CompletedPhase 2/3

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

South Africa, Uganda60 participantsStarted 2017-03-14

Plain-language 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

Who can participate

Age range18 Years

SexFEMALE

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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

What they're measuring

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

Timeframe: In 3rd trimester and 2 weeks postpartum

Cmax of Dolutegravir

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

Trough Concentration

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

Trial details

NCT IDNCT02245022

SponsorUniversity of Liverpool

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2018-12-06

Results submitted2022-12-13

View on ClinicalTrials.gov More HIV trials