CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

co-infections. While earlier initiation of ART appears to be beneficial in reducing the inflammatory state, and some commonly used medications with anti-inflammatory properties (e.g., statins) have shown some promise in pilot studies, there is a clear need for effective interventions to reverse persistent immune activation in this setting. These issues will become increasingly important as the HIV epidemic gets older, particularly in resource-limited settings, where the vast majority of HIV-infected individuals live. Yet, the most important pathways to target with novel interventions remain unclear. Conclusions: In the context of data being presented at CROI 2015, I will review key insights from observational studies and clinical trials that help characterize the scope of the problem of persistent immune activation in treated HIV infection. I will also highlight the importance of harnessing systems biology approaches in selecting optimal interventional targets and the need for pursuing these questions in both resource-rich and resource-limited settings. 5 HIV Cure Research John M. Coffin Tufts University, Boston, MA, US Background: Although current antiretroviral therapy suppresses HIV replication and halts the otherwise inevitable progression to AIDS, it is not curative. Even after a decade or more, its interruption leads inevitably to reappearance of the virus within a few weeks. These results imply the existence of a “reservoir” of HIV-infected cells capable of producing infectious virus that can reestablish active infection when antiviral drugs are no longer present. It is important to bear in mind that the true reservoir, as so defined, is a very small fraction of the total HIV-infected cells, which are stably present in individuals on therapy, of which the large majority harbor defective and whose properties may not be represented by the majority. At present, antiretroviral drugs have to be taken for life, an unsatisfactory situation due to expense, toxicity, and risk of failure. For these reasons, a major effort is underway worldwide to develop “curative” strategies that would allow cessation of therapy without return of the virus. The proof of concept that such a therapy might be possible is given by a single example: Timothy Brown, who was HIV infected and diagnosed with acute myeloid leukemia, and received 2 allogeneic bone marrow transplants from a donor whose cells were genetically defective in CCR5, and who is still HIV-free off treatment more than 5 years later. To date this experience has not been repeated, and several recent cases of sustained suppression off therapy have ended with the return of virus months to years later, so a true cure remains a distant goal, with many active lines of research directed at a number of specific, interrelated questions. 1. What is the nature and size of the reservoir? 2. How well do in vitro models of HIV latency reflect the in vivo situation? 3. Can we develop good animal models for latency and reactivation? 3. Can we reduce the reservoir size by activating expression of latent proviruses, relying on the virus or the immune system to kill the affected cell? 4. Can we “immunize” the individual (by immune or gene therapy strategies, for example) to prevent return of the virus after cessation of therapy? Conclusions: Despite recent advances in our understanding of hIV-1 latency as well as immunology and gene therapy, cure of HIV infection remains a distant goal. I will highlight new, exciting, and unexpected data on all of these issues and how they are advancing us toward that goal. 6 Martin Delaney Presentation: How to End the HIV Epidemic: Community Perspectives Steven F. Wakefield HIV Vaccine Trials Network, Seattle, WA, US Moderator: Steven F. Wakefield, HIV Vaccine Trials Network, Fred Hutch, Seattle, WA, USA Topics and Panel Members: Pre-exposure Prophylaxis (PrEP): Damon L. Jacobs, LMFT, New York New York, USA Treatment as Prevention (TasP): Connie L. Celum, MD, MPH, University of Washington, Seattle, WA, USA Cure-Related Research: Matt Sharp, Project Inform, San Francisco, CA, USA Background: The battle to end HIV has included the community-led safe sex movement in the 1980s, through lobbying for HIV treatments in the 1990s, to current efforts to achieve significant reductions in HIV transmission and cure research. In just over thirty years we’ve gone from “diagnosis = death” to “diagnosis =manageable infection” and for most, the prospect of a pretty normal lifespan. Advocacy and partnerships between communities and researchers has resulted in a sense an end is achievable. Conclusions: Each strategy to end the epidemic presents new information and opportunities for decisions about translating science into useful strategies. A licensed marriage/ family therapist / advocate from explains what it means to work with people in relationships. Noting that while trying to promote a sense of empowerment, and mental and spiritual health for people infected and affected with HIV there is need for help to negotiate the boundaries and agreements and how they discuss issues around sexuality, around sexual expression. A global health MD provides insight to trials regarding epidemiology about HIV and STIs, multi-center HIV prevention trials and the role of Treatment As Prevention (TASP) in combination community-level applications. An educator and service provider diagnosed with HIV in 1988 with a long history of advocating for AIDS treatment both participates in CURE research and teaches others to become subject matter experts on priorities, ethics and concerns as the scientific community finds a way forward.

Oral Abstracts

SessionW2Workshop

Room 6E

2:30 pm– 4:30 pm Clinical Trial Design and Analysis 7 Getting SMART About Innovative Designs for Studying Effectiveness: The Case of Adaptive Implementation Interventions Daniel Almirall University of Michigan, Ann Arbor, MI, US

The effective treatment and management of a wide variety of health disorders, including HIV/AIDS, often requires individualized, sequential decision-making. To do this, each patient’s treatment is dynamically adapted over time based on the patient’s history and changing disease state. Adaptive interventions (also known as dynamic treatment regimens) operationalize individualized decision making using a sequence of decision rules that specify whether, how, for whom, or when to alter the dose, type, or delivery of pharmacological, behavioral, and/or psychosocial treatments. Recently, there has been a surge of clinical and methodological interest in developing and evaluating adaptive interventions via clinical trials. Specifically, there is great interest in the use of sequential multiple assignment randomized trials (SMART), a type of multi-stage randomized trial design, to build high-quality adaptive interventions. The primary aim of this talk is to provide a brief, conceptual introduction on adaptive interventions and SMART designs. A secondary aim is to present the design and rationale of an example SMART which aims to develop a high-quality adaptive implementation interventions to improve the uptake/ adoption of an evidence-based intervention in community settings.

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CROI 2015