CROI 2019 Abstract eBook

Abstract eBook

Oral Abstracts

have been linked to alterations to the microbiome. There are currently >1000 registered clinical trials examining microbiome-based interventions to promote human health and its role in disease, underscoring this expanding field of research. In HIV, the microbiome has been associated with HIV transmission and infection, mucosal inflammation, immune responses to vaccines, and efficacy of topical antiretroviral-based microbicides. Therefore, integrating microbiome sub-studies in future clinical trials will be an important component for HIV prevention and treatment strategies. In this seminar I will provide an overview of the basics of the microbiome, methods to measure its different components, how to interpret data, examples of how this can be integrated it into clinical studies and provide highlights on the microbiome in HIV and human disease. MISSING U: HANDLING AND AVOIDING MISSING DATA IN CLINICAL TRIALS Heather Ribaudo , Harvard T.H. Chan School of Public Health, Boston, MA, USA Randomized clinical trials are the gold standard for evaluation of interventions. However, the presence of missing data can compromise their benefits, and lead to bias and inappropriate study conclusions. While methods exist to handle missing data in analysis, these may appear intimidating to the statistician and non-statistician alike, and are generally under-utilized. Even when used, handling of missing data in analysis can only do so much, and it has long been advocated that considerations for minimizing missing data must start at trial design. At the request of the FDA, the National Research Council (NRC) recently convened a panel of experts to consider current state-of-the-art for handling missing data in clinical trials. The panel recommendations reinforced previous considerations and introduced some new ideas and concepts to be considered in the design and analysis of clinical trials to mitigate the impact of missing data. This talk will demonstrate the issues associated with inappropriate handling of missing data and attempt to demystify the associated analysis methodology. The recommendations of the NRC panel will be presented, including an introduction to the definition of estimands in study design and a discussion of appropriate sensitivity analyses. Examples from HIV clinical trials for both treatment and prevention will be used throughout to help demonstrate and solidify concepts. By the end of the talk, the audience will be familiar with terminology associated with missing data and have an understanding of the appropriate points to consider, and tools to implement, in clinical trial planning, analysis, and reporting to minimize the impact of missing data. DESIGNING AND INTERPRETING HIV PREVENTION TRIALS IN THE ERA OF EFFECTIVE INTERVENTIONS David Dunn , University College London, London, UK Until recently, the design and analysis of clinical trials to evaluate HIV prevention interventions was relatively straightforward. Participants would be randomised to receive the intervention of interest or to receive no intervention (placebo under the most robust design). The analysis would compare HIV incidence rates between the groups, yielding an estimate of the effectiveness – the proportionate reduction in incidence – achieved by the intervention. This model of experimental simplicity was ended with the discovery of the remarkable effectiveness of oral pre-exposure prophylaxis (PrEP) using TDF-FTC. This meant it became ethically unacceptable to include a no intervention group in most study populations. Current studies of novel PrEP agents have instead been designed as non-inferiority trials in which the experimental arm is compared with an active-control TDF-FTC arm. The challenges in analysing and interpreting such trials will be discussed, pointing out the need to collect additional contextual information. A different perspective is required for the evaluation of other prevention interventions, including vaccines. Here, the primary interest may be in estimating biological efficacy rather than a direct comparison with oral PrEP. Nevertheless, the ethical requirement to offer PrEP complicates trial design and interpretation, as well as potentially requiring much larger studies. This session will attempt to illuminate key, basic concepts, keeping statistical detail to a bare minimum. INTERACTIVE CASE-BASED WORKSHOP ON LIVER DISEASE Marion G. Peters 1 , Andri Rauch 2 1 University of California San Francisco, San Francisco, CA, USA, 2 University Hospital Bern, Bern Switzerland This interactive case-based session is geared toward clinicians who are involved in treatment of HIV-infected patients with various liver diseases. Despite major recent breakthroughs in the treatment of viral hepatitis,

