HIV-1-infectionPhase 3DolPHIN-2NCT03249181
Dolutegravir in Pregnant HIV Mothers and Their Neonates
A Phase 3 study testing Dolutegravir in people with HIV-1-infection and Pregnancy Related, run by University of Liverpool at 2 sites in 2 countries.
Trial summary
To evaluate dolutegravir (DTG) efficacy in women who present with untreated HIV in late pregnancy. An open-label, multi-centre randomised controlled trial of DTG vs efavirenz-based regimens for women commencing cART in late pregnancy. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- HIV-1-infection, Pregnancy Related
- What is being tested?
- Dolutegravir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 268 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 22 Jan 2018to 5 Sep 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Women aged 18 years or older
- Pregnant ( ≥28 weeks gestation by best available gestation estimation)
- Untreated HIV infection in late pregnancy
Who cannot join
- Received any antiretroviral drugs in previous 12 months
- Ever received integrase inhibitors
- Previous documented failure of an NNRTI-containing ART regimen, previous EFV-associated toxicity or other history of ARV use that would preclude randomisation based on investigator judgement
- Serum haemoglobin <8.0 g/dl
- eGFR<50 ml/min*
- Elevations in serum levels of alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN) or ALT >3xULN and bilirubin >2xULN (with >35% direct bilirubin).
Show all 11Show fewer
- History or clinical suspicion of unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hyperbilirubinaemia, oesophageal or gastric varices or persistent jaundice).
- Severe pre-eclampsia (e.g. HELLP), or other pregnancy related events such as renal or liver abnormalities (e.g. grade 2 or above proteinuria,, total bilirubin, ALT or AST)* at the time of enrolment
- Paternal objection for infant participation in DTG arm (where disclosure has taken - applies to Uganda site only
- Medical, psychiatric or obstetric condition that might affect participation in the study based on investigator judgement
- Receiving any of the following medications (current or within past 2 weeks): anti-epileptic drugs, TB therapy, or other drugs known to significantly interact with either DTG or EFV
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
To evaluate dolutegravir (DTG) efficacy in women who present with untreated HIV in late pregnancy.
An open-label, multi-centre randomised controlled trial of DTG vs efavirenz-based regimens for women commencing cART in late pregnancy. HIV positive pregnant women presenting with untreated HIV infection in late (≥28 weeks gestation) pregnancy will be randomised 1:1 to receive DTG (50mg once daily) + 2 nucleoside reverse transcriptase inhibitors (NRTIs) or EFV + 2 NRTIs (SoC)
Read the detailed description
This is an open-label, randomised controlled trial of DTG versus EFV -based regimens for 250 women commencing cART in late pregnancy, randomised 1:1 to DTG vs EFV-based cART. The purpose of this study is to inform treatment guidelines and for the first time specifically address the treatment needs of this group of women- hence the trial is powered for superiority over EFV. The primary endpoints is maternal VL at delivery, with secondary endpoints including safety and tolerability of DTG in both mother and infant, VL decline in breast milk, development of drug resistance, pharmacokinetics of DTG in mother-infant pairs, pharmacogenomics factors relating to efficacy or toxicity of DTG, and MTCT of HIV up to 72 weeks postpartum. Two sites have been selected - Infectious Diseases Institute, Makerere University, Kampala, Uganda and the University of Cape Town, South Africa - both have a strong track record of successfully delivering collaborative multidisciplinary research in PMTCT. Furthermore, health economics analysis to examine costs and cost-effectiveness of DTG in late-presenting pregnant women will be conducted
The desired outcome of this project is to establish high quality evidence and operational guidance for use of DTG in late pregnancy. Late-presenting HIV-infected pregnant women are an important, but neglected group of vulnerable individuals in whom a randomised controlled intervention of HIV treatment has never previously been undertaken. This work will be done in relationship with WHO and the Clinton Health Access Initiative to ensure successful delivery of the project objectives.
- Conditions
- HIV-1-infection, Pregnancy Related
- Being tested
- Dolutegravir, Standard of Care (EFV + 2 NRTI backbone)
- Keywords
- MTCT, Antiretroviral, Pregnancy, Africa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DolutegravirDrug
Patients randomized to the study drug will be commenced on an antiretroviral regimen comprising DTG 50mg once daily in combination with 2 NRTIs
Standard of Care (EFV + 2 NRTI backbone)Drug
Patients randomized to receive standard of care will receive the currently used antiretroviral regimens in keeping with national policy.
| Study group | Role | What they receive |
|---|---|---|
| Dolutegravir | Experimental | Dolutegravir group (DTG+2 NRTIs) - to make best comparison with standard of care, these NRTIs should be those recommended by national policy.
