CROI 2017 Abstract e-Book

Abstract eBook

Oral Abstracts

96 HEPATITIS B: PROGRESS AND PROSPECTS IN HEPATITIS B VIRUS CURE Patrick Kennedy, Queen Mary Univ London, London, United Kingdom

The treatment paradigm in Hepatitis B Virus (HBV) is on the cusp of major change, with a multitude of novel agents entering various phases of clinical trials. Novel therapies designed to cure HBV should ultimately restore antiviral immunity similar to that seen in those who naturally resolve HBV infection. Achieving HBsAg loss (or functional cure) in Chronic Hepatitis B (CHB) is dependent on a functional efficient HBV-specific adaptive immune response, with potential innate immune interaction; thus global immune restoration is likely to lead to improved treatment outcomes. The current direct antiviral therapies; although able to control viral replication and limit the progression to cirrhosis; require lifelong administration owing to a lack of sustained immune control off therapy, while immune modulation with interferon is only effective in a small proportion of patients. Better utilization of current therapies through combination and/or sequential strategies has recently been investigated by us (and others) and may merit further exploration. Major challenges in the employment of novel therapeutic approaches will be better definition of which cohorts of CHB patients should be targeted and the development of strategies that preferentially suppress HBV replication, reduce or degrade the cccDNA reservoir without generating excess liver damage. HBV therapy may be more effective and even less toxic in subjects with residual HBV-specific T cells without pre-existing liver inflammation. In keeping with this, I will discuss whether young patients with chronic hepatitis B (considered immune tolerant) with normal ALT levels, harbouring more HBV-specific T cells than their adult counterparts (categorised as immune active), may be better candidates for therapy than previously thought. I will discuss strategies to utilise current therapies to harness the immune response, discuss novel agents in the pipeline along with, in whom and how best to utilize these novel therapies in order to achieve functional cure with defined treatment endpoints in CHB. In addition, I will also consider risk- stratifying patients using non-invasive tests, to determine those patients at greatest risk for the development of hepatocellular carcinoma. 97 MANAGEMENT OF CHRONIC HEPATITIS B DURING PREGNANCY Mindie H. Nguyen, Stanford Univ Med Cntr, Palo Alto, CA, USA Chronic infection with hepatitis B virus (HBV) affects more than 240 million individuals globally and can lead to serious complications, such as cirrhosis and hepatocellular carcinoma. While universal maternal screening programs and immunoprophylaxis to newborns have greatly reduced mother-to-child-transmission (MTCT), immunoprophylaxis can fail in up to 30% of infants, especially in mothers with high HBV DNA levels and positive HBeAg. As a result, there has been growing support for the initiation of antiviral therapy during late pregnancy in highly viremic women, and this has been shown in a recent randomized controlled trial to be safe and effective in preventing MTCT with antiviral therapy starting at 30-week gestation and in combination with birth-dose HBV immunoglobulin (HBIG) and vaccination followed by completion of the 3-dose vaccine series. Antiviral therapy may also be initiated to improve maternal outcomes, as immunological changes during pregnancy and post-partum can lead to acute liver failure in women. During pregnancy, cell-mediated immunity is suppressed, possibly due to an increase in adrenal corticosteroids, estrogens, and progesterone, thereby allowing the woman to tolerate the semiallogenic fetus. Post-partum, these changes are reversed. As a result, flares of alanine aminotransferase (ALT) and HBV DNA have been reported during pregnancy as well as the initial post-partum period in HBV-infected women. While most hepatic flares are during late trimester, mild and resolve spontaneously, approximately half can occur during second trimester or earlier and severe cases including liver failure have been reported both during pregnancy and postpartum. The American Association for the Study of Liver Diseases (AASLD) guidelines recommend antiviral therapy for pregnant women with HBV DNA >200,000 IU/mL, even in the absence of clinical symptoms, in order to reduce MTCT, and monitoring for ALT flares every 3 months for 6 months when antiviral therapy is discontinued. However, there is no consensus on the management of HBV in women with HBV DNA ≤200,000 IU/mL, women with active hepatic inflammation or advanced fibrosis, or who become pregnant while on therapy. In general, because significant HBV DNA and ALT flares can occur during pregnancy and early post-partum in women with CHB, HBV-infected women should be closely monitored every 4-6 weeks during pregnancy and early post-partummonths