CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

12 Integration-Site Analysis Frederic D. Bushman

University of Pennsylvania School of Medicine, Philadelphia, PA, US Background: The lecture will cover analysis of HIV DNA integration sites in model systems, in HIV infected patients, and in human gene therapy.

Methods: With the development of efficient methods for DNA sequence acquistion, it has become possible to study the geomic locations of populations of integrated proviruses. Results: Early studies showed that HIV favors integration target sites within active transcription units quite strongly. This is mediated in part by tethering to the human transcriptional mediator protein LEDGF/p75. Quantification of integration site recovery can be challenging due to distortions in abudance during PCR and other steps—however tracking using the SonicAbundance method overcomes many of these limitations. These methods and a suite of custom bioinformatic tools have been applied to samples of HIV- infected patients and human subjects gene-corrected with lentiviral vectors. Conclusions: Analysis of integration site data can involve a number of challenges—new approaches to analysis and data visualizaiton will be presented. 13 Discovery and Modeling of Genomic Regulatory Networks With Big Data Hamid Bolouri Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, US High throughput sequencing, large-scale data generation projects, and web-based cloud computing are changing how computational biology is performed, who performs it, and what biological insights it can deliver. Here I review the latest developments in available data, methods and software focusing on the modeling and analysis of the gene regulatory interactions in cells. Three key findings are: (A) Although sophisticated computational resources are increasingly available to bench biologists., tailored on-going education is needed to avoid the erroneous use of these resources. (B) Current models of the regulation of gene expression are far too simplistic and need updating. (C) Integrative computational analysis of large-scale datasets is becoming a fundamental component of molecular biology. I discuss current and near term opportunities and challenges related to these three points.

SessionW4Workshop

Room 613

2:30 pm– 4:30 pm Hepatitis C Care in the Interferon-Free Era 14 Acute HCV: Is It Still Important to Diagnose and Treat? Arthur Y. Kim Massachusetts General Hospital, Harvard Medical School, Boston, MA, US

With the advent of 12 week therapies for chronic HCV with high efficacy, the impetus for early identification the acute phase of infection is no longer based on enhanced treatment efficacy. Instead, the rationale for identifying infection is to provide important counseling and care aimed at enhancing personal health and preventing secondary cases. Ongoing trials will determine whether shorter and/or less intensive courses of antivirals during the acute phase of infection will result in excellent cure rates and preserve immune responses that may be important in the prevention of reinfection after viral clearance. 15 Chronic Genotype 1 Infection Debika Bhattacharya University of California Los Angeles CARE Center, Los Angeles, CA, US We will discuss major management issues specific to chronic genotype 1 infection, including methods of disease staging, timing of treatment initation, regimens for treatment, and monitoring during and after treatment. 16 HCV Genotype 3: Our Next Challenge Arthur Y. Kim Massachusetts General Hospital, Harvard Medical School, Boston, MA, US While novel therapies are able to cure the vast majority of individulas with genotype 1, those with genotype 3 have less robust options. Given that it is prevalent throughout the world and is emerging in young injection drug users, advancing therapeutic options for genotype 3 is one of our next challenges. By presenting a case of a prior nonresponder to interferon-based therapies, current and future management options for genotype 3 will be highlighted. 17 HCV Cirrhotics With Early Decompensation Marion G. Peters University of California San Francisco, San Francisco, CA, US HCV cirrhotics decompensate at 5-7% per year with development of varices, ascites, hepatic encephalopathy or synthetic dysfunction. All cirrhotics should be monitored for hepatocellular carcinoma (1-4% develop HCC per year). Ultrasonography is recommended every 6 months (estimated doubling time of HCC 136 days). Quadruple–phase computed tomography or MRI is used to confirm any abnormalities seen. Cirrhotics should undergo upper endoscopy to evaluate for varices. If Grade 2 or greater varices are found, primary prophylaxis with a non-selective beta blocker (propranolol or nadolol) should be initiated to decrease the heart rate by 10%. If beta blockers cannot be tolerated, then band ligation of varices is recommended. Transjugular intrahepatic portosystemic shunting (TIPS) promptly drops portal pressure. All patients with ascites require diagnostic paracentesis to evaluate for portal hypertension and to exclude spontaneous bacterial peritonitis. Portal hypertension is suggested when serum to ascites albumin gradient is ≥ 1.1 mg/dL. Management of ascites includes sodium restriction (<2 g/day) and diuretics: spironolactone combined with furosemide (ratio of 40 mg furosemide: 100 mg spironolactone, increasing as needed). With progression, ascites becomes diuretic refractory and treatment usually requires large-volume paracentesis (LVP) or TIPS. For every liter of ascites removed, 50 cc of 25% salt poor albumin iv must be given. While TIPS is associated with greater transplant-free survival than LVP, it also has a much higher rate of hepatic encephalopathy. The new all oral direct acting antiviral agents (DAA) for HCV have permanently changed the treatment landscape for patients with end stage HCV. The current AASLD/IDSA 2014 guidelines (http://www.hcvguidelines.org) recommend that patients with decompensated cirrhosis should have an experienced HCV treater and be referred for liver transplant evaluation. Recommended regimens for genotype 1 and 4 are daily fixed-dose combination ledipasvir (90 mg)/sofosbuvir (400 mg) with RBV for 12 weeks in naïve patients, and 24 weeks in prior sofosbuvir failures. If RBV intolerant, daily fixed-dose combination ledipasvir (90 mg)/sofosbuvir (400 mg) for 24 weeks is recommended. The regimen for Genotype

Oral Abstracts

87

CROI 2015