Participants randomized to the study drug will be commenced on an antiretroviral regimen comprising DTG 50mg once daily in combination with 2 NRTIs Receives: Drug: Dolutegravir |
| Standard of Care (EFV + 2 NRTI backbone) | Active comparator | Participants randomized to receive standard of care will receive the currently used antiretroviral regimens in keeping with national policy (EFV + 2NRTIs at both study sites). Receives: Drug: Standard of Care (EFV + 2 NRTI backbone) |
What is being measured
The primary outcome is the main question the study is designed to answer.
HIV Viral Load at Delivery
<50 copies/ mL
Measured: by delivery
Secondary outcomes (5)
Plasma viral load
<1000 copies/ mL
Measured: By delivery
Maternal viral load to 48 weeks
Proportion <50 and <1000 copies/ mL
Measured: 48 weeks postpartum
Maternal viral load to 72 weeks
Proportion <50 and <1000 copies/ mL
Measured: 72 weeks postpartum
Occurrence of MTCT
Proportion of infants with HIV infection
Measured: 48 weeks postpartum
Occurrence of MTCT
Proportion of infants with HIV infection
Measured: 72 weeks postpartum
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2017
- Study start22 Jan 2018
- Primary completion20 Oct 2020
- Study completion5 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HIV-1-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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- An open-label, multi-centre randomised controlled trial
- Masking
- None (open label)
- Enrolment
- 268 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Liverpool
- Sponsor type
- University, hospital or other
- Collaborators
- UNITAID, University of Cape Town, Liverpool School of Tropical Medicine, Infectious Diseases Institute, Uganda, Radboud University Medical Center
- Responsible party
- Sponsor
- Investigators
- Saye H Khoo, Study chair, University of Liverpool
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03249181
- Sponsor's protocol ID
- DolPHIN-2
- Acronym
- DolPHIN-2
- Status last verified
- Nov 2023
- First submitted
- 28 Jul 2017
- Last updated
- 21 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kiiza D, Rostami-Hochaghan D, Alhassan Y, Seden K, Reynolds H, Kaboggoza JP, Taegtmeyer M, Chen T, Challenger E, Malaba T, Wang D, Else L, Hern F, Sharp J, Neary M, Dilly Penchala S, Waitt C, Orrell C, Colbers A, Myer L, Owen A, Rannard S, Khoo S, Lamorde M. Clinical, pharmacological, and qualitative characterization of drug-drug interactions in pregnant women initiating HIV therapy in Sub-Saharan Africa. J Antimicrob Chemother. 2024 Sep 3;79(9):2334-2342. doi: 10.1093/jac/dkae232.
PubMed 38997229Malaba TR, Nakatudde I, Kintu K, Colbers A, Chen T, Reynolds H, Read L, Read J, Stemmet LA, Mrubata M, Byrne K, Seden K, Twimukye A, Theunissen H, Hodel EM, Chiong J, Hu NC, Burger D, Wang D, Byamugisha J, Alhassan Y, Bokako S, Waitt C, Taegtmeyer M, Orrell C, Lamorde M, Myer L, Khoo S; DolPHIN-2 Study Group. 72 weeks post-partum follow-up of dolutegravir versus efavirenz initiated in late pregnancy (DolPHIN-2): an open-label, randomised controlled study. Lancet HIV. 2022 Aug;9(8):e534-e543. doi: 10.1016/S2352-3018(22)00173-4.
PubMed 35905752Ochanda PN, Lamorde M, Kintu K, Wang D, Chen T, Malaba T, Myer L, Waitt C, Reynolds H, Khoo S. A randomized comparison of health-related quality of life outcomes of dolutegravir versus efavirenz-based antiretroviral treatment initiated in the third trimester of pregnancy. AIDS Res Ther. 2022 Jun 7;19(1):24. doi: 10.1186/s12981-022-00446-3.
PubMed 35672853Kintu K, Malaba TR, Nakibuka J, Papamichael C, Colbers A, Byrne K, Seden K, Hodel EM, Chen T, Twimukye A, Byamugisha J, Reynolds H, Watson V, Burger D, Wang D, Waitt C, Taegtmeyer M, Orrell C, Lamorde M, Myer L, Khoo S; DolPHIN-2 Study Group. Dolutegravir versus efavirenz in women starting HIV therapy in late pregnancy (DolPHIN-2): an open-label, randomised controlled trial. Lancet HIV. 2020 May;7(5):e332-e339. doi: 10.1016/S2352-3018(20)30050-3.
