CROI 2019 Abstract eBook

Conference on Retroviruses and Opportunistic Infections Abstract eBook

Seattle March 4-7, 2019

Abstract eBook

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CONTENTS

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ABSTRACT PROCESS

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DISCLOSURE OF FINANCIAL RELATIONSHIPS WITH COMMERCIAL CONCERNS

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AUTHOR INDEX

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KEYWORD INDEX

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The contents of this Abstract eBook are current as of February 21, 2019. Please note that the contents may be periodically updated.

©Copyright 2019 CROI Foundation/IAS–USA. All rights reserved. ISBN # 978-1-7320053-1-0

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ABSTRACT PROCESS

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Scientific Categories A. Virology B. Pathogenesis: Human Studies and Animal Models C. HIV-Associated Tumor Viruses D. Host Immune Responses to Infection, Vaccines, and Immunotherapy E. HIV Reservoirs, Latency, and All Curative Strategies Including Therapeutic Vaccines and Gene Therapy F. Neuropathogenesis and Neurologic Complications G. Clinical Pharmacology H. Antiretroviral Therapy: Pre-Clinical Data, Randomized Trials, Efficacy and Effectiveness Studies I. HIV Drug Resistance J. HIV Diagnostics K. Hepatitis Viruses and Liver Complications L. AIDS-Related Malignancies M. Cardiovascular Complications of HIV Infection and Antiretroviral Therapy N. Other Complications of HIV Infection and Antiretroviral Therapy O. Tuberculosis and Other Opportunistic Infections P. Maternal and Fetal HIV Q. Pediatrics and Adolescents R. Epidemiology S. Testing T. Prevention Interventions U. Contraception, Sexually Transmitted Infections, and Reproductive Health V. Implementation and Scale-Up of Treatment and Care W. Population and Cost Modeling Abstract Content Author names, institutions, titles, and abstracts in the Abstract eBook and other materials are gernerally presented as submitted by the corresponding author. Abstract Review Process The PC and a panel of volunteer external reviewers reviewed more than 2000 submitted abstracts. Each abstract was reviewed by 5 to 10 reviewers selected for each abstract category based upon their individual expertise. PC members and external experts in the field reviewed the abstracts for the quality and originality of the work and scored them numerically. All reviewers were instructed to abstain from scoring any abstract on which they are an author or coauthor, have a financial or personal conflict of interest, or do not have the appropriate expertise to evaluate. Scores ranged from 1 (definite oral presentation) to 5 (rejected). Scores for each abstract were averaged and the standard deviation was calculated to assess variability. If variability was high, outlier scores were identified and censored. Abstracts with high variability in scores were discussed individually during a series of conference calls for each scientific category. Abstracts were accepted for oral presentations, for poster presentations, or rejected. Late-breaking abstract reviews included an assessment of the late-breaking nature of the work (distinct from a late submission).

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Embargo Policies and Social Media Research presented at CROI 2019 is embargoed until the conclusion of its presentation at the conference. Oral abstract presentations are embargoed until the conclusion of their presentation at the conference, or at an official CROI press conference, whichever comes first. Poster presentations are embargoed until the beginning of the poster session in which they are presented. CROI embargo policies apply to any public dissemination of research information presented at the conference, including electronic publications (eg, blogs) or social media (eg, Facebook, Twitter). No public dissemination of research information from the conference is permitted prior to the lifting of the conference embargo. Individuals or organizations that violate the conference embargo policy may have their conference credentials revoked and may forfeit the opportunity to participate in future conferences. Common Reasons for Abstract Rejection • Information is not new enough • Methodology is inadequate or insufficient to support conclusions • Background does not summarize the hypothesis • Submission is poorly written • Abstract is duplicative of other submissions • Submission reports clinical trial and data from unplanned analysis or incomplete or ongoing studies • Format does not follow guidelines (eg, section[s] missing, more than 1 graphic, table, or figure submitted) Statistics for Abstracts General abstract submitted . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1859 General abstracts accepted . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 992 General oral abstracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 General poster abstracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .900 Late-breaking abstracts submitted . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .189 Late-breaking abstracts accepted . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Late-breaking oral abstracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 Late-breaking poster abstracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Total abstracts submitted . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2048 Total abstract accepted . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1027 All Presenting Authors on Accepted Abstracts Region N Percent Africa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 . . . . . . . . . . . . . . . . 11 Asia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 . . . . . . . . . . . . . . . . . 2 Australia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 . . . . . . . . . . . . . . . . . 1 Europe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193 . . . . . . . . . . . . . . . . 21 Central and South America . . . . . . . . . . . . . . . . . . . . . 15 . . . . . . . . . . . . . . . . . 2 North America . . . . . . . . . . . . . . . . . . . . . . . . . . 584 . . . . . . . . . . . . . . . . 63 • Abstract is not appropriate for CROI • Controls are absent or inadequate • Statistical evaluation is inadequate or absent • Summary of essential results is inadequate or absent • Data are inadequate or insufficient to support conclusions

