
28 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Dolutegravir in people with HIV Infection, run by PENTA Foundation at 28 sites in 8 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 16 inclusion and 7 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: finished, as of the sponsor's last update on 29 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in Thailand, United Kingdom, South Africa, Uganda, Spain and 3 more countries. 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?
Yes. Results are posted in the registry (first posted 29 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Difference in Proportion With Failure (Clinical or Virological) (time frame: 96 weeks post randomisation). 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 NCT02259127, which also lists 9 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 29 Jul 2025.