CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

707 Prevalence of HDV in a Midwestern HIV-HBV Coinfected Population Sanam Razeghi ; Susan Rouster; Kenneth E. Sherman University of Cincinnati, Cincinnati, OH, US

Background: Hepatitis D virus (HDV), a defective RNA virus leads to the most aggressive form of viral hepatitis. HDV is thought to be relatively uncommon in the U.S. and its prevalence and significance in those with HIV is virtually unknown. Furthermore, serologic detection methods may under-represent true prevalence. We sought to assess the prevalence of HDV RNA in a Midwestern cohort of patients with HBV-HIV coinfection and a comparison group with HBV alone. Methods: We developed and validated a qRT-PCR methodology for detection of HDV RNA. Briefly, viral RNA was extracted using a QIAamp viral RNA mini kit, followed by qRT-PCR in a BioRad CFX96 platform. A 93 BP region was amplified. The assay was validated by sequence analysis of the amplicon products with comparison to published sequences. The initial cohort was then tested and associated clinical data were obtained. Statistical analysis was performed using Statistix 10.0. Results: 138 subjects (48 HBV-positive/HIV-negative and 90 HBV-positive/HIV-positive) were evaluated. The mean age was 38. 83%were male. 17%were on HBV active therapy. Two subjects were found to be HDV RNA positive, both from the HBV/HIV group. The mean ALT level in the HDV positives was 228 U/L vs. 96 U/L in HDV negative. Both were African- American; one was born in the U.S. and the other in Africa. Cirrhosis was not present in either patient. Neither reported IDU as a risk factor. No samples were positive in the cohort with HBV alone. Conclusions: Our analysis suggests HDV prevalence in those with HBV/HIV coinfection of 2% (p = 0.2, CI 0-5.3%) as compared to 0% in the HIV-negative cohort. Cirrhosis was not present in either subject found to have HDV coinfection though mean ALT level was higher. Further analysis of larger cohorts appears warranted because presence of HDV RNA was unsuspected in these patients. 708LB Oral Prenylation InhibitionWith Lonafarnib in Chronic Hepatitis D Infection: A Randomized, Double-Blinded, Placebo-Controlled Proof-of-Concept Study Christopher Koh 1 ; Laetitia Canini 7 ; Harel Dahari 2 ; David Cory 3 ; Ingrid Choong 3 ; David Kleiner 4 ; Stewart Cooper 6 ; Mark A.Winters 5 ; Jeffrey Glenn 5 ;Theo Heller 1 1 National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Fulton, MD, US; 2 Loyola University Medical Center, Maywood, IL, US; 3 Eiger BioPharmaceuticals, San Carlos, CA, US; 4 National Cancer Institute, Bethesda, MD, US; 5 Stanford University, Stanford, CA, US; 6 California Pacific Medical Center, Palo Alto, CA, US; 7 University of Edinburgh, Edinburgh, United Kingdom Background: Interferon therapy for chronic delta hepatitis (HDV) infection is unsatisfactory. In in vivo models, prenylation inhibition has proven effectiveness against HDV. In a first-in-human for HDV, proof-of-concept study, we evaluated the antiviral effects and safety of the prenylation inhibitor, lonafarnib (LNF), in patients with chronic HDV. Methods: HDV patients were sequentially enrolled into 2 groups in a phase 2a double-blinded, randomized, placebo-controlled study and received: LNF 100 mg (Group 1) or LNF 200 mg (Group 2) twice daily for 28 days followed by 6 months of follow-up. Both groups enrolled 6 treatment and 2 placebo subjects, where Group 1 placebo subjects were offered open-label LNF in Group 2. Patients had 72-hour viral kinetic and pharmacokinetic evaluations at the start of therapy. Serial measurements of safety parameters, liver tests, pharmacokinetics, and virologic (HDV RNA and HBV DNA) markers were obtained. Mathematical modeling of HDV clearance and LNF effectiveness was performed. Results: In this completed study, the 14 patients were mostly male (71%) with a median age of 38 years and included Asian (50%), Caucasian (43%) and African (7%) subjects. Median baseline evaluations include: ALT (89 IU/mL), AST (61 IU/mL), Ishak fibrosis (3), HBV DNA (<21 IU/mL) and HDV RNA (1.01x10 6 IU/mL). There were no differences in baseline parameters between groups. After 28 days of therapy, compared to placebo, the mean log HDV RNA decline from baseline was 0.73 log IU/mL in Group 1 (p=0.04) and 1.54 log IU/ mL in Group 2 (p=0.002). LNF serum concentrations correlated with HDV RNA change (r 2 =0.78, p<0.0001). HDV RNA decay was biphasic in most patients. The 1 st phase lasted 9.0 (IQR=7.6;14.0) vs. 5.0 (IQR=4.1;6.0) days (Group 2 vs. Group 1) with greater decline in Group 2 vs. Group 1 (1.35 [IQR=1.34;1.51] vs. 0.61 [IQR=0.42;0.83] log IU/ml). The overall 2 nd phase decline slope was -0.12 (IQR=-0.18;-0.01) log IU/wk. There were no treatment discontinuations due to adverse events and no evidence of virologic resistance. Adverse events included mild to moderate nausea, vomiting, dyspepsia, anorexia, diarrhea, and weight loss.

Poster Abstracts

HDV RNA Decline After 28 Days of Lonafarnib Therapy Conclusions: This is the first demonstration in patients that treatment of chronic HDV with the prenylation inhibitor LNF significantly reduces virus levels. The decline in virus levels significantly correlated with serum drug levels, providing further evidence for the efficacy of prenylation inhibition in chronic HDV. 709 Incidence of Hepatitis E Virus in HIV-Infected Patients: A Longitudinal Prospective Study Antonio Rivero-Juarez 1 ; Loreto Martinez-Dueñas 1 ; Antonio Martinez-Peinado 2 ; Angela Camacho 1 ; Celia Cifuentes 3 ; Ana Gordon 1 ; Mario Frias 1 ; JulianTorre-Cisneros 1 ; Juan A. Pineda 3 ; Antonio Rivero 1 1 Instituto Maimonides de Investigación Biomédica de Córdoba, Cordoba, Spain; 2 Instituto Maimonides de Investigación Biomedica de Córdoba, Cordoba, Spain; 3 Hospital Universitario de Valme, Seville, Spain Background: Hepatitis E virus (HEV) incidence in HIV infected patients has not been well established. Studies reporting HEV seroprevalence and incidence in this populations present several methodological limitations such as retrospective analysis and small population samples. As a result, the current magnitude of this emerging disease in this population cannot be established. Therefore, we designed a study to evaluate the incidence of HEV and its clinical implications in HIV infected patients. Methods: Prospective study in Southern Spain that included HIV-infected patients who were followed up between September 2012 and July 2014. All patients included were tested for anti-HEV IgG using EIA (Wantai HEV-IgG ELISA). All anti-HEV negative patients were prospectively followed-up during 1 year. In these patients an EIA anti-HEV IgG was performed each 6. In those patients with anti-HEV IgG positive, a RT-PCR was performed (amplicube HEV). Clinical and demographic variables were collected at baseline and during the follow-up. Incidence rate was calculated.

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CROI 2015