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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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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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trained and qualified to provide HIV testing and dispense PrEP, the so called “key population-led health services or KPLHS”, to around 50% of all Thai PrEP users. Four years after Thai Guidelines recommended PrEP, only 4% of 150,000 Thais at risk access PrEP. Government needs to de-medicalize PrEP and accept KPLHS roles in ending AIDS now. Over a decade, the world’s largest cohort (RV254) of 600 acute HIV cases has been established at TRC-AC. Through available routine NAT screening, early and frequent HIV testing has formed among certain populations. Immediate ART, together with extensive virologic/immunologic studies, demonstrated very low HIV reservoir even though there is no good news so far for HIV remission/cure. Crucial data for global HIV cure research are generated from Thailand although it is still too far away to get government’s attention. Achievements described is the outcome of continuing commitment of government, civil society, academics and royal family. Policy makers and politicians, who change frequently, are vital in the process since all successful pilot projects need to be scaled up. The country needs some influential ‘watch dogs’ to keep these strategies on track. Too much international appraisal can cause complacency among policy makers and politicians. 12 DENIAL, DOOM, OR DESTINY? RESURGENT STIs IN HIV CARE AND PREVENTION Jeanne M. Marrazzo , University of Alabama at Birmingham, Birmingham, AL, USA Antiretroviral therapy (ART) that achieves virologic suppression essentially eliminates the risk of sexual transmission to HIV-uninfected partners, informing the hope that treatment as prevention can play a major role in crippling the HIV epidemic. Moreover, persons who appropriately use preexposure prophylaxis (PrEP) can avoid HIV acquisition, and use of the currently approved agent, tenofovir-emtricitabine (TDF-FTC), is increasing globally. As uptake of these approaches has escalated, sexual behaviors have evolved on the different timelines that defined their implementation: first in people living with HIV as increasingly powerful ART reliably effected HIV suppression, then in people at risk for HIV as PrEP was rolled out. As ART enhanced quality of life and, naturally, sexual health, increases in rates of sexually transmitted infections (STIs) were reported among people living with HIV-notably syphilis, especially among men who have sex with men (MSM). This might be considered the “first new wave” of STIs in the post-ART era. As PrEP uptake has gained traction, a “second new wave” of increasing STI incidence has gathered strength, with record rates of gonorrhea and syphilis in MSM. The high efficacy of PrEP, especially in MSM, means that individuals at risk can avoid HIV acquisition in the absence of barrier methods of protection. Critically, MSM are not the only concern. In sub-Saharan Africa, PrEP is being rolled out in settings where syndromic management is still the standard approach to STI management-clearly, a suboptimal situation. Demonstration projects of PrEP in these settings have not had the capacity or intent to evaluate concomitant shifts in STI incidence at a community level. The implications of rising STI rates require reassessment of the alignment and prioritization of HIV research funding, health policy, and community engagement and inform numerous questions. Are STIs an inevitable byproduct of biomedical HIV control, and should the answer change our view of sexual health? Do we need to think differently about management of non-HIV STIs (screening, diagnosis, treatment, partner management) in those at risk for HIV? Is high STI incidence likely to undermine success of TasP or PrEP in the long term or in certain populations? Should new approaches focus on broader spectrum prevention (agents that inhibit HIV and other viruses)? What are the broad implications, including funding and trial design, for clinical STI research? From the outset of the HIV epidemic it became clear that the virus capitalized on the immune defenses of the host to create an immune environment that would further foster availability of cellular targets and viral replication. Several studies in animal models of SIV and in humans at various stages of disease have concluded that immune activation represents an independent prognostic factor in HIV including treated disease with successful virologic suppression. Systemic inflammation and immune activation in HIV have been linked to excess risk for both AIDS and non-AIDS serious events in both untreated and treated people living with HIV (PLWH), and seem to accelerate the detrimental effect of other comorbidities such as smoking or diabetes or aging. In addition, inflammation and cellular activation can be critical in viral persistence contributing to the preservation, expansion or population shifts of the HIV viral 13 INFLAMMATION: TAMING THE FLAMES Irini Sereti , NIAID, Bethesda, MD, USA

