CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

710

Intracellular Sofosbuvir Concentrations in Pregnant Women With Hepatitis C Virus Catherine A Chappell 1 , Kristina M. Brooks 2 , Jennifer J. Kiser 2 , Ingrid S. Macio 3 , Leslie A. Meyn 3 , Kyung-min Kwon 4 , Cathleen Letterio 4 , Sarjita Naik 4 , Bruce Kreter 4 , Sharon L. Hillier 1 1 University of Pittsburgh, Pittsburgh, PA, USA, 2 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 3 Magee–Womens Research Institute, Pittsburgh, PA, USA, 4 Gilead Sciences, Inc, Foster City, CA, USA Background: Treatment of hepatitis C virus (HCV) during pregnancy could cure maternal HCV during antenatal care engagement and prevent perinatal HCV transmission. We previously showed plasma sofosbuvir (SOF) exposures were 38% higher during pregnancy, whereas as the inactive metabolite of SOF (007) was 38% lower compared to non-pregnant women. SOF is converted into its active form, 007-triphosphate (007-TP), within cells and can be used as a surrogate of activation in other tissue types and adherence markers. Our objectives were to describe 007-TP concentrations in dried blood spots (DBS) and peripheral blood mononuclear cells (PBMCs) during pregnancy. Methods: In this open-label, phase 1 study, HIV-negative pregnant women with chronic HCV infection were enrolled between 23-25 weeks' gestation and were treated with SOF 400mg/velpatasvir (VEL) 100mg daily for 12 weeks. DBS and PBMCs were collected pre-dose at 3, 6 and 9 weeks of treatment. 007-TP in DBS (1x7mm punch) and PBMCs (normalized to 10 6 cells) were measured using validated LC/MS-MS methods. Results were summarized using descriptive statistics. Comparisons to 007-TP concentrations measured in non pregnant persons with HCV and adherence monitoring were also performed (NCT02573376). Results: Data were available in 10 pregnant people (9 white, 1 Black; median (range) age 31 (25-29) years and weight 75.5 (64.6-102.3) kg). Median (range) serum creatinine, glomerular filtration rate, and hematocrit were 0.5 (0.4 0.6) mg/dL, 126.1 (122.3-140.8) mL/min/1.73 m 2 , and 36.1% (33.2-37.8%), respectively. Geometric mean (95% CI) 007-TP in DBS were 340 (287, 403), 340 (278, 418), and 356 (275, 461) fmol/punch at weeks 3, 6, and 9 (A). Geometric mean (95% CI) 007-TP in PBMCs were 2111 (1096, 4066), 2808 (1559, 5058), and 2212 (1267, 3864) fmol/10 6 cells at weeks 3, 6, and 9 (B). In comparison to non-pregnant adults (n=58), 007-TP concentrations in PBMCs were comparable or higher, whereas 007-TP in DBS were ~50% lower in pregnancy. Conclusion: Though 007-TP concentrations were altered in pregnancy, the efficacy of SOF/VEL in this trial was unaffected (100% of those that attended the final maternal visit were cured [n=8]). The decreased concentrations in DBS could be due in part to physiologic hemodilution of pregnancy. Thus, if DBS samples were used to measure adherence in trials, they would need to be adjusted. An international, multicenter trial evaluating the safety and efficacy of SOF/VEL treatment in pregnancy is underway (NCT05140941).

completed treatment though this was not statistically significant (Δ = 7%, p=0.09) (Table). Among participants <40 years or with recent IDU, treatment initiation did not differ between arms (p=0.75). Conclusion: Among ED patients with untreated HCV, early follow-up suggests that LN in addition to CR is superior to CR-alone for initiating HCV treatment, but additional follow-up is needed to better understand the effect of a linkage navigator on the downstream elements of the HCV continuum, including treatment completion and cure, and cost effectiveness of employing a navigator. Even with a navigator, linkage rates were low suggesting new approaches to HCV treatment initiation are needed.

