CROI 2019 Abstract eBook

Abstract eBook

Oral Abstracts

Catriona Waitt 5 , Catherine Orrell 2 , Mohammed Lamorde 1 , Landon Myer 2 , Saye Khoo 5 , for the DolPHIN-2 Study Group 1 Infectious Disease Institute, Kampala, Uganda, 2 University of Cape Town, Cape Town, South Africa, 3 Liverpool School of Tropical Medicine, Liverpool, UK, 4 Radboud University, Nijmegen, Netherlands, 5 University of Liverpool, Liverpool, UK Background: ART initiation late in pregnancy is associated with failure to achieve viral suppression by delivery and increased MTCT. Methods: DolPHIN-2 (NCT03249181) is an open label trial, randomising (1:1) pregnant women from Uganda and South Africa initiating ART from 28w gestation to dolutegravir (DTG) vs efavirenz (EFV) plus 2NRTIs. Viral load (VL) was measured at baseline, 1w and 4w after initiation, then at 36w gestation and delivery, and 6w post-partum (PP). The primary endpoint was VL<50 cps/mL at delivery (measured up to 14d PP) for efficacy, and occurrence of drug toxicity in mothers and infants. Here we report on all primary trial endpoints through delivery. Results: All 268 mothers randomised were included in safety, and 237 (122 DTG, 115 EFV) in efficacy analyses by ITT. At enrolment there were no differences between DTG vs EFV in median gestation (31w), VL (log 10 4.4 vs 4.5 cps/mL), CD4 count (464 vs 412 cells/µL) or other characteristics. The median duration of ART at delivery was 52 vs 59 days (range 0 – 133 days). VL<50 cps/mL at delivery was significantly higher with DTG (90/122, 74%) vs EFV (49/115, 43%); adjusted risk ratio (RR) and 95% CI, 1.66 (1.32-2.09) (Figure). This trend was consistent across subgroups of baseline VL; CD4 cell count; gestation at initiation; and other characteristics. VL<1000 cps/mL at delivery was also more likely in women on DTG vs EFV (93% vs 83%); RR, 1.11 (1.00-1.23). DTG was well-tolerated in pregnancy with no differences with EFV in frequency or organ class of severe adverse events. There were no significant differences between DTG and EFV arms in median gestational age at delivery (39.9w for both arms), or births at <34w (4.76% vs 5.13%) and <37w (16.67% vs 15.38%) gestation respectively. There were 4 stillbirths (aetiological factors under investigation), all in the DTG arm. Of 270 live births, congenital anomalies (excluding umbilical hernias and birthmarks) were reported in 17 infants (DTG 8, EFV 9) up to 6w of age; no neural tube defects were observed. There were 7 infant deaths (DTG 4, EFV 3). Three cases of MTCT were detected at birth, all from the DTG arm, and considered likely to be in-utero transmissions. Conclusion: DTG is well-tolerated and achieves more rapid virological suppression before delivery compared to EFV when initiated in late pregnancy. Late presentation in pregnancy is associated with poor outcomes despite ART and regardless of arm.