reservoirs. The etiology of immune activation and inflammation in treated HIV is considered multifactorial encompassing residual viral replication, mucosal injury at effector sites that leads to innate immune activation and potentially dysbiosis, incomplete CD4 restoration, tissue fibrosis and coinfections. Inflammation and fibrosis in HIV are also accompanied by coagulopathy. Biomarkers that signify the degree of inflammation such as IL-6, CRP, sCD14 as well as D-dimer levels have been found in numerous studies to be strong independent predictors of morbidity and mortality in PLWH. It is though unclear if and to what extent, altering these biomarkers with anti-inflammatory or other therapies could alter clinical outcomes. Efforts to counteract the chronic inflammation in HIV have focused on the various facets of its etiology largely with small or moderate success. At the moment the best approach is treatment with antiretroviral therapy, preferably at diagnosis at early stages of disease when CD4 counts are still high, in combination with aggressive treatment of possible comorbidities. A better understanding of the etiologic pathways and how they intersect leading to chronic inflammation in HIV will be critical for improved, and efficacious, treatment interventions. 14 HV VACCINE WITH LEEP DID NOT PREVENT RECURRENT CERVICAL HSIL IN HIV-INFECTED WOMEN Cindy Firnhaber 1 , Avril Swarts 2 , Masangu Mulongo 3 , Bridgette Goeieman 3 , Sophie Williams 3 , Simon Levin 3 , Mark Faesen 3 , Pamela Michelow 4 , Timothy Wilkin 5 1 University of Colorado, Aurora, CO, USA, 2 Clinical HIV Research Unit, Johannesburg, South Africa, 3 Right to Care, Johannesburg, South Africa, 4 National Health Laboratory Service, Johannesburg, South Africa, 5 Weill Cornell Medicine, New York, NY, USA Background: Women living with HIV are at high risk for cervical HSIL and rates are especially high in sub-Saharan Africa. These women have high HSIL recurrence rates after loop electroexcision procedure (LEEP) requiring additional monitoring and treatment. More effective treatment for HSIL lesions in HIV infected women is needed. Some retrospective studies suggest that the Human Papillomavirus (HPV) vaccine used as adjuvant therapy with LEEP improves response to treatment of High-grade Squamous Intraepithelial lesions (HSIL) in HIV negative women. We evaluated the effectiveness of the HPV quadrivalent vaccine in preventing the recurrence of HSIL after LEEP in HIV infected women in Johannesburg South Africa. Methods: We performed a double-blind, randomized clinical trial that enrolled 180 HIV infected women, between the ages of 18-65 years and cervical HSIL on histology in Johannesburg South Africa according to Consort criteria. The women were excluded if they were pregnant. Women received the quadrivalent HPV or placebo vaccine (1:1) at entry, week 4, and week 26. LEEP was performed at week 4. Colposcopy and directed biopsies and cervical cytology were performed at week 26 and 52. The primary endpoint was cervical HSIL by histology or cytology at either week 26 or 52, and this was compared between arms using Chi-square analysis. Results: Participant characteristics included median age 39, median CD4 489, and 94% had HIV suppression (<200 copies/ml) on antiretroviral therapy. Of the 180 women enrolled, 179 women underwent LEEP and 174 women completed the vaccine/placebo series and had evaluable results at week 26 or 52. The proportion experiencing the primary endpoint of HSIL was similar in the vaccine and placebo groups, 53% vs. 45% (RR 1.16, 95% CI .87-1.6, P=.29). Similar results were seen when using only histologic results at 26 and 52 weeks (32% vs. 31%, RR 1.04, 95% CI .67-1.04, P=.9). HSIL recurrence was associated with a LEEP result of HSIL and positive margins on LEEP at week 4. Conclusion: This randomized, double-blind clinical trial did not find evidence to support an adjuvant role for HPV vaccination for preventing recurrent HSIL post-LEEP in women living with HIV. Recurrent HSIL was high despite virologic suppression with antiretroviral therapy. More effective treatment strategies are needed to reduce the burden of recurrent cervical HSIL in this high risk population. 15 OPTIMAL LUNG CANCER SCREENING CRITERIA AMONG PERSONS LIVING WITH HIV Subhashini A. Sellers 1 , Andrew Edmonds 1 , Catalina Ramirez 1 , Sushma Cribbs 2 , Igho Ofotokun 2 , Laurence Huang 3 , Alison Morris 4 , Meredith C. McCormack 5 , Ken M. Kunisaki 6 , Maria P. Rivera 1 , M. Brad Drummond 1 , Adaora Adimora 1

