Safety and Pharmacokinetics of Dolutegravir in Pregnant HIV Mothers and Their Neonates: A Pilot Study

NCT02245022 | Completed Phase 2 Results DMC

• 1 other identifier: PK12
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 2

Brief Summary

Aim: To evaluate dolutegravir (DTG) pharmacokinetics in pregnant HIV-infected women Rationale: In developing countries many women present with a new HIV diagnosis in late pregnancy, and are at high risk of transmitting infection during delivery. Moreover, women may acquire NNRTI resistance from primary transmission, or use of nevirapine (NVP) in previous pregnancies. In these circumstances, DTG is likely to be more effective in reducing mother to child transmission of HIV than NNRTI-based regimens. Study design: HIV positive pregnant women presenting with untreated HIV infection in late (≥28 -36 weeks gestation) pregnancy will be randomised 1:1 to receive DTG (50mg once daily) or standard of care (nevirapine or efavirenz) + 2 NRTIs. PK (0-24h) profile will be sampled in third trimester and post-partum. Although this is primarily a PK study (and has been powered as such) randomisation is included to allow comparison of plasma HIV VL responses against standard of care (NVP or EFV) and is essential for evaluation of secondary endpoints of safety and efficacy of DTG in pregnancy. Number recruited N=30 per group

Conditions

HIV; Pregnancy

Keywords

HIV; Prevention of mother to child transmission; Africa; Uganda; Pharmacokinetics; Pregnancy; Breastfeeding

Outcome Measures

Primary Outcomes (3)

• AUC0-24 of DTG in Pregnant Women in Third Trimester and 2 Weeks Postpartum

  Rich PK with sampling at t0, 1, 2, 4, 6, 8 and 24 hours relative to drug dose

  In 3rd trimester and 2 weeks postpartum

• Cmax of Dolutegravir

  Maximum plasma concentration of dolutegravir in pregnancy vs postpartum

  After 2 weeks of starting dolutegravir, and again 2 weeks after delivery

• Trough Concentration

  Concentration at 24 hours after dose, immediately prior to next dose) of dolutegravir

  At 2 weeks after starting dolutegravir and again 2 weeks after delivery

Secondary Outcomes (9)

• Number of Participants Reporting Severe Adverse Events During Study Period

  From 7 days after start of treatment to 6 months postpartum

• Percentage of Women in Each Arm With VL < 50 Copies/mL, and <400 Copies/mL at Delivery

  At delivery

• Cord:Maternal Plasma DTG Ratio

  At delivery

• Maternal Plasma: Breastmilk DTG Ratio

  At 2 weeks postpartum, and 24 hours after final maternal dose

• Infant DTG Levels

  At maternal steady state (2 weeks postpartum) and at 1, 2 and 3 days after transfer to standard of care

Study Arms (2)

Dolutegravir 50mg od

EXPERIMENTAL

30 patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir)

Drug: Dolutegravir 50mg od

Standard of Care

ACTIVE COMPARATOR

Patients randomised to receive antiretroviral therapy as per Uganda national guidelines (Efavirenz 600mg od based plus Tenofovir 300mg od and Lamivudine 300mg od)

Drug: Standard of Care

Interventions

Dolutegravir 50mg od DRUG

Patients randomised to receive either Dolutegravir 50mg od or standard of care (Efavirenz 600mg od) plus Lamivudine 300mg od/ Tenofovir 300mg od

Also known as: Tivicay (ViiV Healthcare), GSK1349572

Dolutegravir 50mg od

Standard of Care DRUG

Patients are randomised 1:1 to receive either Dolutegravir 50mg once daily in combination with Lamivudine 300mg od and tenofovir 300mg od or standard of care (Efavirenz 600mg plus Lamivudine 300mg od and tenofovir 300mg od)

Also known as: Efavirenz 600mg od, Lamivudine 300mg od, Tenofovir 300mg od

Standard of Care

Eligibility Criteria

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

You may qualify if:

• Able to provide informed consent
• Willing to participate,
• Women age 18 years and above
• Pregnant
• Untreated HIV infection in late pregnancy at ≥28 - 36 weeks gestation

You may not qualify if:

• Received antiretroviral drugs in previous 6 months
• Ever received integrase inhibitors
• Serum haemoglobin \< 8.0 g/dl
• 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)
• eGFR \< 50ml/min
• Active Hepatitis B infection, history or clinical suspicion of unstable liver disease, or subjects with severe liver disease (Class C by Childs-Hugh criteria)
• Severe pre-eclampsia (e.g. HELLP), or other pregnancy related events such as renal or liver abnormalities (e.g. grade 2 or above proteinuria, elevation in serum creatinine (above 2.5 x ULN), total bilirubin ALT or AST)
• Paternal non-consent (where disclosure to male partner has been made)
• Clinical depression or clinical judgement suggests increased risk of suicidality

Sponsors & Collaborators

• University of Liverpool: lead
• ViiV Healthcare: collaborator
• Makerere University: collaborator

Study Sites (2)

Desmond Tutu HIV Foundation

Cape Town, Western Cape, South Africa

Location

Infectious Diseases Institute

Kampala, Uganda

Location

Related Publications (2)

• Dickinson L, Walimbwa S, Singh Y, Kaboggoza J, Kintu K, Sihlangu M, Coombs JA, Malaba TR, Byamugisha J, Pertinez H, Amara A, Gini J, Else L, Heiberg C, Hodel EM, Reynolds H, Myer L, Waitt C, Khoo S, Lamorde M, Orrell C; DolPHIN-1 Study Group. Infant Exposure to Dolutegravir Through Placental and Breast Milk Transfer: A Population Pharmacokinetic Analysis of DolPHIN-1. Clin Infect Dis. 2021 Sep 7;73(5):e1200-e1207. doi: 10.1093/cid/ciaa1861.

  PMID: 33346335 DERIVED

• Waitt C, Orrell C, Walimbwa S, Singh Y, Kintu K, Simmons B, Kaboggoza J, Sihlangu M, Coombs JA, Malaba T, Byamugisha J, Amara A, Gini J, Else L, Heiburg C, Hodel EM, Reynolds H, Mehta U, Byakika-Kibwika P, Hill A, Myer L, Lamorde M, Khoo S. Safety and pharmacokinetics of dolutegravir in pregnant mothers with HIV infection and their neonates: A randomised trial (DolPHIN-1 study). PLoS Med. 2019 Sep 20;16(9):e1002895. doi: 10.1371/journal.pmed.1002895. eCollection 2019 Sep.

  PMID: 31539371 DERIVED

MeSH Terms

Conditions

Breast Feeding

Interventions

dolutegravir; Standard of Care; efavirenz; Lamivudine; Tenofovir

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Catriona Waitt
• Organization: University of Liverpool

cwaitt@liverpool.ac.uk

0778288217

Study Officials

• Saye H Khoo, PhD, MBChB

  University of Liverpool

  PRINCIPAL INVESTIGATOR

• Mohammed Lamorde, PhD, MBChB

  Infectious Diseases Institute, Makerere University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Site sub-investigator

Study Record Dates

• First Submitted: September 12, 2014
• First Posted: September 19, 2014
• Study Start: March 14, 2017
• Primary Completion: December 6, 2018
• Study Completion: December 6, 2018
• Last Updated: September 4, 2025
• Results First Posted: September 4, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1); UG (1)