PubMed 32386721
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dolutegravir in Pregnant HIV Mothers and Their Neonates
- ClinicalTrials.gov ID
- NCT03249181
- Acronym / sponsor ID
- DolPHIN-2 / DolPHIN-2
- Conditions
- HIV-1-infection, Pregnancy Related
- Keywords
- MTCT, Antiretroviral, Pregnancy, Africa
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 268 participants (actual)
- Lead sponsor
- University of LiverpoolUniversity, hospital or other
- Collaborators
- UNITAID, University of Cape Town, Liverpool School of Tropical Medicine, Infectious Diseases Institute, Uganda, Radboud University Medical Center
- Study start
- 22 Jan 2018 (actual)
- Primary completion
- 20 Oct 2020 (actual)
- Study completion
- 5 Sep 2023 (actual)
- First posted
- 15 Aug 2017 (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.
To evaluate dolutegravir (DTG) efficacy in women who present with untreated HIV in late pregnancy.
An open-label, multi-centre randomised controlled trial of DTG vs efavirenz-based regimens for women commencing cART in late pregnancy. HIV positive pregnant women presenting with untreated HIV infection in late (≥28 weeks gestation) pregnancy will be randomised 1:1 to receive DTG (50mg once daily) + 2 nucleoside reverse transcriptase inhibitors (NRTIs) or EFV + 2 NRTIs (SoC)
Detailed description
This is an open-label, randomised controlled trial of DTG versus EFV -based regimens for 250 women commencing cART in late pregnancy, randomised 1:1 to DTG vs EFV-based cART. The purpose of this study is to inform treatment guidelines and for the first time specifically address the treatment needs of this group of women- hence the trial is powered for superiority over EFV. The primary endpoints is maternal VL at delivery, with secondary endpoints including safety and tolerability of DTG in both mother and infant, VL decline in breast milk, development of drug resistance, pharmacokinetics of DTG in mother-infant pairs, pharmacogenomics factors relating to efficacy or toxicity of DTG, and MTCT of HIV up to 72 weeks postpartum. Two sites have been selected - Infectious Diseases Institute, Makerere University, Kampala, Uganda and the University of Cape Town, South Africa - both have a strong track record of successfully delivering collaborative multidisciplinary research in PMTCT. Furthermore, health economics analysis to examine costs and cost-effectiveness of DTG in late-presenting pregnant women will be conducted
The desired outcome of this project is to establish high quality evidence and operational guidance for use of DTG in late pregnancy. Late-presenting HIV-infected pregnant women are an important, but neglected group of vulnerable individuals in whom a randomised controlled intervention of HIV treatment has never previously been undertaken. This work will be done in relationship with WHO and the Clinton Health Access Initiative to ensure successful delivery of the project objectives.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- An open-label, multi-centre randomised controlled trial
| Arm | Type | Receives |
|---|---|---|
| Dolutegravir | Experimental | Drug: DolutegravirDolutegravir group (DTG+2 NRTIs) - to make best comparison with standard of care, these NRTIs should be those recommended by national policy. Participants randomized to the study drug will be commenced on an antiretroviral regimen comprising DTG 50mg once daily in combination with 2 NRTIs |
| Standard of Care (EFV + 2 NRTI backbone) | Active comparator | Drug: Standard of Care (EFV + 2 NRTI backbone)Participants randomized to receive standard of care will receive the currently used antiretroviral regimens in keeping with national policy (EFV + 2NRTIs at both study sites). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Women aged 18 years or older
- Pregnant ( ≥28 weeks gestation by best available gestation estimation)
- Untreated HIV infection in late pregnancy
Key exclusion criteria (11 listed)
- Received any antiretroviral drugs in previous 12 months
- Ever received integrase inhibitors
- Previous documented failure of an NNRTI-containing ART regimen, previous EFV-associated toxicity or other history of ARV use that would preclude randomisation based on investigator judgement
- Serum haemoglobin <8.0 g/dl
- eGFR<50 ml/min*
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 |
|---|---|---|
| DolutegravirPatients randomized to the study drug will be commenced on an antiretroviral regimen comprising DTG 50mg once daily in combination with 2 NRTIs | Drug | Dolutegravir |
| Standard of Care (EFV + 2 NRTI backbone)Patients randomized to receive standard of care will receive the currently used antiretroviral regimens in keeping with national policy. | Drug | Standard of Care (EFV + 2 NRTI backbone) |
Primary outcome
HIV Viral Load at Delivery
Time frame: by delivery
<50 copies/ mL
5 secondary outcomes
Plasma viral load
Time frame: By delivery
Maternal viral load to 48 weeks
Time frame: 48 weeks postpartum
Maternal viral load to 72 weeks
Time frame: 72 weeks postpartum
Occurrence of MTCT
Time frame: 48 weeks postpartum
Occurrence of MTCT
Time frame: 72 weeks postpartum
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2025.