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1 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2 Emory University, Atlanta, GA, USA, 3 University of California San Francisco, San Francisco, CA, USA, 4 University of Pittsburgh, Pittsburgh, PA, USA, 5 Johns Hopkins University, Baltimore, MD, USA, 6 Minneapolis VA Health Care System, Minneapolis, MN, USA Background: Based on the National Lung Screening Trial (NLST), US Preventive Services Task Force (USPSTF) recommends screening with low-dose chest computed tomography scan for adults aged 55-80 with >30 pack-year smoking history who are current smokers or quit within the last 15 years. Persons living with HIV (PLWH) are at increased risk for lung cancer but were excluded from the NLST. This study evaluated the performance characteristics of NLST criteria in confirmed lung cancer cases and matched controls from observational cohorts of men and women with HIV. We also explored alternative thresholds to improve lung cancer detection rates. Methods: We selected all confirmed lung cancers among PLWH who were current/former smokers and ≥40 years at diagnosis in the Women’s Interagency HIV Study (WIHS) and the Multicenter AIDS Cohort Study (MACS). Controls, selected from each cohort, were PLWH with no reported lung cancer during all follow-up visits, matched on 5-year age windows. Clinical and demographic characteristics, and proportions meeting NLST screening criteria, were compared. Alternative thresholds included iterative reductions in age, pack- years, and quit date. Results: We identified 44 WIHS women and 17 MACS men with HIV and incident lung cancer (Table). Lung cancer incidence was 270 and 104 per 100,000 person-years in women and men, respectively (p<0.001). Race and income did not differ between cases and controls. Compared to controls, women with lung cancer had a significantly lower median CD4 count but no significant difference in median viral load. In men, there were no significant differences in these markers of HIV infection between cases and controls. Only 16% of women and 24% of men with lung cancer met USPSTF screening criteria. Optimal age and pack-year screening criteria in women (age 49-75, ≥16 pack-year history) yielded 52% sensitivity and 75% specificity. In men, optimal criteria (age 43-75, >19 pack-year history) yielded sensitivity (82%) and specificity (76%). Conclusion: Current USPSTF lung cancer screening guidelines performed poorly in PLWH, as <25% of lung cancer cases met criteria. Alternative thresholds of age, smoking history, and quit date can better identify PWLH to screen for lung cancer. Among PLWH, lung cancer risk was higher in women than men. This study demonstrates the need for risk prediction modeling incorporating sex and markers of HIV infection to identify high risk individuals who would benefit from screening despite not meeting current USPSTF criteria.

