CROI 2020 Abstract eBook

Abstract eBook

Oral Abstracts

ORAL ABSTRACTS

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SESSION OVERVIEW: 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 Over the past four decades, remarkable progress has been made in understanding HIV epidemiology, pathogenesis, treatment, and prevention from the combined efforts of community members, clinicians, investigators, and funding agencies worldwide. Yet more work and new approaches are needed to achieve the ambitious goal of ending the epidemic and ensuring optimal quality of life for those living with HIV. To encourage and stimulate the next generation of investigators, the CROI Program Committee organizes an annual Workshop for New Investigators and Trainees comprised of expert and comprehensible talks to cover current knowledge and controversies in basic, clinical and public health investigation into HIV and related infections, and to highlight relevant work to be presented over the ensuing days at CROI. This year’s Workshop will begin with Dr. Wes Sundquist who will review aspects of HIV-1 replication and innate immunity, in particular recent developments in our understanding of mechanisms of virus sensing, early steps in the viral replication cycle, and virus-host arms races. Dr. Richard Koup will cover recent preclinical HIV vaccine advances, concentrating on efforts to induce either broad neutralizing antibody responses or protective CD8 T cells, and discuss the latest data on the development and use of broadly neutralizing antibodies in prevention and treatment of HIV. Dr. Hermione Lyall will review ongoing challenges in prevention of vertical HIV transmission during pregnancy and breastfeeding, short and long term challenges of getting infants on to treatment, and approaches to sustaining health and supporting ‘undetectable=untransmittable’ in youth with HIV. Dr. Susan Buchbinder will describe the current status of new infections globally, and discuss recent advances in biomedical HIV-1 prevention including treatment as prevention, pre-exposure prophylaxis, topical preventive agents, HIV vaccines, and combination approaches to HIV prevention. Finally, Dr. Nicolas Chomont will review the mechanisms that contribute to HIV persistence during ART, highlight the role of cell proliferation in that process and present recent therapeutic approaches aimed at curing HIV infection. The Workshop serves as the initial opportunity for Trainees and New Investigators to interact with Program Committee members. Such interactions will continue during newmorning sessions organized to provide support and guidance for emerging investigators at this year’s CROI. SHIFTING FROM ACUTE TO CHRONIC, AGING, LONGEVITY, AND LIVED EXPERIENCE Jim Pickett 1 , Martha Tholanah 2 , Gabriel Maldonado 3 , Celeste Watkins-Hayes 4 1 AIDS Foundation of Chicago, Chicago, IL, USA, 2 Advocate, Harare, Zimbabwe, 3 TruEvolution, Riverside, CA, USA, 4 Northwestern University, Chicago, IL, USA Globally, there were 5.7 million [4.7 million– 6.6 million] people living with HIV (PLHIV) 50 years of age and older (50+) in 2016. Although the proportion of PLHIV50+ was greater in high-income countries, low-and-middle-income countries have higher numbers of PLHIV50+ that are expected to continue to increase by 2020. The proportion of PLHIV50+ across the world increased substantially from 8% in 2000 to 16% in 2016 and is expected to increase to 21% by 2020*. In the United States, it is estimated that more than 70% of PLHIV will be 50 or older in 2020. Thirty-nine years into the epidemic, we’ve seen a remarkable shift in the trajectory of HIV. No longer is an HIV diagnosis simply a death sentence, individuals with HIV are living longer than ever before. Issues related to aging, long ignored due largely to irrelevance, are coming to the fore. What does it mean to age with HIV across the lifespan? How do co-morbidities, polypharmacy, long-term adherence to medications, mental health, neurocognitive impairment, stigma, discrimination, and fatigue factor into long-term survival? How do resilience and other mechanisms shift the narrative from surviving to thriving? What factors must be considered beyond viral

suppression when assessing the quality of life? Each panelist will share their distinctive perspectives and experiences and will then open up the discussion to include audience members. * Global and regional trends of people living with HIV aged 50 and over: Estimates and projections for 2000–2020, PLoS One. 2018; 13(11): e0207005.

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SHAPING VACCINES WITH DNA ORIGAMI Mark Bathe , MIT, Cambridge, MA, USA

Viral-like structured DNA and RNA assemblies, also known as DNA and RNA origami, offer the ability to co-formulate gene-length single-stranded DNA or mRNA with CRISPR-RNPs, siRNAs, or ASOs, with the integration of active cellular targeting, stimulation, and uptake moieties including peptides, sugars, and small molecules. Biological stability and immunostimulation can additionally be programmed selectively through the use of chemical modifications. Scaleable bacterial production of custom length and sequence single-stranded DNA offers a low-cost path towards clinical-scale production. Here, I will present our lab’s formulation and preclinical work in the context of the field, to produce pre- clinical scale, endotoxin-free structured DNA and RNA assemblies for targeted delivery of nucleic acid gene therapeutics and vaccines, including a case study of viral-like DNA assemblies applied to an HIV vaccine candidate. CONCEPTS IN RESERVOIR MEASUREMENTS Janet M. Siliciano , Johns Hopkins University School of Medicine, Baltimore, MD, USA A stable latent reservoir for HIV-1 in resting CD4+ T cells precludes cure. Curative strategies targeting the reservoir are being tested and require accurate, scalable reservoir assays. The reservoir was originally defined with a quantitative viral outgrowth assays (QVOA) for cells releasing infectious virus following one round of T cell activation. This assay requires growing virus from individual latently infected cells and is costly and time consuming. Therefore, many studies have used DNA PCR to detect HIV-1 proviruses in infected cells or RT-PCR to detect the induction of viral RNA production from latently infected cells. However, two fundamental findings have altered how we view reservoir measurements. The first is that the vast majority of HIV-1 proviruses are defective due to the presence of large deletions and/or APOBEC-mediated hypermutation, as revealed by near-full genome proviral sequencing. These defective proviruses cannot contribute to viral rebound and should not be considered part of the latent reservoir. Most PCR assays fail to distinguish intact and defective proviruses. Therefore, they dramatically overestimate reservoir size and should not be used. The second important finding is that not all intact proviruses are induced by a single round of in vitro T cells activation. Therefore, induction assays that measure viral outgrowth or viral RNA production after a single round of T cell activation will underestimate reservoir size. A conceptually novel approach to measuring the latent reservoir is to count all of the intact proviruses regardless of their transcriptional status at any particular time. This can be done with the intact proviral DNA assay (IPDA). More recently identified conceptual issues in reservoir measurement include the problem of clonal expansion. The reservoir is dominated by large clones of infected cells that wax and wane over time, and current measurements do not capture dynamic changes in reservoir composition. In addition, the relationship between the viruses that cause rebound following interruption of antiretroviral therapy and the viruses detected in various reservoir assays needs to be clarified. This talk will discuss these issues and summarize the current state of reservoir measurements. The HIV replication cycle includes integration of the reverse-transcribed viral genome into the host cell DNA where the provirus is retained for the life of the cell. Cellular machinery is used for proviral genetic expression, however, by means that are not fully understood, some HIV proviruses can maintain a latent, or transcriptionally-silent, state. It is thought that cells expressing HIV are susceptible to cell killing by cytopathic effects or immune responses. It stands CHARTING GENOME-WIDE INTEGRATION Mary F. Kearney , National Cancer Institute, Frederick, MD, USA

Oral Abstracts

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CROI 2020