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DolPHIN-1: DOLUTEGRAVIR VS EFAVIRENZ WHEN INITIATING TREATMENT IN LATE PREGNANCY
Catriona Waitt1, Stephen I. Walimbwa2, Catherine Orrell3, Mohammed Lamorde2, Christie Heiberg3, Ushma Mehta4, Julian P. Kaboggoza2, Julie Anne Coombs3, Josaphat Byagumisha2, Alieu Amara1, Thoko Malaba4, Laura Else1, Landon Myer4, Saye Khoo1
1University of Liverpool, Liverpool, UK,2Infectious Disease Institute, Kampala, Uganda,3Desmond Tutu HIV Foundation, Cape Town, South Africa,4University of Cape Town, Cape Town, South Africa
Initiation of ART in the 3rd trimester of pregnancy is associated with adverse outcomes and increased vertical transmission of HIV. DolPHIN-1 (NCT02245022) is a randomised trial of EFV or DTG plus 2NRTIs in pregnant women initiating ART between 28-36w of gestation in Uganda and South Africa. This scheduled interim review was undertaken after the first 16 mothers delivered. The primary endpoint was pharmacokinetics (PK) of DTG; secondary endpoints included VL responses, safety and tolerability of DTG, and placental/breast milk transfer of DTG.
Eligible, consenting mothers were randomised 1:1 to EFV or DTG arms. To comply with national guidelines, EFV-containing ART was initiated on the day of referral. Subjects randomized to DTG were switched from EFV within 7 days. Demographic, serial clinical and laboratory data and birth outcome data were collected. VL responses were collected at baseline, 14d and 28d, as well as post-partum. All infants were exclusively breastfed. Intensive PK sampling (0-24h) was performed at 14d on DTG, and 2w post-partum.
Of the 16 subjects who delivered, 8 each received DTG or EFV. Median baseline VL was log 4.15 (range 2.43-6.07) copies/mL and similar between arms. PK data in 3rd trimester are shown (Table 1). The proportion of VL reported as less than 50 copies or undetectable at 2 weeks and at 4 weeks of therapy was 5/8 and 4/8 in mothers on DTG, and 1/5 and 2/7 in mothers on EFV, respectively. At 2 weeks post-partum 5/6 and 4/7 mothers on DTG, and EFV respectively had VL less than 50 copies. Two mothers in the DTG arm were withdrawn for virological failure; the first had no detectable drug in plasma and was non-adherent, the second had evidence of 3 class drug resistance (RT and protease mutations); no women were withdrawn from the EFV arm. Both regimens were well-tolerated. A total of 4 SAE's were reported: DTG arm: 1 G3 elevation in liver function tests (possibly drug related, concomitant herbal use recorded) with stillbirth in the same mother (tight cord around the neck, deemed unrelated to study drug); EFV arm: 1 G3 hypertension, 1 baby with polydactyly.
This planned interim assessment suggests DTG appears to be well-tolerated and effective when initiated in late pregnancy. PK findings are consistent with other studies and suggest that dosing of DTG at 50mg once-daily appears appropriate in third trimester. The study continues, with a definitive efficacy study (DolPHIN-2) in development.