1 Brigham and Women’s Hospital, Boston, MA, USA, 2 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 3 Botswana Ministry of Health, Gaborone, Botswana, 4 Life Gaborone Private Hospital, Gaborone, Botswana, 5 Massachusetts General Hospital, Boston, MA, USA, 6 University of Pennsylvania, Philadelphia, PA, USA, 7 Brigham and Women’s Hospital, Boston, MA, USA Background: Breast cancer is the second leading cause of cancer death among women living with HIV (WLHIV) with access to ART. In the context of ART coverage exceeding UNAIDS 90-90-90 targets, we sought to prospectively assess the impact of HIV on overall survival of women with breast cancer. Methods: As part of the Thabatse Cancer Cohort, we included women presenting (October 2010 to March 2018) for initial treatment of breast cancer at one of four oncology centers in Botswana. Consenting patients were interviewed, records abstracted, and followed for up to 5 years. The association between HIV infection and all-cause mortality was assessed using a multivariable Cox proportional hazards model including covariates selected a priori: cancer stage, curative versus palliative intent, receptor status, age, and personal income. Results: A total of 430 women with breast cancer with known HIV status were enrolled (4 women with unknown HIV status excluded), including 135 (31.4%) WLHIV and 295 (68.6%) uninfected women. WLHIV were younger than uninfected women, median 47.5 and 55.5 years, respectively (p<0.001). Among WLHIV, 110 (84%) were on ART prior to cancer diagnosis (median duration 6.8 years) and median CD4 count was 513 cells/μL. Advanced cancer stage (III/IV) was common for both WLHIV (67%) and uninfected women (66%). Immunohistochemistry results were available for 250 women (58%); 154 (62%) women were ER+ and 65 (26%) were triple-negative. Receptor status was similar by HIV status (p=0.89). The majority (69%) received multimodality treatment with curative intent and the proportion did not differ by HIV status (p=0.80). After 847 patient-years of follow-up, 156 women died, including 66 (49%) WLHIV and 90 (31%) uninfected women. Three women (0.7%) were lost to follow-up. The majority of deaths (141, 90%) were attributed to cancer and none to HIV. Two-year survival for WLHIV was lower than those without HIV, 57% and 73%, respectively (see Figure, p<0.001). Findings were similar in adjusted analyses with WLHIV experiencing higher mortality (hazard ratio 1.86, 95%CI 1.33 to 2.61, p<0.001). Cancer stage, treatment intent, and personal income less than $50/month were also inversely predictive of survival (p<0.001 for each). Conclusion: HIV infection is associated with substantially higher non-AIDS mortality among women with breast cancer. Improved understanding of mechanisms underlying excess mortality could contribute to improved outcomes in the majority female and aging African HIV epidemic.

Oral Abstracts

16 HIV IS ASSOCIATED WITH DECREASED BREAST CANCER SURVIVAL: A PROSPECTIVE COHORT STUDY Katrin S. Sadigh 1 , Ryan M. Hodgeman 2 , Neo Tapela 3 , Isaac Nkele 2 , Memory Bvochora-Nsingo 4 , Sebathu Chiyapo 4 , Tlotlo B. Ralefala 3 , Jason A. Efstathiou 5 , Oaitse John 2 , Galaletsang Motswetla 2 , Surbhi Grover 6 , Jerry Younger 5 , Mompati O. Mmalane 2 , Shahin Lockman 7 , Scott Dryden-Peterson 7

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17 LONG-TERM OUTCOMES OF 58 PATIENTS WITH HIV AND KSHV+ MULTICENTRIC CASTLEMAN DISEASE

