CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: A rapid well-coordinated response ensured prompt communication of the DTG safety warning. Women made informed decisions with most opting to stay on DTG however effective contraception uptake was low. While a patient-centered approach was feasible in this clinic, ongoing monitoring for DTG pregnancy exposures is needed. 749 SERUM FOLATE AND BIRTH OUTCOMES: DTG VS EFV TRIAL EVIDENCE IN SOUTH AFRICA Nomathemba C. Chandiwana 1 , Andrew Hill 2 , Matthew Chersich 1 , Ellisha Maharaj 1 , Willem D. Venter 1 , Godspower Akpomiemie 1 , Celicia Serenata 1 , Lee Fairlie 1 , Simiso Sokhela 1 , Masebola Masenya 1 , Michelle A. Moorhouse 1 1 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, 2 University of Liverpool, Liverpool, UK Background: Dolutegravir (DTG) exposure was associated with a 5.4 fold higher risk of neural tube defects (NTDs) in the Botswana Tsepamo study. The mechanism underlying this potential association is unknown. Potentially, effects of DTG on folate metabolism, especially a lowering of levels, could account for these findings. We hypothesized that antiretroviral regimen could affect serum folate concentrations, and evaluated this in the ongoing South African ADVANCE trial (NCT03122262). Methods: In ADVANCE, 1053 treatment-naïve patients were randomised to start treatment with DTG-tenofovir alafenamide fumarate-emtricitabine (DTG-TAF-FTC), dolutegravir-tenofovir-emtricitabine (DTG-TDF-FTC) or efavirenz-tenofovir-emtricitabine (EFV-TDF-FTC). Preconception serum folate concentrations were measured in a subcohort (n=486) of female participants at weeks 0, 12 and 24 after enrolment. We compared changes in mean serum folate concentrations and the occurrence of marginal serum folate deficiency (<14.0 nmol/L) between study groups. We also describe birth outcomes in women who became pregnant during the trial. These women were on ART at conception, had a gestational age assessment (ultrasound and date of last menstrual period) and congenital foetal anomaly screen. Results: Mean serum folate concentrations were balanced across the treatment arms at baseline (Table 1). However, at weeks 12 and 24, mean serum folate was lower in women on EFV-TDF-FTC (p<0.001), and 30% of these women had marginal serum folate deficiency, compared to 13.7% in the DTG-TDF-FTC arm, and 5.4% in the DTG-TAF-FTC group (p<0.001) at week 24. No declines in serum folate concentrations in either DTG arms were noted. To date, 59 women have become pregnant; 19 in DTG-TAF-FTC; 20 on DTG-TDF-FTC; and 20 on EFV-TDF-FTC. Among pregnant women, those in the EFV-TDF-FTC arm had lower mean serum folate concentrations at week 12 (p<0.001) and differences were detected in marginal folate deficiency at week 24. There have been 16 live births; 1 infant death; 1 spontaneous abortion; 2 congenital anomalies (naevus flammeus and umbilical hernia), and 19 elective terminations, and 23 pregnancies are ongoing. Conclusion: In this randomised study, first-line treatment with EFV-TDF-FTC was associated with decline in folate over 24 weeks and with significantly lower serum folate concentrations than in women treated with DTG-TDF-FTC or DTG- TAF-FTC. DTG does not appear to alter folate metabolism, but effects of EFV on folate raise important concerns.

