Dolutegravir in Pregnant HIV Mothers and Their Neonates

NCT03249181 | Completed Phase 3 DMC

• 1 other identifier: DolPHIN-2
• Study Type: interventional
• Target: 268
• Locations: 2 countries
• Sites: 2

Brief 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. 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)

Conditions

HIV-1-infection; Pregnancy Related

Keywords

MTCT; Antiretroviral; Pregnancy; Africa

Outcome Measures

Primary Outcomes (1)

• HIV Viral Load at Delivery

  \<50 copies/ mL

  by delivery

Secondary Outcomes (5)

• Plasma viral load

  By delivery

• Maternal viral load to 48 weeks

  48 weeks postpartum

• Maternal viral load to 72 weeks

  72 weeks postpartum

• Occurrence of MTCT

  48 weeks postpartum

• Occurrence of MTCT

  72 weeks postpartum

Other Outcomes (18)

• Drug toxicities as defined by DAIDS criteria

  Each study visit up to 72 weeks postpartum

• Drug toxicities as defined by DAIDS criteria

  Each study visit up to 72 weeks postpartum

• Drug toxicities as defined by DAIDS criteria

  Each study visit up to 72 weeks postpartum

Study Arms (2)

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

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).

Drug: Standard of Care (EFV + 2 NRTI backbone)

Interventions

Dolutegravir DRUG

Patients randomized to the study drug will be commenced on an antiretroviral regimen comprising DTG 50mg once daily in combination with 2 NRTIs

Dolutegravir

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.

Standard of Care (EFV + 2 NRTI backbone)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• University of Liverpool: lead
• UNITAID: collaborator
• University of Cape Town: collaborator
• Liverpool School of Tropical Medicine: collaborator
• Infectious Diseases Institute, Uganda: collaborator
• Radboud University Medical Center: collaborator

Study Sites (2)

University of Cape Town

Cape Town, Western Cape, South Africa

Location

Infectious Diseases Institute

Kampala, Uganda

Location

Related Publications (4)

• 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.

  PMID: 38997229 DERIVED

• Malaba 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.

  PMID: 35905752 DERIVED

• Ochanda 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.

  PMID: 35672853 DERIVED

• Kintu 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.

  PMID: 32386721 DERIVED

MeSH Terms

Interventions

dolutegravir; Standard of Care; efavirenz

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Saye H Khoo

  University of Liverpool

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: An open-label, multi-centre randomised controlled trial

Study Record Dates

• First Submitted: July 28, 2017
• First Posted: August 15, 2017
• Study Start: January 22, 2018
• Primary Completion: October 20, 2020
• Study Completion: September 5, 2023
• Last Updated: February 21, 2025

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1); ZA (1)