individuals or immune suppressed transplant patients. The prevalence for both KSHV and KS are highest in sub-Saharan Africa where HIV-1 infection is also epidemic. Current therapies for KS are not effective, with high reoccurrence and mortality rate. Similar to other herpesviruses, KSHV’s ability to establish latency in the host presents a major challenge to KS treatment or prevention. Among KSHV genes, the latency-associated nuclear antigen (LANA) is absolutely required for latency. Hence, strategies to eliminate LANA from KSHV latently infected cells might lead to prevention or treatment of KS. Methods: We designed a replication-incompetent adenovirus to deliver LANA- specific CRISPR-Cas9 system (Ad-CC9-LANA) at high efficiency into various KSHV latently infected cells and monitored over a period of 32 days. The effects of Ad- CC9-LANA had on KSHV episome in latently infected cells were then determined by droplet digital PCR. Real-time PCR was utilized to measure the mRNA expressions for LANA and Cas9. Immunohistochemistry (IHC) was performed to demonstrate the reduction of KSHV latently infected cells in Ad-CC9-LANA transduced cultures. Results: Reduction in KSHV episome was evidence as early as 4 days of transduction by Ad-CC9-LANA. At 32 days post-transduction, the Ad-CC9-LANA transduced cultures demonstrated a substantial reduction in KSHV episome copy number in latently infected cells. These reductions were accompanied by decrease in the LANA mRNA expression and confirmed by IHC. These observations were not due to cell death due to adenovirus transduction as demonstrated by the similar growth kinetic between transduced and non- transduced cells. The Cas9 mRNA expression was also shown to be robust and detected throughout the study period. Conclusion: Our study demonstrated the feasibility of using a KSHV LANA- targeted CRISPR-Cas9 system to disrupt KSHV latency in infected epithelial and endothelial cell lines. This approach to limit KSHV latency may also represent a viable strategy for against other tumorigenic viruses such as HCV, HPV and EBV. Therefore, it will have significant benefits to human health worldwide and particularly in developing countries where the viral cancer burden is high. 19 THE ROLE OF WILMS' TUMOR 1 IN KAPOSI SARCOMA HERPESVIRUS ONCOGENESIS Ayana Morales 1 , Ethel Cesarman 1 , Paul Rubinstein 2 , Warren Phipps 3 1 Weill Cornell Medicine, New York, NY, USA, 2 Rush University Medical Center, Chicago, IL, USA, 3 University of Washington, Seattle, WA, USA Background: Kaposi Sarcoma (KS), caused by HHV-8, is the most common HIV associated malignancy globally. It occurs predominantly in sub-Saharan Africa where it has a high mortality rate. Despite the burden of KS, it is unknown if KSHV causes a reactive proliferative process or a clonal malignancy due to oncogenic genetic alterations that occur in latent infection due to genetic instability. Discovery of recurrent genetic alterations would provide an improved understanding of KS pathogenesis and may allow for the development of prognostic biomarkers and improved treatment options. A promising cancer antigen is WT1 (Wilms’ Tumor 1), for which WT1 therapeutic vaccines have demonstrated benefit in patients with leukemias and solid tumors, and has served as a prognostic marker in patients with myelodysplastic syndromes and leukemias. Different isoforms of WT1 are proposed in leukemias and in solid tumors to have both tumor suppressive and oncogenic roles. We propose that genetic alterations of WT1, a preliminary finding among a subset of KS patients play a role in KS tumorigenesis. Methods: KS biopsy samples are obtained fromWeill Cornell Medical College, Stroger Hospital in Chicago and from the HIPPOS study (Kampala, Uganda). Lentiviral transduction of WT1 shRNA of KSHV infected 293T and endothelial cells were used to explore the role of identified genetic alterations. Results: We identified a deletion of WT1 in 2/11 patients with KS. Loss was confirmed by immunohistochemistry in these cases, while WT1 overexpression was seen in non-mutated cases. In an expanded cohort, we found additional cases that overexpress WT1 while others had no expression. In addition, the ‘tumorigenic’ form, cugWT1, was upregulated in endothelial and 293T cells upon infection with KSHV. Similar to the role of the oncogenic form of WT1 in other cancers in regulation of secondary target genes, knockdown of WT1 decreased BCL-2 expression, an anti-apoptotic gene. Conclusion: Kaposi sarcoma may manifest along a spectrum, as an inflammatory lesion or as a clonal malignancy, due to transformation in the setting of chronic KSHV infection leading to genomic instability. Given the finding of WT1 deletions in a subset of cases, as well as overexpression in others, WT1 isoforms may have pro-oncogenic and tumor suppressive roles in KS. Our

Ramya Ramaswami , Kathryn Lurain, Priscila H. Gonçalves, Mark Polizzotto, Anaida Widell, Matthew Lindsley, Richard F. Little, Thomas S. Uldrick, Robert Yarchoan NIH, Bethesda, MD, USA Background: Multicentric Castleman disease (MCD) is a rare systemic lymphoproliferative disease caused by Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpes virus 8 (HHV-8). Patients with HIV and KSHV-MCD may also have Kaposi sarcoma (KS) and are at increased risk of developing non-Hodgkin lymphoma, especially primary effusion lymphoma (PEL). The historical overall survival was 2.5 years, but this has improved following the use of rituximab for KSHV-MCD and antiretroviral therapy for patients with HIV. Here, we present the long-term outcomes of the largest prospective study of KSHV-MCD and HIV+ patients in North America. Methods: We evaluated longterm outcomes and concurrent diagnoses (KS and PEL) that influenced overall survival for patients with HIV and KSHV-MCD in a natural history study with 5 optional treatment regimens for MCD flares. This included high-dose zidovudine and ganciclovir, sirolimus, rituximab (R) with liposomal doxorubicin (R-LD) followed by interferon-α or high-dose zidovudine with valganciclovir (AZT/VGC), or rituximab plus infusional chemotherapy (R-EPOCH). Results: There were 58 participants (54 male, 4 female) with a median (range) age of 44 years (26-68), HIV VL <50 copies/mL (50 – 64100) and CD4 count 180 cells/μL (3-1319) at MCD diagnosis. All patients were on combined antiretroviral therapy at study entry, 38 patients had received prior therapy for KSHV-MCD (18 patients with R-based therapy), and 39 patients had a concurrent diagnosis of KS. Nine patients (15%) developed PEL after entry and 1 patient had been diagnosed with PEL prior to KSHV-MCD. Patients diagnosed with PEL were treated with R-EPOCH. The median duration of follow up was 4.1 years. Of the treatment options available in this study, the majority (52 patients (89%)) received R-LD, usually followed by high-dose AZT/VGC. The 5-year overall survival was 80% (95% confidence interval (CI), 66% to 88%). Eleven patients died: 4 from PEL, 4 from KSHV-MCD and associated complications, 2 from KS and sepsis, and 1 died from pancreatic cancer. A concurrent diagnosis of KS was not clearly a prognostic factor (hazard ratio (HR) 2.4; 95% CI, 0.5-11.1, P=0.3). However, a coexistent diagnosis of PEL was associated with worse survival (HR 3.4; 95% CI, 0.99-11.6, P=0.05, figure 1). Conclusion: KSHV-MCD is an under diagnosed but highly treatable condition if recognized. Physicians need to identify and promptly treat concurrent diagnoses of PEL and KS that may contribute to morbidity and mortality.

