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

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

Timeline

Start

2017-03-14

Primary completion

2018-12-06

Completion

2018-12-06

Publications

• 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.
• 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.

Drugs

Indications