three and six. 98 HEPATITIS C VIRUS: GONE BY 2030? JohnW. Ward, CDC, Atlanta, GA, USA Recognizing hepatitis C virus (HCV) as a major public health threat, the World Health Organization in 2016 released a strategy for global elimination by 2030 (i.e., 90% reduction in HCV transmission and 65% reduction in HCV-related mortality). The United States (US) National Academies of Sciences has deemed US elimination of HCV a feasible goal. HCV-Infected persons born during 1945-1965 are at greatest risk for HCV-related mortality. Certain strategies improve the HCV testing, care, and cure cascade and can reduce HCV- associated deaths. Provider education and adoption of clinical decision tools improve rates of HCV testing. Training and support of primary-care clinicians expand the workforce offering HCV services. Diagnosis of current HCV infection is improved by reflex testing of anti-HCV+ specimens for HCV RNA. Patient navigation services help persons begin and remain in care. At national and health-system levels, implementing policies and setting and measuring performance targets can improve quality of services. Issues with provider reimbursement for HCV treatment limit the number of persons treated through the Affordable Care Act and proposed changes might impact access to care. Creative solutions are needed for universal access to HCV treatment. Reducing US HCV transmission rate by 90% requires a targeted approach. Incidence is rising among persons who inject drugs (PWID); an increasing number of infants are born to HCV-infected mothers. Harm reduction services (e.g., clean injection equipment, drug treatment services) can prevent >70% of infections among PWID; HCV testing and treatment can enhance prevention. Access to these interventions is poor, particularly in areas with high HCV incidence. In the absence of an effective HCV vaccine, reaching elimination goals for transmission will require improved detection and investigation of transmission networks, increased availability of harm reduction services, affordable HCV therapies, and better evidence and capacity to deliver prevention services. Targeted intervention delivery to incarcerated and other vulnerable and marginalized populations is key to achieving elimination goals. With strong societal commitment and support for implementing comprehensive HCV prevention, testing, care, and treatment, HCV can be eliminated as a public health threat in the US. 99 FATTY LIVER DISEASE: A GROWING CONCERN Rohit Loomba, Univ of California San Diego, La Jolla, CA Nonalcoholic fatty liver disease (NAFLD) is the leading cause of the chronic liver disease in the Western World. NAFLD is commonly associated with obesity and metabolic syndrome. It can be broadly sub-classified into two forms: nonalcoholic fatty liver (NAFL), the non-progressive form of NAFLD, and nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD. NASH can lead to progressive fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD associated with metabolic syndrome and obesity is commonly classified as primary NAFLD. NASH is typically associated with presence of steatosis in zone 3, lobular inflammation and ballooning with or without peri-sinusoidal fibrosis among individuals who consume little or no alcohol and do not have any other secondary cause of NAFLD such as hepatitis C infection, medications, lipodystrophy. Human immunodeficiency virus (HIV) infection is also been linked as a cause for secondary NAFLD due to multiple factors including increasing prevalence of metabolic syndrome in patients with HIV, use of antiretroviral therapies, presence of lipodystrophy among others. Recent data suggest that patients with HIV have higher rates of progressive form of NAFLD than non-HIV infected age, sex and Body-mass-index matched controls. There are several emerging non-invasive modalities for assessing presence of NASH and fibrosis that can now be applied to patients with HIV who may be at risk for advanced fibrosis or cirrhosis due to NAFLD. We will discuss novel data on advanced magnetic resonance imaging and elastography and it’s role in disease severity assessment in NAFLD. We will also discuss novel and emerging treatment response assessment in NAFLD and it’s relevance to HIV-associated NAFLD. 100 MTCT: EVOLVING EPIDEMIOLOGY AND PREGNANCY OUTCOMES Roger L. Shapiro, Harvard Schl of Pub Hlth, Boston, MA, USA Dramatic reductions in mother-to-child HIV transmission (MTCT) have accompanied the rollout of Option B+ and test-and-treat strategies throughout the world, with MTCT now below 2% in some high prevalence regions of Africa where it was over 30% early in the epidemic. However, the past decade has also brought with it a better understanding of potential risks associated with 3-drug ART use in pregnancy. Evidence points to associations between ART use (particularly from before conception) and higher risk for adverse

Oral Abstracts

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CROI 2017