- Derived from this study: PubMed 38997229Kiiza D, Rostami-Hochaghan D, Alhassan Y, Seden K, Reynolds H, Kaboggoza JP, Taegtmeyer M, Chen T, Challenger E, Malaba T, Wang D, Else L, Hern F, Sharp J, Neary M, Dilly Penchala S, Waitt C, Orrell C, Colbers A, Myer L, Owen A, Rannard S, Khoo S, Lamorde M. Clinical, pharmacological, and qualitative characterization of drug-drug interactions in pregnant women initiating HIV therapy in Sub-Saharan Africa. J Antimicrob Chemother. 2024 Sep 3;79(9):2334-2342. doi: 10.1093/jac/dkae232.
- Derived from this study: PubMed 35905752Malaba TR, Nakatudde I, Kintu K, Colbers A, Chen T, Reynolds H, Read L, Read J, Stemmet LA, Mrubata M, Byrne K, Seden K, Twimukye A, Theunissen H, Hodel EM, Chiong J, Hu NC, Burger D, Wang D, Byamugisha J, Alhassan Y, Bokako S, Waitt C, Taegtmeyer M, Orrell C, Lamorde M, Myer L, Khoo S; DolPHIN-2 Study Group. 72 weeks post-partum follow-up of dolutegravir versus efavirenz initiated in late pregnancy (DolPHIN-2): an open-label, randomised controlled study. Lancet HIV. 2022 Aug;9(8):e534-e543. doi: 10.1016/S2352-3018(22)00173-4.
- Derived from this study: PubMed 35672853Ochanda PN, Lamorde M, Kintu K, Wang D, Chen T, Malaba T, Myer L, Waitt C, Reynolds H, Khoo S. A randomized comparison of health-related quality of life outcomes of dolutegravir versus efavirenz-based antiretroviral treatment initiated in the third trimester of pregnancy. AIDS Res Ther. 2022 Jun 7;19(1):24. doi: 10.1186/s12981-022-00446-3.
- Derived from this study: PubMed 32386721Kintu K, Malaba TR, Nakibuka J, Papamichael C, Colbers A, Byrne K, Seden K, Hodel EM, Chen T, Twimukye A, Byamugisha J, Reynolds H, Watson V, Burger D, Wang D, Waitt C, Taegtmeyer M, Orrell C, Lamorde M, Myer L, Khoo S; DolPHIN-2 Study Group. Dolutegravir versus efavirenz in women starting HIV therapy in late pregnancy (DolPHIN-2): an open-label, randomised controlled trial. Lancet HIV. 2020 May;7(5):e332-e339. doi: 10.1016/S2352-3018(20)30050-3.
- Individual participant dataSharing planned: No
Related trials for HIV-1-infection
RecruitingObservational study
Cohort of Women Living With HIV-1 and Receiving Bictegravir/Emtricitabine/Tenofovir Alafenamide
HIV (Human Immunodeficiency Virus), Pregnancy
RecruitingPhase 4
A Study to Provide Continued Access to Study Drug to Children and Adolescents Who Have Completed Clinical Studies Involving Gilead HIV Treatments
HIV-1-infection
RecruitingObservational study
Leukapheresis Procedures to Obtain Plasma and Lymphocytes for Research Studies on Antiretroviral Naive HIV-1 Research Participants
HIV
Active, not recruitingPhase 3
Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With Biktarvy
HIV-1-infection
Active, not recruitingPhase 2/3
Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With a Complicated Regimen (ARTISTRY-1)
HIV-1-infection
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.
Saye H Khoo study chair
University of Liverpool
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dolutegravir in people with HIV-1-infection and Pregnancy Related, run by University of Liverpool at 2 sites in 2 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 5 inclusion and 11 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 21 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Africa, Uganda. 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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
HIV Viral Load at Delivery (time frame: by delivery). 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 NCT03249181, which also lists 4 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 21 Feb 2025.