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

• Status: Completed
• Trial end date: 2018-12-06
• Target enrollment: 0
• Participant gender: Female

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

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Liverpool
• Collaborators: Makerere University; ViiV Healthcare
• Treatments: Dolutegravir; Efavirenz; Lamivudine; Tenofovir

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 < 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