CROI 2019 Abstract eBook

Abstract eBook

Oral Abstracts

Oral Abstracts

88 INCIDENT DIABETES AND GLUCOSE CONTROL AFTER HCV TREATMENT WITH DAAs IN ERCHIVES Adeel A. Butt 1 , Samia Aslam 1 , Peng Yan 1 , Obaid S. Shaikh 1 , Abdul-Badi Abou-Samra 2 1 VA Pittsburgh Healthcare System, Pittsburgh, PA, USA, 2 Weill Cornell Medicine College in Qatar, Doha, Qatar Background: HCV is associated with an increased risk of diabetes. How treatment with newer directly acting antiviral agents (DAA) affects this risk is unknown. Our objective was to determine the effect of DAA treatment upon the risk and incidence of diabetes. Methods: We identified chronic HCV-infected persons treated with pegylated interferon/ribavirin (PEG/RBV) or DAA regimens and propensity-score matched untreated controls. We excluded persons with prevalent diabetes, HIV or HBV coinfection, those treated with both PEG/RBV and DAA regimens. Diabetes was defined using a combination of blood glucose values, prescription of hypoglycemics and ICD-9/10 codes. Results: We identified 4,764 PEG/RBV treated, 21,279 DAA treated, and same number of untreated controls. Diabetes incidence rate [95% CI]/1,000 person- years of follow up were 19.8[18.3,21.4] among PEG/RBV and 9.89[8.7,11.1] among DAA treated persons (P<0.001). Among the treated, rates were 13.3[12.2,14.5] for those with SVR and 19.2[17.4,21.1] for those without SVR (P<0.0001). Treatment was associated with a larger reduction in incident diabetes rate in persons with more advanced fibrosis/cirrhosis (absolute difference 2.9 for FIB-4<1.25; 5.7 for FIB-4 1.26-3.25; 9.8 for FIB-4>3.25). DAA treatment (HR 0.48, 95%CI 0.42,0.56) and SVR (HR 0.81, 95%CI 0.70,0.93) were associated with a significantly reduced risk of diabetes. DAA treated persons had longer diabetes free survival compared to untreated and PEG/RBV treated persons. There was no significant difference in diabetes free survival between untreated and PEG/RBV treated persons. Conclusion: HCV treatment significantly reduces the incidence and risk of subsequent diabetes, driven largely by DAA regimens. Treatment benefit is more pronounced in persons with more advanced liver fibrosis.

87 A PHASE 1 STUDY OF LEDIPASVIR/SOFOSBUVIR IN PREGNANT WOMEN WITH HEPATITIS C VIRUS Catherine A. Chappell 1 , Elizabeth E. Krans 1 , Katherine Bunge 1 , Ingrid Macio 1 , Debra Bogen 1 , Kimberly K. Scarsi 2 , Leslie A. Meyn 1 , Sharon L. Hillier 1 1 Magee–Womens Research Institute, Pittsburgh, PA, USA, 2 University of Nebraska Medical Center, Omaha, NE, USA Background: Hepatitis C virus (HCV) infection is increasing among pregnant women in the United States, increasing the risk of perinatal transmission. Pregnancy is a window of opportunity for health care interventions, including HCV treatment that could improve maternal health and prevent perinatal HCV transmission. There are no published data on the safety or efficacy of HCV direct-acting antivirals in pregnancy. Therefore, the primary objective of this pilot study was to define the safety of and virologic response to ledipasvir 90mg-sofosbuvir 200mg (LDV/SOF) therapy in pregnancy. Methods: In this open-label, phase 1 study, HIV-negative pregnant women with chronic genotype 1 HCV infection were enrolled between 23-24 weeks of gestation and began a 12-week course of LDV/SOF. Participants had to take at least 73 (87%) planned doses to be evaluable. Viral load testing was performed at 7 visits: screening, enrollment, 13-21 days and 5-6 weeks after LDV/SOF initiation, 1-7 days and 12 weeks after LDV/SOF completion, and at delivery. Maternal adverse events, delivery outcomes and the sustained virologic response 12 weeks after therapy (SVR12), defined as undetectable HCV viral load, are reported. Results: Of 28 pregnant women with chronic HCV who screened, 20 were excluded because of genotype 2 or 3 infection (n=10), ongoing illicit drug use (n=4), declining study participation (n=3), intensions to delivery off-site (n=2), and an APRI score of >1 (n=1). Eight women were enrolled, all of whomwere white, with a median age of 32 (range 25-38) years. Seven of the women were HCV infected due to intravenous drug use, 4 of whomwere receiving opioid pharmacotherapy, and one was perinatally infected. Of 7 evaluable patients, the median HCV viral load at enrollment was 518,173 (range 103,457-3,757,923) copies/mL. All had a rapid response to therapy and all achieved SVR12 (Table). All adverse events related to LDV/SOF were ≤ grade 2. All seven participants delivered at termwith undetectable HCV viral loads at delivery. One-year follow-up of infants is ongoing. Conclusion: In this first study of HCV treatment in pregnant women, response to LDV/SOF was similar to the viral response observed in nonpregnant individuals without any safety concerns identified. Larger studies are needed before this strategy can be recommended. A substantial proportion of women screened out due to genotypes 2 or 3 infection, highlighting the importance of further research to expand HCV treatment options in pregnancy.

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CROI 2019