750 FETAL BIOMETRY SIMILAR WITH DOLUTEGRAVIR OR EFAVIRENZ EXPOSURE Gosego Masasa 1 , Kathleen M. Powis 2 , Samuel W. Kgole 1 , Keolebogile N. Mmasa 1 , Justine Legbedze 3 , Shan Sun 3 , Terence Mohammed 1 , Coulson Kgathi 1 , Joseph Makhema 1 , Francis Banda 4 , Mitchell Geffner 5 , Lynn M. Yee 6 , Lisa B. Haddad 7 , Elaine J. Abrams 8 , Jennifer Jao 6 1 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 2 Harvard University, Boston, MA, USA, 3 Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA, 4 University of Botswana, Gaborone, Botswana, 5 University of Southern California, Los Angeles, CA, USA, 6 Northwestern University, Chicago, IL, USA, 7 Emory University, Atlanta, GA, USA, 8 ICAP at Columbia University, New York, NY, USA Background: Pregnant women living with HIV (PWLHIV) are increasingly receiving dolutegravir (DTG) worldwide and in Botswana. Few studies have assessed fetal biometry in PWLHIV on DTG-based antiretroviral therapy (ART). Methods: We evaluated fetal biometry via ultrasound in PWLHIV and HIV-uninfected (HIV-U) pregnant women enrolled in the Tshilo Dikotla cohort in Botswana. PWLHIV enrolled between 16-36 weeks gestational age (GA) and received tenofovir + emtricitabine and either DTG or efavirenz (EFV). Pregnancies with multiple gestations or ending in fetal demise were excluded. Head circumference (HCZ), biparietal diameter (BPDZ), abdominal circumference (ACZ), and femur length (FLZ) Z scores were calculated using Intergrowth-21st references. Linear regression models were fit to assess the association of in utero HIV/ART exposure with each fetal biometric Z score, and among PWLHIV, the association of DTG vs EFV exposure with fetal biometry. Results: Of 435 pregnant women, 176 received DTG-based ART, 92 efavirenz (EFV)-based ART, and 167 were HIV-U. PWLHIV were older (28.9 vs 24.5 years, p=<0.01) higher in gravidity (3 vs 1, p<0.01), and less likely to have completed tertiary education (9.3% vs 31.1%, p<0.01) than HIV-U women. GA at ultrasound was higher in PWLHIV than HIV-U women (28 vs 26 weeks, p=0.01). Among PWLHIV, women on DTG were younger (28.2 vs 30.5 years, p=0.01) with shorter ART duration prior to ultrasound (15.3 vs 27.6 weeks, p<0.01) than those on EFV. In unadjusted analyses, median HCZ, BPDZ, ACZ, and FLZ did not differ between fetuses of PWLHIV vs HIV-U women (-0.30 vs -0.26, p=0.15; 0.09 vs 0.07, p=0.22; 0.00 vs 0.00, p=0.57 and 1.45 vs 1.24, p=0.22 respectively). This relationship persisted after adjusting for maternal age, height, education level, gravidity and alcohol use in pregnancy. There were no differences in fetal biometry between fetuses exposed to DTG vs EFV (HCZ: -0.39 vs -0.62, p=0.15, BPD: 0.14 vs 0.34, p=0.27, ACZ: 0.31 vs 0.34, p=0.15, FLZ: 1.42 vs 1.49, p=0.24). This relationship remained after adjusting for the same variables above as well as CD4 count. (Table) Conclusion: In this small Botswana cohort, there does not appear to be a substantial association between in utero HIV/ARV exposure and fetal biometry or between in utero DTG vs EFV exposure and fetal biometry. While these results are reassuring and support continued use of these regimens in pregnancy, larger studies with serial ultrasounds are needed to validate these findings.

Poster Abstracts

751 SIMILAR BIRTH ANTHROPOMETRICS WITH IN UTERO EXPOSURE TO DOLUTEGRAVIR OR EFAVIRENZ Samuel W. Kgole 1 , Jennifer Jao 2 , Shan Sun 3 , Keolebogile N. Mmasa 1 , Gosego Masasa 1 , Justine Legbedze 3 , Sikhulile Moyo 1 , Coulson Kgathi 1 , Joseph Makhema 1 , Francis Banda 4 , Mitchell Geffner 5 , Mariana Gerschenson 6 , Irwin J. Kurland 7 , Elaine J. Abrams 8 , Kathleen M. Powis 9

CROI 2019 289