CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

ORAL ABSTRACTS

MONDAY, FEBRUARY 23, 2015 SessionW1Workshop

Room 6E

9:00 am– 12:30 pm Program CommitteeWorkshop for New Investigators and Trainees 1 A Path to an HIV Vaccine Galit Alter Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, US

Background: Despite our growing antiviral armamentarium and our clear appreciation on how HIV infection may be blocked, HIV continues to spread like wildfire in some communities globally. Thus a vaccine is desperately needed. The HIV vaccine community has experienced renewed optimism over the past decade due to: 1) our growing appreciation for novel unexpected immune correlates of infection in the RV144 vaccine trial that showed moderate protection from infection, as well as 2) our growing capacity to identify and mechanistically profile novel neutralizing antibodies with remarkable antiviral potency. However, despite these advances, to date, it is still incompletely understood how such responses can be induced via vaccination, or how they emerge naturally during infection. Conclusion: This presentation will therefore highlight our current understanding of the immunological profile of “protective” anti-HIV immunity, will review the “rational” vaccine design strategies that are being exploited in the vaccine field, as well as dissect the unexplored and untapped research opporutinities in the field. Throughout the presentation, information will be provided on where and when the latest information will be presented at CROI. 2 Animal Models of HIV Prevention and Cure Guido Silvestri Emory University, Decatur, GA, US While the availability of very potent anti-retroviral therapy (ART) regimens has dramatically reduced the mortality and morbidity associated with HIV infection, the absence of a safe and effective AIDS vaccine and the inability to eradicate or functionally “cure” the infection remain major challenges in contemporary HIV/AIDS research. In this context, basic and translational research in the areas of HIV pathogenesis, prevention, and therapy has long benefited from the availability of animal models that allow the in vivo testing of novel conceptual hypothesis and intervention strategies that would be virtually impossible to test in humans. The key animal models for HIV infection are non-human primates (NHP) such as Asian macaques, that have been extensively used in studies of candidate AIDS vaccines, and natural SIV hosts, such as sooty mangabeys and African green monkeys, that have been extensively used for comparative studies of AIDS pathogenesis. More recently several types of so-called humanized mice have been developed to allow in vivo studies of the interaction between HIv and the human immune system. It must be emphasize that NHP and humanized mice represent highly synergistic models that, far from being alternative to each other, are in fact each better suited to answer specific scientific questions, and therefore should be used, ideally, as complementary aspects of comprehensive experimental strategies. In this presentation, I will briefly review the opportunities presented by the various NHP and humanized mice models to conduct studies that will improve our understanding of AIDS virology, immunology, and pathogenesis, with specific focus on studies of HIV vaccines and eradication, including those that will be presented at CROI 2015. We hope that, ultimately, pre-clinical in vivo studies in NHPs and humanized mice will inform the design of novel prevention and therapeutic strategies for HIV infection in humans. 3 HIV Prevention 2.0: What’s Next? Susan P. Buchbinder San Francisco Department of Public Health, San Francisco, CA, US Background: For the first 30 years of the HIV epidemic, the 3 pillars of the prevention of sexual HIV transmission focused on HIV education, testing, and condoms. These interventions, tied to community mobilization campaigns, led to dramatic declines in HIV transmission in many communities. Substantial disparities remain in HIV incidence in vulnerable populations, particularly among men who have sex with men globally, and young women in sub-Saharan Africa. However, the last few years have demonstrated that antiretrovirals can serve as powerful prevention tools – both for blocking transmission from treated HIV infected persons and blocking acquisition for HIV-uninfected persons on pre-exposure prophylaxis (PrEP). The pillars of this second generation of HIV prevention include better HIV testing strategies; scale-up of treatment as prevention; and new PrEP agents, schedules, and delivery systems. The HIV prevention pipeline now includes many new drug formulations (including long-acting injectables and vaginal rings), some of which have reached late stage testing. Phylogenetic studies are uncovering important clues about transmission networks, and modeling studies are demonstrating reasons for ongoing disparities within vulnerable populations. We anticipate results of several pivotal trials will be available in 2015. Conclusions: We are poised to enter the 3 rd major stage of HIV prevention, combining treatment as prevention and PrEP synergistically to “turn the curve” on new HIV infections and their sequelae. Challenges in achieving high HIV prevention and treatment uptake, adherence, and retention remain; addressing these gaps is a current research priority. 4 Pathogenesis of HIV Complications Peter W. Hunt University of California San Francisco, San Francisco, CA, US Background: While HIV-infected individuals with access to modern antiretroviral therapy (ART) have experienced a dramatic improvement in life expectancy, they remain at higher risk than the general population for morbidity and mortality, particularly from non-AIDS complications typically associated with aging. While lifestyle factors (e.g., smoking, illicit drug use, obesity, etc) as well as ART toxicities likely play a role, it is now well recognized that abnormal immune activation and inflammation persist in many ART-suppressed individuals, including those that restore normal CD4+ T cell counts, and that the extent of these immunologic defects strongly predicts morbidity and mortality from non-AIDS conditions. Multiple causes of the persistent inflammatory state have been proposed including HIV persistence, microbial translocation, CMV and other prevalent

Oral Abstracts

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CROI 2015