Oral Abstracts

18 REDUCTION OF KAPOSI SARCOMA–ASSOCIATED HERPESVIRUS LATENCY USING CRISPR-CAS9 For Yue Tso , John T. West, Charles Wood University of Nebraska–Lincoln, Lincoln, NE, USA Background: Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), an AIDS defining cancer in HIV-1 infected

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data suggest that two types of KS exist, based on loss or overexpression of WT1. In KS cases that overexpress this protein, WT1 may be a promising target as a biomarker and immunotherapy.

in point-of-care format, and ultimately greatly increase access to timely and accurate KS diagnosis.

Oral Abstracts

20LB QUANTIFICATION OF KSHV DNA AS A DIAGNOSTIC TEST FOR KAPOSI SARCOMA IN AFRICA Aggrey Semeere 1 , Andrea Gardner 2 , Megan Wenger 3 , Priscilla Namaganda 1 , Ryan Snodgrass 4 , Varun Kopparthy 4 , Esther Freeman 5 , John Ssali 6 , Mwebesa Bwana 7 , Toby Maurer 3 , Robert Lukande 8 , Miriam Laker-Oketta 1 , David Erickson 4 , Ethel Cesarman 2 , Jeffrey Martin 3 1 Infectious Disease Institute, Kampala, Uganda, 2 Weill Cornell Medicine, New York, NY, USA, 3 University of California San Francisco, San Francisco, CA, USA, 4 Cornell University, Ithaca, NY, USA, 5 Massachusetts General Hospital, Boston, MA, USA, 6 AIDS Healthcare Foundation Uganda, Kampala, Uganda, 7 Mbarara University of Science and Technology, Mbarara, Uganda, 8 Makerere University College of Health Sciences, Kampala, Uganda Background: Histopathologic evaluation, the gold standard for diagnosis of Kaposi sarcoma (KS), has long been limited in sub-Saharan Africa by lack of personnel and materials. Even where pathology is available, accuracy of KS diagnosis is often sub-optimal. This has led to widespread delays and inaccuracies in KS diagnosis, often resulting in late or improper treatment (e.g., unwarranted chemotherapy). As an alternative to histopathology, we hypothesized that quantification of KSHV DNA in skin lesions can diagnose KS. Methods: We evaluated consecutive patients with skin lesions, suspected by their primary care providers to be KS, who were referred for a skin biopsy at 3 HIV care centers in Uganda. Traditional histopathologic evaluation of the 5 mm skin punch biopsies, including anti-LANA staining, was performed in Africa and by up to 3 pathologists in the US. Quantitative PCR (qPCR) for KSHV ORF 26 was performed on extracted DNA from the biopsy. Using the consensus of the US pathologists as the gold standard, we determined the sensitivity & specificity of PCR (both qualitative and quantitative) for KS diagnosis. A receiver operating characteristics curve was used to assess quantitative cutpoints and area under the curve (AUC). Results: We tested 506 participants with skin lesions. Median age was 33 years, 38%were women, and 94%were HIV-infected; 22% of lesions were macules, 64% plaques, and 14% nodules. Consensus US pathologic testing revealed that 330 biopsies were KS, 149 not KS and 27 were indeterminate. Using US pathology as gold standard, the sensitivity of African pathology was 95% and specificity was 70%. Sensitivity of qualitative detection (presence or absence) of KSHV DNA for KS diagnosis was 99% but specificity was only 78%. Evaluation of quantitative KSHV DNA content found an AUC of 0.96; at the optimal cutpoint (1412 KSHV copies per 5 µl specimen), sensitivity was 98% and specificity was 90%, with 96% of subjects correctly classified. Conclusion: In the context of sub-Saharan Africa, where KSHV is endemic, quantification of KSHV DNA content in skin lesions by PCR has both high sensitivity and specificity for the diagnosis of KS when compared to gold standard pathology. In contrast, qualitative detection of KSHV DNA is non- specific. The findings suggest that a nucleic acid amplification-based diagnostic test for KS could largely replace the need for histopathology, be implemented

