CROI 2020 Abstract eBook

Abstract eBook

Oral Abstracts

transmitted infections), social and structural barriers to research, prevention, treatment, access, care, and support. Traditional models of infectious disease clinical research needed to be adapted to the complex disease settings and diverse populations which made studying HIV and its complications more challenging than studies of a single drug for a single infectious agent. In this talk I will review 1) contributions made by activists, people living with HIV, and their communities to restructure and reform clinical trial designs to make themmore relevant, ethical and efficient in the early days of clinical HIV research, including by expanding eligible trial populations and changing trial designs to make them more flexible, inclusive, and adapted to the real needs of people living with HIV; 2) the impact of broadened inclusion criteria and community priorities on HIV clinical research in the discovery of highly effective combination therapy (cART), pre-exposure prophylaxis (PrEP), and defining the optimal time to begin cART in all people living with HIV; and 3) current challenges and opportunities facing trial designers and networks in selected key high priority populations including those co-infected with HIV and Mycobacterium tuberculosis and those at risk for those infections in current and upcoming multi-modality prevention and treatment trials in selected diverse populations. I will close with some observations about the impact of diverse community engagement and participation in all aspects of the clinical trial process. WHEN AT THIRD YOU DON'T SUCCEED David L. Wyles , Denver Health and Hospital Authority, Denver, CO, USA Current HCV direct acting antiviral (DAA) regimens are highly efficacious; including in populations previously recognized to have poor responses to interferon-based therapies (e.g. HIV co-infection, cirrhosis etc.). However, as DAAs are used in a greater number of patients in clinical practice, scenarios which have not been adequately addressed in clinical trials, or are impractical to study, will invariably arise. The approach to management of HCV treatment interruptions of varying durations at different times during therapy and re- treatment for multiple DAA regimens failures are examples of such scenarios. In this interactive session, cases will be used to highlight clinical conundrums focusing on: • Determination or HCV relapse versus reinfection • Multiple DAA regimens failure retreatment • Approach to treatment interruptions during DAA therapy While FDA approved options for retreatment exist for initial DAA regimen failure, robust data are lacking for patients failing multiple DAA regimens and retreatment approaches are not standardized. Inferences from studies in other HCV scenarios can provide insight into reasonable re-treatment approaches which generally rely on extension of therapy with addition of other drug classes and ribavirin when possible. In situations where no data exists- such as evidence based approaches for dealing with treatment interruptions, expert opinion and audience input will be used to offer management options. “A” CASE TO REMEMBER: HEPATITIS A - MANAGING AN OLD VIRUS IN NEW POPULATIONS AT RISK Darcy Wooten , University of California San Diego, San Diego, CA, USA This session will use a case-based approach with audience response questions to review important updates in epidemiological risk factors for hepatitis A virus (HAV) infection, unusual presentations and complications that occur with HAV, and strategies for prevention. Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death globally. Viral hepatitis, specifically hepatitis B and hepatitis C infections are a major cause of HCC. Antiviral therapies for both HBV and HCV infection can decrease the risk of HCC. This presentation will focus on the contribution of HCC to global liver-related mortality and the impact of antiviral therapies on the incidence of HCC. This presentation will discuss the emerging data on the impact of direct-acting antivirals (DAA) on HCC incidence and recurrence and on the role of DAA therapies in patients diagnosed with HCC. In particular, the presentation will discuss in detail (1) the evidence supporting the safety of DAA therapies in patients with cirrhosis as it relates to risk of HCC development, (2) the optimal timing for initiating DAA therapy in patients who have been diagnosed with HCC and will discuss the impact, if any, of HCC diagnosis on response to DAA therapy, and (3) the impact of SVR on HCC incidence. Lastly, the presentation will discuss monitoring for HCC after SVR in patients with HCC and will highlight emerging Hepatocellular Carcinoma Susanna Naggie , Duke University, Durham, NC, USA

