CROI 2019 Abstract eBook

Abstract eBook

Oral Abstracts

ORAL ABSTRACTS

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PROGRAM COMMITTEE WORKSHOP FOR NEW INVESTIGATORS AND TRAINEES John W. Mellors 1 , Serena S. Spudich 2 1 University of Pittsburgh, Pittsburgh, PA, USA, 2 Yale University, New Haven, CT, USA Each year, the Program Committee for the Conference for Retroviruses and Opportunistic Infections (CROI) presents a half-day workshop geared toward new investigators and trainees. The goal of the workshop is to provide a broad introduction to key topics in basic, clinical and public health research, summarizing recent advances, areas of controversy and important knowledge gaps, along with a road map to relevant abstracts and presentations at CROI 2019. Presentations at the workshop are given by members of the CROI Program Committee. This year, the programwill begin with a talk by Dr Paul Bieniasz who will review aspects of the HIV-1 replication cycle, in particular recent developments in the understanding of virus entry, capsid function and RNA turnover. Following this, Dr Penny Moore will describe advances in eliciting protective HIV-1 antibodies by vaccination, highlight emerging insights at the interface between innate and adaptive immunity, and summarize new immunological findings relevant to HIV-1 to be presented at the conference. Dr Sharon Hillier will then describe the current landscape of biomedical HIV-1 prevention research including vaccines, broadly neutralizing antibodies, oral and injectable pre-exposure prophylaxis, vaginal and rectal microbicides, and combination approaches for prevention of HIV-1. Dr Constance Benson will next briefly summarize the current state-of-the-art for tuberculosis treatment and prevention, highlight recent developments in the field, including new data to be presented at CROI, and identify current knowledge gaps that need to be addressed. Finally, Dr Katharine Bar will review the current understanding of HIV-1 persistence, highlight major obstacles to achieving a cure for HIV-1, and discuss pre-clinical and clinical developments in HIV-1 cure research. Workshop participants are encouraged to interact with speakers during the moderated discussion after each talk. By the completion of the workshop, attendees will have achieved a head start toward maximizing the knowledge gained and research ideas arising from CROI 2019. DISCOVERING THE ART IN SCIENCE (AND MEDICINE): THE HUMAN CONNECTION Dawn Averitt , The Well Project, Women’s Research Initiative on HIV/AIDS, South Strafford, VT, USA The scientific frontier is vast and our ongoing exploration continues to unveil stunning revelations impacting technology, medicine, and human health. However, the complexity of a person (not just a patient) introduces both an opportunity and a challenge to translate our knowledge of science into the art of medicine. Recognizing, if not understanding, the nuanced biologic, physiologic, emotional, and societal influences impacting people of different ages, races, sex, or gender provides boundless opportunities in research and medicine to uncover possibility and challenge long held assumptions. ENGINEERING THE LATENT RESERVOIR Paula Cannon ,University of Southern California, Los Angeles, CA, USA HIV persists in infected individuals despite antiretroviral therapy (ART). This is because the virus inserts itself into the genomes of infected cells where it can, under certain conditions, become transcriptionally silent or latent. These latent viruses are not impacted by ART but retain the potential to be reactivated at a later timepoint. In this way, latent HIV shares many of the features of a genetic locus, including sensitivity to the cell’s transcriptional or activation state. The recent development of sequence-specific genome editing tools such as CRISPR/Cas9, is suggesting new ways to consider depleting or mitigating the effects of the latent reservoir. Current genetic approaches against HIV infection include: (1) strategies to create HIV resistant cells, for example by disabling the non-essential CCR5 co-receptor gene in CD4 T cells or their precursor hematopoietic stem cells; (2) strategies to boost or artificially redirect immune responses to recognize infected cells; and (3) strategies to target integrated HIV

genomes themselves for disruption, suppression or activation. The first two approaches have the advantage of being amenable to ex vivo cell engineering, the capabilities for which have greatly advanced in recent years. Strategies targeting the HIV genome itself, however, will require the development of in vivo delivery methods that can find the needle in the haystack that an integrated latent HIV genome represents. 4 NOVEL IMAGING APPROACHES TO CHARACTERIZE AND QUANTIFY VIRAL RESERVOIRS Jake D. Estes , Oregon Health and Sciences University, Portland, OR, USA Effective combination antiretroviral therapy (cART) for HIV has led to vastly improved survival when treatment is available and affordable, an outcome that relies on uninterrupted adherence to cART for life. In the quest for sustained viral remission in the absence of cART (i.e. functional cure) or the complete eradication of HIV from infected individuals, it is necessary to understand the sizes, locations and characteristics of the reservoirs throughout the body fromwhich infection can rebound after treatment is suspended. In addition, understanding HIV reservoirs in the context of their resident immune “neighborhoods” and surrounding inflammatory “landscapes” will likely be important to determine key mechanisms of viral persistence and potentially identify opportunities or pathways to exploit for future viral remission and eradiation strategies. In this talk, I will discuss advances in approaches to image viral reservoirs at the tissue and cellular level in the infected host that have provided key insights on the phenotype, size, and characteristics of viral reservoirs and their local tissue microenvironments. Integration of unique, but complementary, imaging platforms that provide critical contextual insights into HIV reservoir biology with sensitive molecular and single cell approaches should prove instrumental in further promoting the development of new therapeutic strategies for sustained viral remission or elimination needed for an ‘HIV cure’ to be realized. MORE COLORFUL IMMUNOLOGY: TARGETED ISOLATION OF MONOCLONAL ANTIBODIES Mario Roederer ,NIH, Bethesda, MD, USA Monoclonal antibody (mAb) interventions for the prevention or treatment of HIV-1 infection have galvanized the field in the past five years. Broadly HIV- neutralizing mAbs are now being evaluated in clinical trials as therapeutics, “cure” strategies, and prophylaxis. The primary method of identification and isolation of these antibodies has been flow cytometric sorting of single cells, either based on antibody binding characteristics, or in bulk, from B cells of individuals infected or immunized with the antigens of interest. Optimization of this process has been undertaken on a wide range of fronts: probes (used to identify the B cells), immunophenotyping panels (to define particular subsets of interest), sorting speed and viability, post-sort culture or sequence identification (from single cells), highly sensitive micro-scale assays to define useful antibodies, cloning to express the antibody, and post-isolation improvements in affinity, solubility, manufacturability, and off-target effects. At the VRC, we built upon the successful isolation, optimization, and clinical development of VRC01 (now in Phase IIb testing HIV prophylaxis in 4,500 adults) to expand the repertoire of clinically-relevant antibodies for HIV, flu, malaria, and RSV, as well as testing interventions in preclinical primate models using SHIV or SIV. In this talk, I will review some of the types of screening technologies that we use to efficiently isolate novel, potentially clinical useful monoclonal antibodies. FELLOW TRAVELERS: INTERPRETING THE IMPACT OF THE MICROBIOME IN CLINICAL INTERVENTION Adam Burgener , Public Health Agency of Canada, Winnipeg, MB, Canada The microbiome represents the composition of bacteria, fungi, viruses, and their products that exist within the human body. It helps us digest food, shapes our immune system, and provides essential functions for human health. Many human diseases, including diabetes, inflammatory bowel disease, and cancer

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CROI 2019