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Phase 3 N=60 Randomized Treatment

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

HIV · Pregnancy

Enrolled (actual)
60
Serious AEs
5.0%
Results posted
Sep 2025
Primary outcome: Primary: AUC0-24 of DTG in Pregnant Women in Third Trimester and 2 Weeks Postpartum — 35322; 40127 ng*h/mL

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Dolutegravir 50mg od (Drug); Standard of Care (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
Female
Sponsor
University of Liverpool
Primary completion
Dec 2018

Outcome Measures

OutcomeResultp-value
PRIMARY
AUC0-24 of DTG in Pregnant Women in Third Trimester and 2 Weeks Postpartum
35322; 40127
PRIMARY
Cmax of Dolutegravir
2534; 2899
PRIMARY
Trough Concentration
642; 777
SECONDARY
Number of Participants Reporting Severe Adverse Events During Study Period
2; 1
SECONDARY
Percentage of Women in Each Arm With VL < 50 Copies/mL, and <400 Copies/mL at Delivery
21; 12
SECONDARY
Cord:Maternal Plasma DTG Ratio
1.21
SECONDARY
Maternal Plasma: Breastmilk DTG Ratio
0.03
SECONDARY
Infant DTG Levels
66.7
SECONDARY
Number and Severity of Adverse Events and Laboratory Abnormalities
2; 0
SECONDARY
Percentage of Subjects Who Discontinue Treatment Due to Adverse Events
0; 0
SECONDARY
Percentage of Mother to Child Transmission of HIV
0; 0
SECONDARY
Pharmacogenomic Factors Influencing Transplacental and Breast Milk Transfer of Drug

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

Eligibility Criteria

Inclusion Criteria

  • 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

Exclusion Criteria

  • Received antiretroviral drugs in previous 6 months
  • Ever received integrase inhibitors
  • Serum haemoglobin 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02245022). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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