CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

552

Assessment of Hepatic Antifibrotic Effect of Cenicriviroc in Patients With HIV Enass Abdel-Hameed ; Susan D. Rouster; Kenneth E. Sherman Univ of Cincinnati, Cincinnati, OH, USA

Background: Chronic liver disease is frequently observed in HIV-infected patients and is multifactorial. Attenuation of fibrotic progression may improve liver-related morbidity and mortality. Cenicriviroc (CVC) is an oral, dual antagonist of CCR2/CCR5, which are involved in key pro-inflammatory and fibrogenic pathways. We evaluated effects of 2 doses of CVC on serum hepatic fibrosis biomarkers in HIV+ subjects treated in a Phase 2b study (NCT01338883). Methods: Patients with CCR5-tropic HIV-1 were randomized to receive CVC 100 mg (n=59), CVC 200 mg (n=56) or Efavirenz (EFV) (n=28), each combined with emtricitabine/ tenofovir for 48 weeks. The Enhanced Liver Fibrosis (ELF) biomarker index was evaluated in a subset of patients who completed 48 weeks of treatment and had paired baseline and 48-week samples. The ELF index has been validated previously in patients with NASH, HCV and HBV infection, and by our lab in HIV patients with liver disease. The ELF index was calculated from the results of 3 serum biomarkers of collagen and extracellular matrix deposition: hyaluronic acid, propeptide of type III procollagen, and tissue inhibitor of metalloproteinase-1. Results: Paired baseline and 48-week samples were randomly selected for 72/100 subjects completing the study: CVC 100 mg arm (n= 20/42), CVC 200 mg arm (n= 36/41) and EFV controls (n= 16/17). No subjects were coinfected with HCV or HBV. Among subjects receiving CVC 100 mg and 200 mg, the ELF scores at baseline were 9.80 ± 0.96 and 10.53 ± 2.12 and after 48 weeks were 9.93 ± 1.00 and 8.28±0.09, respectively. Subjects who received EFV had a mean ELF score of 9.13±0.98 at baseline and 9.28 ± 1.06 after 48 weeks. ELF scores decreased significantly in patients who received CVC 200 mg after 48 weeks of treatment ( p <0.0001) but remained unchanged in patients who received EFV or CVC 100 mg. HIV suppression was similar in all groups. Conclusions: Daily administration of CVC 200 mg for 48 weeks was associated with a significant decrease in specific biomarkers of hepatic fibrosis encompassed by the ELF index. This was not observed in control subjects treated with EFV nor with the lower dose of CVC (100 mg) (with caveat that < 50% of paired samples tested to date). Clinical trials of CVC are underway in adults with NASH and liver fibrosis, using a new single tablet formulation of CVC 150 mg providing drug levels comparable to CVC 200 mg in the HIV Phase 2 trial. Evaluation of CVC in HIV patients who are at risk of liver fibrosis progression is warranted. 553 Background: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent among people living with HIV. Among non-HIV patients, limited studies suggest potential benefit of statins in patients with NAFLD. Non-contrast computed tomography (CT) allows for the measurement of liver density (attenuation). Liver density is inversely correlated to fat content and has been validated as an accurate, reproducible means to characterize hepatic steatosis. Thus, we leveraged data obtained using CT in a trial of statin therapy, focusing on a subgroup with NAFLD to determine the effect of a statin on liver fat. We hypothesized that statins would reduce hepatosteatosis. Methods: We had previously performed a randomized, double-blind, placebo-controlled trial in HIV patients on stable anti-retroviral therapy with subclinical coronary atherosclerosis and LDL-cholesterol < 130mg/dL. Forty HIV-infected subjects were enrolled and assigned to placebo (n=21) or atorvastatin (n=19) for 12 months. Patients with AST or ALT 3x > upper limit of normal and active liver disease were excluded. Subjects underwent CT imaging with measurements of liver and spleen attenuation, and metabolic assessments including fasting lipids, anthropometric measurements and cross-sectional abdominal CT to assess VAT at baseline and end of the study. Results: NAFLD was identified in 9 participants at baseline using a liver-to-spleen attenuation ratio cutoff < 1, in whom these analyses were performed. Among these subjects, liver-to-spleen attenuation ratio increased in the atorvastatin group, 0.46 ± 0.27 compared to a mean decrease of -0.04 ± 0.14 in the placebo group (p = 0.02)( Figure Panel A ), indicating a reduction in hepatosteatosis with atorvastatin. Atorvastatin reduced liver fat without a change in BMI or VAT. The change in liver-to-spleen attenuation ratio was significantly associated with change in LDL (r= -0.83, p= 0.02)( Figure Panel B ), but not other lipid, metabolic or inflammatory parameters. Conclusions: To our knowledge, this is the first report suggesting an effect of statin therapy to reduce liver fat in the HIV population. The change in liver fat significantly correlated with reduction in LDL by statin therapy. These data provide rationale for future larger trials in HIV patients with NAFLD to assess the potential beneficial effects of statins in reducing liver fat. Statin Therapy Reduces Liver Fat Measured by Computed Tomography in Patients With HIV Janet Lo ; Michael Lu; Elli Kim; Eric Nou;Travis R. Hallett; Jakob Park; Udo Hoffmann; Steven Grinspoon Massachusetts General Hosp, Boston, MA, USA

Poster Abstracts

554 PEth Improves Detection of Alcohol and Associated Mortality Among HIV+/HCV+

Amy C. Justice 1 ; Kathleen A. McGinnis 2 ; JanetTate 3 ; David A. Fiellin 4 ;Vincent Lo Re 5 ; Joseph Jones 6 ; Judith A. Hahn 7 ; Kendall J. Bryant 8 ; for theVACS ProjectTeam 1 Yale Univ, New Haven, CT, USA; 2 VA Pittsburgh Hlthcare System, Pittsburgh, PA, USA; 3 VA Med Cntr, West Haven, CT, USA; 4 VA Connecticut Hlthcare System, New Haven, CT, USA; 5 Univ of Pennsylvania, Philadelphia, PA, USA; 6 US Drug Testing Lab, Des Plaines, IL, USA; 7 Univ of California San Francisco, San Francisco, CA, USA; 8 Natl Inst on Alcohol Abuse and Alcoholism, Bethesda, MD, USA Background: Abstinence from alcohol is recommended for individuals co-infected with HIV and hepatitis C (HIV+/HCV+) making self-report subject to social desirability bias. Phosphatidylethanol (PEth), an abnormal phospholipid formed only in the presence of ethanol, can detect exposure for up to 14 days. Any detectable amount suggests exposure, but the most commonly used cut off is 8-19 ng/mL. Higher cutoffs, 20-80 ng/mL, have been proposed for harmful use. Using data from the Veterans Aging Cohort Study, we evaluate agreement between PEth and self-report (AUDIT-C) among HIV+/HCV+ and whether PEth demonstrates a stronger association with mortality.

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CROI 2016