Mmbaga 8 , Jose Henrique S. Pilotto 9 , Avy Violari 10 , Sinart Prommas 11 , Esau Joao 7 , for the NICHD P1081 Protocol Team 1 Boston University, Boston, MA, USA, 2 Harvard T.H. Chan School of Public Health, Boston, MA, USA, 3 Seattle Children’s Research Institute, Seattle, WA, USA, 4 National Institute of Child Health and Human Development, Bethesda, MD, USA, 5 United States Agency for International Development, Washington, DC, USA, 6 University of California San Diego, La Jolla, CA, USA, 7 Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil, 8 Kilimanjaro Christian Medical Centre, Moshi, Tanzania, 9 Hospital Geral de Nova Iguaçu, Rio de Janeiro, Brazil, 10 University of the Witwatersrand, Johannesburg, South Africa, 11 Bhumibol Adulyadej Hospital, Bangkok, Thailand Background: There are no randomized trial data comparing the efficacy and safety of antiretroviral therapy (ART) containing an integrase inhibitor with efavirenz (EFV) when initiated during pregnancy. Methods: NICHD P1081 is a Phase IV multicenter, randomized, open-label trial comparing HIV virologic response (plasma HIV viral load <200 copies/ml near delivery), tolerability (remaining on study drug through delivery), and safety (maternal and infant adverse event (AE) ≥grade 3) of ART when initiated during pregnancy. ART-naïve pregnant women with HIV were randomized to raltegravir (RAL)- or EFV-based ART through delivery. Enrollment began in Sept 2013 for women 28 to <37 weeks (wks) gestation (gest), was expanded to 20 to <37 wks gest after 22%were enrolled, and was completed in Feb 2018. Women and their infants were followed through 24 wks post-delivery. The randomization and primary statistical comparisons were stratified by gest age at entry. Results: 408 pregnant women (206 RAL arm, 202 EFV arm) were enrolled at 19 sites in South America (n=210), Africa (n=144), Thailand (n=47) and the US (n=7), 205 (50%) at 20 to <28 wks and 203 (50%) at 28 to <37 wks. In the primary efficacy subgroup (n=307 with no HIV genotypic resistance to study ART at entry), a larger proportion of women in the RAL arm vs. EFV arm had delivery viral load <200 copies/mL (94% vs. 84%; p=.001), mainly among those enrolled at ≥28 wks gest (interaction p=.04); results were similar after including women with HIV genotypic resistance to study ART at entry (n=362, Table, interaction p=.06). Viral load decline was greater in RAL arm at study wks 2, 4 and 6 (Wilcoxon p<.05). Both regimens were well tolerated (Table). A larger proportion of RAL armwomen achieved a rapid, sustained viral load reduction while staying on study drug until delivery, mainly by achieving a rapid viral load decline by study wk 2 (Table). There were no significant differences in occurrence of AE ≥grade 3 among women or infants, stillbirth, or preterm birth (Table). One RAL infant and 4 EFV infants were HIV infected (Fisher exact p>.05). Conclusion: Both regimens were well tolerated in women initiating ART during pregnancy. Viral load reduction with RAL-ART was faster leading to more women with delivery viral load <200 copies/mL. These data from the first large randomized trial comparing an integrase inhibitor with EFV-ART initiated during pregnancy support the use of RAL-ART during pregnancy, especially for women starting ART late in gestation.

Oral Abstracts

41 MATERNAL HBV VIREMIA IS ASSOCIATED WITH ADVERSE INFANT OUTCOMES IN HIV/HBV WOMEN

Debika Bhattacharya 1 , Rong Guo 1 , Chi-hong Tseng 1 , Lynda Emel 2 , Ren Sun 1 , Shih-Hsin Chiu 1 , Lynda Stranix-Chibanda 3 , Tsungai Chipato 3 , Neaka Z. Mohtashemi 1 , Kenneth Kintu 4 , Karim P. Manji 5 , Dhayendre Moodley 6 , Chloe Thio 7 , Yvonne Maldonado 8 , Judith S. Currier 1 1 University of California Los Angeles, Los Angeles, CA, USA, 2 Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 3 University of Zimbabwe, Harare, Zimbabwe, 4 Makerere University–Johns Hopkins University Research Collaboration, Kampala, Uganda, 5 Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania, United Republic of, 6 University of KwaZulu-Natal, Durban, South Africa, 7 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 8 Stanford University, Stanford, CA, USA Background: HIV/HBV coinfection is common, yet there is little information on maternal and infant clinical outcomes. We assessed the prevalence of

40LB RCT OF DOLUTEGRAVIR VS EFAVIRENZ-BASED THERAPY INITIATED IN LATE PREGNANCY: DOLPHIN-2 Kenneth Kintu 1 , Thoko Malaba 2 , Jesca Nakibuka 1 , Christiana Papamichael 3 , Angela Colbers 4 , Kay Seden 5 , Victoria Watson 3 , Helen Reynolds 5 , Duolao Wang 3 ,

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CROI 2019