non-invasive biomarkers that may be utilized after DAA HCV cure to improve risk stratification. When possible the presentation will discuss differences in HCC presentation and outcome in people with HIV and viral hepatitis. NONALCOHOLIC STEATOHEPATITIS Kathleen E. Corey , Massachusetts General Hospital, Boston, MA, USA Non-alcoholic fatty liver disease (NAFLD) impacts affecting 25% of adults worldwide. NAFLD is a spectrum of pathology including steatosis and non-alcoholic steatohepatitis (NASH), the progressive form of NASH which can lead to fibrosis development, cirrhosis, end-stage liver disease, and hepatocellular carcinoma. NASH cirrhosis is the second leading indication for liver transplantation in the United States. In addition, NAFLD is strongly associated with the metabolic syndrome and obesity and is an independent risk factor for cardiovascular disease (CVD) and CVD-related death. In persons with HIV (PWH) liver disease is a significant cause of mortality. With the high prevalence of diabetes and metabolic disease in PLWH, NAFLD and NASH are being increasingly diagnosed. This talk will present strategies for the risk factors for and diagnosis and management of NAFLD in PWH. THE ANCIENT AND MODERN ORIGINS OF HIV Michael Emerman, Fred Hutchinson Cancer Research Center, Seattle, WA, USA How did HIV-1 become a human pathogen? In this talk, I will trace the origins of HIV-1 through the cross-species transmissions and viral adaptations that preceded its emergence in humans. The immediate precursor of HIV-1 is a virus that infects chimpanzees, Simian Immunodeficiency Virus of Chimpanzees (SIVcpz). SIVcpz is itself derived from other SIV lineages that infect old world monkeys. Cross-species transmission events require mutations to the viral genome that allow adaption to replicate in a new host. Much of this adaptation involves gaining the ability to counteract or evade a repertoire of antiviral genes, called restriction factors. The selective pressure between host restriction factors and the viral proteins that antagonize these factors sets up an “arms- race” that can be read out in the rapid evolution of the two proteins. The example of such restriction factors and viral antagonists that I will describe in the most detail is that of the primate APOBEC3 proteins that hypermutate viral genomes and the lentiviral Vif proteins that antagonize APOBEC3 activity. Study of the functional and evolutionary relationships between APOBEC3 proteins in primates and Vif proteins in primate lentiviruses allow us to make inferences about how long lentiviruses have been present in primates and about the steps that occurred for a lentivirus in monkeys to adapt to replicate first in chimpanzees, and then in humans. This talk will also highlight the role that basic science can play in ending the current HIV-1 pandemic. 16 TRANSLATING HIV SCIENCE INTO POPULATION IMPACT: A REALITY CHECK FROM THE FRONTLINE Alex G. Coutinho , Partners in Health, Kigali, Rwanda Over the past 20 years, tremendous strides have been achieved in the response to HIV/AIDS, especially in the incredible scale-up of life-saving ART to over 25 million people globally, most of them in Africa. This heroic achievement has resulted in an estimated 56% reduction in mortality since 2004 and as a consequence led to an increasing life expectancy and a marked drop in HIV/ AIDS orphans – all of which are significant population impacts. However, the expected reductions in new infections have only been achieved modestly with an estimated reduction of HIV incidence of 16% in the 10 years since 2010. This is in part due to the challenge of translating scientifically proven HIV prevention interventions like ART, PMTCT, and VMMC and PreP into an environment that has many obstacles and challenges that include funding constraints, struggling health systems, disempowered communities and structural barriers. In particular, HIV prevention faces the challenge of promoting approaches like condoms that often face opposition from some politicians, cultural leaders, and religious leaders. Other approaches like VMMC and PreP face both opposition and skepticism, on the grounds that there are fears that individuals using these partially effective approaches will exhibit a rebound increase in risky sexual behaviors that will lead to new HIV infections. In addition, many of the target populations that are at greatest risk for HIV infection are also the groups that are the hardest to reach because they are considered illegal, are harassed and discriminated and often live and operate underground to avoid scrutiny. However, there are several excellent examples of effective scale-up of scientifically proven interventions and population impact, as well as a few examples of large scale combination HIV treatment/prevention interventions 14 15

Oral Abstracts

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CROI 2020