there are important remaining challenges in the clinical care of those with liver diseases. This workshop will address difficult to treat HCV-coinfected patients who have failed direct-acting antiviral (DAA) therapies, highlight the important but often ignored hepatitis D and E viruses, and address the epidemiology and management of nonalcoholic fatty liver disease (NAFLD). Dr Sven Pischke (University Hospital Hamburg-Eppendorf) will discuss issues in diagnosis, clinical features, and treatment of Hepatitis E. He will highlight geographic differences in epidemiology and testing, and address the current management strategies. Dr Jeffrey Glenn (Stanford University) will provide an overview of current diagnostic tests, clinical challenges and emerging new therapies for Hepatitis D, and the varied prevalence throughout the world. Dr Giada Sebastiani (McGill University) will discuss NAFLD and its complex multifactorial pathogeneses, including frequent metabolic comorbidities and lifelong use of antiretroviral therapy and HIV itself, which is thought to drive this epidemic. She will highlight that early diagnosis, preventive and therapeutic strategies may help reduce the burden of NASH in people living with HIV. Dr John Scott (University of Washington) will describe HCV DAA failures, the scenarios in which HCV resistance testing should be performed, and the choices of therapy for patients with end-stage liver disease. This presentation will describe the newly announced U.S. Department of Health and Human Services initiative targeting the ongoing HIV epidemic in the United States with the goals of decreasing the number of HIV incident infections by 75%within 5 years, and then by 90%within 10 years. This coordinated, multi-agency initiative will focus on geographic and demographic hotspots in 48 counties, Washington D.C., and Puerto Rico where the majority of new HIV cases are reported, as well as in 7 states with a disproportionate occurrence of HIV cases in rural areas. This new initiative builds on the scientific findings over the past 4 decades in HIV prevention, treatment, and care. Under the leadership of the Assistant Secretary for Health, HHS agencies including NIH, CDC, HRSA, and IHS will coordinate their programs and resources to implement with local, regional, and state partners evidence-based strategies to diagnose, treat, prevent, and rapidly detect and respond to the continuing HIV spread in the U.S. This HHS initiative will focus on interrupting or disrupting the kinetics of HIV spread and provide a way forward to ending the epidemic in this country. Combination antiretroviral therapy (ART) has revolutionized the treatment and prevention of HIV-1 infection. Taken daily, ART prevents and suppresses the infection. However, ART interruption almost invariably leads to rebound viremia in infected individuals due to a long-lived latent reservoir of integrated proviruses. Therefore, ART must be administered on a life-long basis. The lecture will focus on emerging preclinical and clinical studies that suggest that immunotherapy may be an alternative or an adjuvant to ART because in addition to preventing new infections, anti-HIV-1 antibodies clear the virus, directly kill infected cells and produce immune complexes that can enhance host immunity to the virus. 11 THAILAND’S ACHIEVEMENTS IN HIV TREATMENT, PREVENTION, AND CURE RESEARCH Praphan Phanuphak , Thai Red Cross AIDS Research Center, Bangkok, Thailand To the external world, Thailand has achieved considerably on HIV treatment, prevention, and cure research but the reality could be different. For HIV treatment, even with Universal ART Coverage since 2006 and the Treat-All policy since 2014, the "second 90" is still far below with a median CD4 count at ART initiation of <150 cells/ML in Thailand. To close this gap, “Same-Day ART (SDART) Initiation Hub” was launched at the Thai Red Cross Anonymous Clinic (TRC-AC). In one year, 77% of 2,000 PLHIV started ART on the day of diagnosis and another 19% in a week. However, the Thai government and most ID doctors are still too afraid of SDART since even in the US it has not yet been implemented and WHO puts SDART only as a subset of Rapid ART. Only 54% of PLHIV in Thailand reached undetectable viral load. This, coupled with low ‘consistent condom use’ rate among key populations, dictates the urgent need of PrEP. Providers who serve MSM, transgender women, and sex workers have been (2010) SPECIAL PRESENTATION ENDING THE HIV EPIDEMIC: A PLAN FOR THE UNITED STATES Anthony S. Fauci, MD , NIAID, Bethesda, MD, USA 10 DISCOVERY AND DEVELOPMENT OF HIV BROADLY NEUTRALIZING ANTIBODIES Michel Nussenzweig , The Rockefeller University, New York, NY, USA

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CROI 2019