CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

807 DolPHIN-1: DOLUTEGRAVIR VS EFAVIRENZ WHEN INITIATING TREATMENT IN LATE PREGNANCY

Catriona Waitt 1 , Stephen I. Walimbwa 2 , Catherine Orrell 3 , Mohammed Lamorde 2 , Christie Heiberg 3 , Ushma Mehta 4 , Julian P. Kaboggoza 2 , Julie Anne Coombs 3 , Josaphat Byagumisha 2 , Alieu Amara 1 , Thoko Malaba 4 , Laura Else 1 , Landon Myer 4 , Saye Khoo 1 1 University of Liverpool, Liverpool, UK, 2 Infectious Disease Institute, Kampala, Uganda, 3 Desmond Tutu HIV Foundation, Cape Town, South Africa, 4 University of Cape Town, Cape Town, South Africa Background: 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. Methods: 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. Results: 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 Two mothers in the DTG armwere withdrawn for virological failure; the first had no detectable drug in plasma and was non- adherent, the second had evidence of 3 class drug resistance (RT and protease mutations); no women were withdrawn from the EFV arm.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. Conclusion: 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.

806 RALTEGRAVIR IN PREGNANCY: PATTERNS OF USE AND BIRTH OUTCOMES IN THE UK AND IRELAND Rebecca Sconza , Virginia Rasi, Helen Peters, Mario Cortina-Borja, Claire Thorne UCL Great Ormond Street Institute of Child Health, London, UK Background: Raltegravir (RAL) is an HIV-1 integrase inhibitor known to rapidly reduce HIV RNA viral load (VL). RAL is often used in pregnancy to reduce risk of mother-to-child transmission, particularly for women presenting and/or diagnosed late in pregnancy. Methods: The National Study of HIV in Pregnancy and Childhood (NSHPC) conducts active surveillance of pregnancies in women living with HIV in the UK and Ireland. We describe trends in RAL use and outcomes among pregnancies resulting in a live- or stillbirth in 2008-16. Results: RAL was used in 709 (7%) of 10,144 reported pregnancies in 2008-16. RAL use increased steadily over time from 0.5% (13/2605) of pregnancies in 2008-09 to 14.4% (252/1747) in 2015-16 (p<0.001). Of RAL-exposed pregnancies, use at conception increased from 15% (2/13) in 2008-09 to 30% (76/252) in 2015-16. Of 265 pregnancies with late ART start in pregnancy due to late antenatal booking (>27 weeks), 68 (26%) received RAL overall, reaching 52% (15/29) in 2015-16. Of 709 pregnancies on RAL, 161 (23%) conceived on RAL (Group A), 137 (19%) conceived on ART but initiated RAL antenatally (Group B), and 411 (58%) initiated ART and RAL in pregnancy (Group C) (Table). Six pregnancies ended in stillbirth and there were 728 live-born infants (50 twins). Two-thirds (468/695) were in African-born women, 28% (195/709) in women with antenatal HIV diagnosis, and 4% (26/709) in women with perinatally- acquired HIV. In 44 RAL-exposed pregnancies, HIV diagnosis occurred in pregnancy and booking for antenatal care and initiation of ART were late; in these cases, RAL was started at a median 34 gestational weeks (IQR 32-37) and 56% (23/41) had VL >50 copies/ml at delivery (≤30 days). Twenty-one (3.1%) of 678 singleton RAL-exposed liveborn infants had a reported congenital abnormality, with a similar rate seen in unexposed infants (2.7%); 4.0% (7/174) of infants exposed in the first trimester had an abnormality versus 2.7% (13/490) of those exposed in second/third trimester (14 missing RAL start date) (p=0.36). Conclusion: RAL use is steadily increasing in pregnancy in UK/Ireland, particularly from before conception, but the group of pregnant women on RAL is heterogeneous. Half of pregnancies with late (third trimester) ART initiation received RAL in 2015-16, consistent with recommendations for RAL usage in pregnancy. Data on congenital abnormalities in RAL-exposed pregnancies are reassuring, but more work is needed to assess overall safety.

Poster Abstracts

808 DIPSTICKS PROTEINURIA TO PREDICT RENAL DYSFUNCTION IN HIV- INFECTED PREGNANT WOMEN Mwangelwa Mubiana-Mbewe 1 , Bridget Mugisa 2 , Bernadette Ngeno 3 , Paul R. Young 3 , Jillian L. Kadota 4 , Benjamin H. Chi 5 , Charles B. Holmes 6 , Michael Vinikoor 7 1 Centre for Infectious Disease Research in Zambia, Lusaka, Zambia, 2 CDC, Lusaka, Zambia, 3 CDC, Atlanta, GA, USA, 4 Center for Infectious Disease Research in Zambia, Lusaka, Zambia, 5 University of North Carolina Chapel Hill, Chapel Hill, NC, USA, 6 Johns Hopkins University, Baltimore, MD, USA, 7 University of Alabama at Birmingham, Birmingham, AL, USA Background: The Zambian national HIV guidelines recommend urinalysis to detect proteinuria as a baseline screening test for renal insufficiency among HIV-infected pregnant women initiating tenofovir-based first-line antiretroviral therapy (ART). To date, few data are available to evaluate the sensitivity of urine dipsticks for renal dysfunction.

CROI 2018 304