CROI 2018 Abstract eBook

Abstract eBook

Oral Abstracts

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SINGLE CELL VIRAL AND RECEPTOR BAR CODES: BEYOND THE SINGLE CELL TRANSCRIPTOME Eli A. Boritz , NIAID, Bethesda, MD, USA By simultaneously determining millions or billions of individual nucleic acid sequences in a single experiment, next-generation sequencing technologies allow the analysis of rare events even in the context of very large populations. Therefore, these technologies can help facilitate study of HIV genetic variants or HIV-infected cells within highly heterogeneous ex vivo samples from HIV- positive individuals. This talk will consider the application of this experimental approach to key questions in basic and translational HIV research. Specific examples to be discussed include the detection of antiviral drug-resistant virus variants in people not yet treated with drug, and the comprehensive characterization of HIV-infected cellular reservoirs in blood and tissues by single-cell whole transcriptome sequencing. The purpose of this discussion is to update the audience on ongoing work in the field and to prompt consideration of other uses for next-generation sequencing in HIV prevention and therapy studies. SEEING THE FOREST THROUGH THE TREES: USING PHYLOGENETICS TO IMPACT THE EPIDEMIC Susan J. Little , University of California San Diego, San Diego, CA, USA While widespread HIV prevention and treatment approaches have resulted in a reduction in HIV incidence in a small but growing number of countries, HIV incidence continues to increase or remain stable in many populations. These populations or risk networks are often linked by shared structural barriers to care and community-level stigma. Prevention intervention strategies are increasingly turning to more granular approaches to understanding the characteristics of the individuals who continue to transmit and acquire HIV infection in these communities. The identification of risk networks represents an opportunity to better understand the transmission risk parameters that may be shared by groups of HIV infected and at-risk persons. Phylogenetic analyses utilize the increasingly routinely collected HIV genetic sequence data to track and predict HIV transmission dynamics. When paired with traditional epidemiologic determinants of disease, these molecular epidemiologic analyses may be used to better understand the dynamics of regional transmission patterns and to evaluate the impact of prevention interventions. The use of phylogenetics and molecular epidemiology in clinical trials is a new and rapidly growing field of study. This presentation will review phylogenetic outcome measures necessary to evaluate network incidence and clinical trial strategies that utilize these methods to provide more detailed insights into persistent “hotspots” of HIV transmission. These approaches represent a powerful tool in planning more focused prevention interventions to reduce incidence in particular subepidemics. This presentation will also introduce some of the issues surrounding privacy protection related to HIV molecular epidemiological studies. MEASURING THE POPULATION-LEVEL IMPACT OF INTERVENTIONS Jessica E. Justman , ICAP at Columbia University, New York, NY, USA Population-based assessments of treatment and prevention efforts, whether in the setting of research studies or routine service delivery, are an increasingly important tool to evaluate the impact of interventions and inform future action. This talk will provide an overview of methods for measuring the population- level impact of interventions, including serial population cohorts, community- cluster randomized controlled trials, population-based prospective cohorts, modeling, and population-based household surveys. The latter will include a description of the Population-based HIV Impact Assessment (PHIA) Project, which consists of nationally-representative household-based HIV surveys in 14 countries. For each approach, we will review study design, strengths, limitations, optimal settings and an illustrative example of a relevant study. The talk will focus on examples of HIV interventions but these methods are also suitable for assessing the population-level impact of interventions for a wide range of conditions. PRAGMATIC TRIALS Alison Grant , London School of Hygiene & Tropical Medicine, London, UK Pragmatic trials aim to evaluate how an intervention will perform in real-world conditions, contrasting with explanatory trials, which aim to determine whether an intervention can work under experimental conditions. The extent to which a trial is pragmatic can be assessed across multiple domains, including