21 TWO NOVEL POTENTIAL THERAPEUTIC TARGETS IN THE KSHV LIFE CYCLE Thomas Schulz , Medizinische Hochschule Hannover, Hannover, Germany Twenty-five years after the discovery of KSHV our understanding of the molecular mechanisms governing its replication, persistence and pathogenicity has advanced to the point where it may become possible to identify novel therapeutic targets for pharmacological intervention. In our recent work, we have focused on the KSHV thymidine kinase and a non-structural membrane protein encoded by open reading frame (ORF) K15. Work by Gill and colleagues (EMBO J. 2014) had suggested that the KSHV thymidine kinase (TK) homologue, encoded by ORF 21, has tyrosine kinase properties. We therefore explored if tyrosine kinase inhibitors already approved for cancer chemotherapy would show activity against KSHV TK. We found that several compounds potently inhibit KSHV TK in in vitro and ex cellulo kinase assays, and also strongly inhibit KSHV productive (lytic) replication in tissue culture, as well as KSHV-dependent tumorigenesis in a xenograft model. Regarding the viral non-structural membrane protein encoded by ORF K15 (pK15), we have previously shown that is expressed in Kaposi Sarcoma tissue and that, in primary endothelial cells, it is required for KSHV-dependent angiogenic and proliferative effects, as well as for the ability of KSHV to reactivate from latency; pK15 recruits, and promotes the activation of, the cellular lipase PLC ϒ 1 to achieve these biological properties (Bala et al., PLoS Path. 2012; Gramolelli et al., PLoS Path 2015; Abere et al. PLoS Path. 2017; Abere et al. J. Virol. 2018). We have now studied the interaction of pK15 with PLC ϒ 1 at the molecular and structural level and identified first small molecule inhibitors that potently interfere with the activation of PLC ϒ 1 by pK15 and KSHV lytic replication. Ongoing work aims to optimize these ‹hits› to reach a starting point for hit-to-lead development. 22 TARGETING THE NONCANONICAL NF- κ B PATHWAY REVERSES SIV LATENCY Maud Mavigner 1 , Richard M. Dunham 2 , Alyssa Brooks 1 , Cristin Galardi 3 , Gavin C. Sampey 4 , Steven E. Bosinger 5 , Thomas Vanderford 5 , David M. Margolis 4 , Guido Silvestri 5 , Ann Chahroudi 1 1 Emory University, Atlanta, GA, USA, 2 GlaxoSmithKline, Research Triangle Park, NC, USA, 3 ViiV Healthcare, Research Triangle Park, NC, USA, 4 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 5 Yerkes National Primate Research Center, Atlanta, GA, USA Background: The leading approach to eradicate HIV consists of the induction of latency reversal and subsequent clearance of cells reactivating the virus. Here, we tested a novel latency reversing agent (LRA) strategy that selectively activates the non-canonical NF-κB pathway (ncNF-κB) using a mimetic of the second mitochondrial-derived activator of caspases (SMACm). Methods: We evaluated the SMACm AZD5582 in 12 SIV-infected ART- suppressed rhesus macaques (RM) compared to 9 controls. After over a year of ART, RM received 3-10 weekly doses of AZD5582 intravenously at 100 μg/ kg. Plasma viral loads (PVL) were measured longitudinally and levels of cell- associated SIV-RNA and -DNA were quantified in resting CD4+ T-cells isolated from peripheral blood, lymph nodes (LN), spleen and bone marrow (BM).

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