709

Peripartum Linkage to Care in Hepatitis C: Infant Testing and Maternal Treatment John Cafardi 1 , Hong Lin 2 , Lana Lange 1 , Lacey Kelley 3 , Kelly Lemon 3 , Elisabeth Odegard 2 , Heidi L. Meeds 2 , Jason T. Blackard 2 , Judiith Feinberg 3 1 The Christ Hospital, Cincinnati, OH, USA, 2 University of Cincinnati, Cincinnati, OH, USA, 3 West Virginia Clinical and Translational Science Institute, Morgantown, WV, USA Background: There is an increase in hepatitis C virus (HCV) infection due to injection drug use and poor access to care. Ohio had an 89% increase in HCV in women of childbearing age between 2010 and 2015 with children born to HCV infected women increased 68%. HCV testing of infants is recommended at 18 months of age but testing and follow-up are poor. Between 2011-2013 only 16% of eligible infants in Philadelphia received appropriate testing. Maternal linkage to care and treatment are also inadequate, with rates commonly less than 20% Improvements in linkage to care as well as testing and treatment are needed. Methods: Fifty-four pregnant women with chronic HCV infection were recruited from outpatient clinics in Ohio and West Virginia. Eligible participants were 18 or older with singleton pregnancy up to 36 weeks. Hepatitis B coinfection, active drug use and severe medical comorbidities were exclusionary. After written informed consent, participants were educated about HCV and were seen up to seven times (enrollment, 36 weeks gestation, and 12, 24, 36 and 48 weeks postpartum). All participants were offered once daily sofosbuvir-velpatasvir for 84 days at 24 weeks postpartum. Cessation of breastfeeding and negative pregnancy test were confirmed prior to treatment. Three maternal blood samples were collected (36 weeks as well as at 28- and 48-weeks postpartum) while infant blood samples were collected at 12, 24, and 48 weeks postpartum. All maternal and infant testing was performed simultaneously at co-localized appointments. Results: Data were available for 49 mothers and 30 infants. All had a history of injection drug use; none reported use during the study. Fifty-two were White and two were Black per self-report; one participant was co-infected with HIV. Due to non-adherence, placement in foster care, and COVID19 related shutdowns, 23 of 30 (77%) of infants were tested, yielding 23 evaluable mother-infant pairs. Of these, 5 infants (22%) completed three study visits, 7 (30%) completed two visits, and 11 (48%) completed one visit. 28 of 54 subjects (52%) were successfully linked to care and completed treatment; all had undetectable HCV RNA at end of treatment. Of the 10 subjects tested 12 weeks after completion of treatment, all had undetectable HCV RNA. One infant had detectable HCV RNA (1/23 - 4%). Conclusion: Co-localization results in increased rates of linkage to care and successful treatment while the observed 4% vertical transmission rate is within previously described rates.

Poster Abstracts

711

Transfer of Sofosbuvir/Velpatasvir Into Breast Milk Catherine A Chappell 1 , Kristina M. Brooks 2 , Jennifer J. Kiser 2 , Brandon Klein 2 , David Nerguizian 2 , Lane Bushman 2 , Hollis J. Laird 3 , Ellen Stewart 3 , Katelyn Kasula 3 , Kyung-min Kwon 4 , Cathleen Letterio 4 , Bruce Kreter 4 , Elizabeth E. Krans 1 1 University of Pittsburgh, Pittsburgh, PA, USA, 2 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 3 Magee–Womens Research Institute, Pittsburgh, PA, USA, 4 Gilead Sciences, Inc, Foster City, CA, USA Background: Treatment of hepatitis C virus in the postpartum period is delayed until after the completion of breastfeeding due to lack of data on infant exposure and safety. Our objectives were to describe breast milk transfer of sofosbuvir (SOF), GS-331007 (SOF inactive metabolite) and velpatasvir (VEL) in postpartum women being treated for HCV with SOF/VEL who were not intending to breastfeed. Methods: Women undergoing postpartum HCV treatment with SOF 400mg/ VEL 100mg daily for 12 weeks and willing to provide pumped breast milk

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