whether the study population is highly selected or has broader inclusion criteria; the flexibility of delivery of the intervention; whether the follow-up schedule reflects routine practice; and whether the primary outcome is relevant to patients. Pragmatic trials are not less rigorous than explanatory trials, and may be logistically more challenging to implement. The research question should determine whether a more explanatory or a more pragmatic design is needed. Tools which help assess where a trial lies on the spectrum from explanatory to pragmatic may help investigators ensure that their trial design aligns with the research question. INTERACTIVE CASE-BASED WORKSHOP ON HEPATITIS C Moderators: Debika Bhattacharya 1 , Arthur Kim 2 1 University of California Los Angeles, Los Angeles, CA, USA, 2 Harvard Medical School, Boston, MA, USA This interactive case-based session is geared toward clinicians who are involved in HCV treatment. Direct-acting antiviral (DAA) therapies have revolutionized HCV treatment with high sustained virologic response at 12 weeks (SVR12), i.e. HCV cure, in the majority of uncomplicated patients. However, questions remain for several areas of HCV research and clinical care, including the management of HCV in pregnancy, childhood and adolescence, the management of acute HCV infection and DAA failures, and the importance, diagnosis, and management of steatosis before and after HCV treatment. Dr Ravi Jhaveri (University of North Carolina Chapel Hill) will discuss the increase in HCV infections in women of child-bearing age, HCV in pregnancy and HCV mother to child transmission. He will also discuss treatment of HCV in childhood and adolescence. Dr Christoph Boesecke (University of Bonn) will report on the epidemic of acute HCV infection – particularly among HIV-positive men who have sex with men (MSM), the importance of the treatment of acute HCV, reinfection rates in people who inject drugs (PWID) and the distinction between HCV relapse and reinfection. Dr Pablo Ryan (Hospital Universitario Infanta Leonor) will describe clinical cases of HCV DAA failures, the scenarios in which HCV resistance testing should be performed, and review the clinical trials of newly licensed HCV DAAs in the context of re-treatment. Finally, Dr Kathleen Corey (Harvard University) will discuss the diagnosis and management of steatosis, in the context of HCV, both before and after HCV treatment. PREVENTION: STUDIES OF MOTHER-TO-CHILD TRANSMISSION Julie Overbaugh , Fred Hutchinson Cancer Research Center, Seattle, WA, USA An interdisciplinary approach is crucial to addressing the enormous challenges of HIV prevention. Prevention of mother-to-child transmission (MTCT) has made great progress, with contributions across disciplines being central to that success. The Nairobi Breastfeeding Clinical Trial (NBT) was one of the early trials to address risk and correlates of breast milk HIV transmission. The NBT also provided unique opportunities to study viral and immune factors that may contribute to infant infection. Studies from the NBT included defining the role of antibodies in the transmission bottleneck and characterizing the contribution of antibodies to infant outcomes. Study of infants in this cohort also showed the surprising result that they developed neutralizing antibody responses more commonly and rapidly than adults, suggesting infants may provide a roadmap for antibody-based HIV vaccine approaches. In addition, the trial has been leveraged by many labs to understand the structure and antigenicity of a canonical HIV envelope protein, BG505. In this lecture, I will use the NBT and the collaborations that emerged from it to illustrate the potential of interdisciplinary, international collaborations to address important questions relevant to HIV prevention research. Elizabeth A. Bukusi , Kenya Medical Research Institute, Nairobi, Kenya East and Southern Africa account for over 19 of the 37 million people living with HIV, and contribute up to 43% of new infections globally. With a population of just over 40 million, Kenya has approximately 1.5 million individuals living with HIV with 79% on treatment. Kenya is still not on target to achieve the UNAIDS 90:90:90 goals. In this presentation, 'Mich mar Geno' the gift of hope will be presented through the lens of the 3 C's of Capacity, Collaboration and Community, which have shaped the HIV prevention and treatment landscape. Capacity: From a platform of HIV prevention research, building capacity for human resource and infrastructure has contributed to addressing the HIV epidemic both regionally and globally. Training of competent committed

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Oral Abstracts

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10 THE POTENTIAL OF INTERNATIONAL COLLABORATIONS FOR HIV

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11 MICH MAR GENO - THE GIFT OF HOPE

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CROI 2018