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NHLBI AIDS Working Group: Advancing HIV/AIDS Research in Heart, Lung, and Blood Diseases

Executive Summary


September 6-7, 2012, Bethesda, MD

Tremendous progress in the treatment of HIV/AIDS has led to increased survival. As a result, by the year 2015 more than half of all patients with HIV in the United States will be age 50 years or older. Although advances in therapy have led to increased longevity, the HIV population is now experiencing a host of chronic diseases associated with aging, such as cardiovascular (CV), lung, and blood disease. In addition, in patients with HIV, there may be a complex interplay among inflammation, traditional risk factors, and the adverse effects of anti-retroviral therapy that may contribute to end-organ complications.

The National Heart, Lung and Blood Institute (NHLBI) convened a Working Group (WG) on September 6-7, 2012 in Bethesda, MD to address emerging research priorities in non-infectious HIV-related heart, lung, and blood disease. The WG was composed of basic and clinical researchers with HIV, CV, pulmonary, and hematologic scientific expertise. The WG was designed as the launching point for the next phase of the NHLBI AIDS program, and the primary aim of the meeting was to elicit recommendations that would inform the future goals and strategic plan of the NHLBI AIDS program. To achieve this goal, WG participants were asked to develop: 1) recommendations on the top scientific priorities in HIV-related heart, lung, and blood disease, as well as blood-based therapies (hematopoietic stem/progenitor cell-based transplants, T cells); 2) strategies to enhance dialogue and collaboration among different scientific communities; 3) approaches on how to leverage existing research resources; and, 4) ideas on how to successfully implement research in HIV-related heart, lung, and blood disease.

The WG included multi-disciplinary sessions during which cross-cutting challenges about developing the field were addressed, as well as heart, lung, and blood break-out sessions during which disease-specific issues were discussed. Break-out sessions used a case study approach and key questions were used in each group to catalyze discussion. The heart session focused on HIV-related atherosclerosis/coronary artery disease (CAD), the lung session centered on HIV-related chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH), and the blood session addressed HIV-related anemia and the role of hematopoietic stem and progenitor cells both as potential reservoirs and as potential cures for the disease. WG participants were asked to identify the highest priority research gaps within these areas and recommend future research strategies to address those gaps. Although the WG included experts from multiple disciplines and varied backgrounds, common themes about scientific priorities and strategies to optimize research emerged in all three groups.

Scientific Themes

The top scientific priorities in each of the three break-out groups focused on epidemiology, pathogenesis, and the prevention and treatment of HIV-related heart, lung, and blood disease and the potential use of cellular/gene therapies to eradicate HIV. The scientific recommendations are presented in the tables below and are categorized by the topics addressed in each break-out session.

Heart

Epidemiology

Scientific Gaps

Approaches to Gaps

  • Incidence/prevalence of CAD in patients with HIV
  • Interplay of HIV, inflammation, anti-retroviral therapy, co-infections, and traditional risk factors on development of CAD
  • Consolidate current knowledge through reviews and meta-analyses
  • Utilize current HIV and CV studies to examine questions about HIV-related CAD
  • Add or adjudicate CV events (CAD, venous thrombosis, pulmonary embolism) in HIV cohort studies to detect general trends by leveraging cohorts with large numbers of HIV patients
  • Enrich CV cohort studies with rigorously collected CV data with HIV patients to allow for a detailed assessment of CAD rates and the relative contribution of traditional and HIV-specific risk factors on the development of CAD
  • Examine long-term outcomes and determinants of outcomes following CV events
  • Conduct studies evaluating HIV-related CV disease in women and minorities, and address health disparities

Pathophysiology

Scientific Gaps

Approaches to Gaps

  • Mechanisms of the interplay of HIV/inflammation, anti-retroviral therapy, co-infections, and traditional risk factors in development and progression of CAD
  • Need for better animal and molecular models
  • Characterization of atherosclerotic plaque in HIV patients through CV imaging (angiography, CT angiography, magnetic resonance imaging)
  • Combine pre-clinical development of resources with hypothesis generating research
  • Expand the use of animal models to explore the relationship between virally-mediated inflammation and atherosclerosis
  • Enrich imaging studies (such as those focused on angiography, CT angiography, magnetic resonance imaging) with HIV patients
  • Conduct mechanistic and imaging studies that elucidate the pathogenesis of CAD in HIV patients

Prevention and Treatment

Scientific Gaps

Approaches to Gaps

  • Potential differences in the prevention and treatment of CAD in HIV patients
  • Actual efficacy and effectiveness of evidence-based CV therapies in HIV patients
  • Appropriate targets for therapy in HIV patients
  • Novel therapies to address unique pathophysiology of CAD in HIV patients
  • Add CV outcomes to HIV trials to understand the effects of HIV therapies on CAD
  • Increase enrollment of HIV patients into CV trials – to understand efficacy with larger sample sizes and safety with smaller subgroups
  • Collaborate with HIV trial networks early during protocol development to address CV questions
  • Conduct novel pilot trials in HIV-related CAD
  • Develop best practices to incorporate HIV testing into clinical trials
  • Leverage existing CV databases, claims data, and electronic health records to evaluate CV patterns of care, and variation in prevention, diagnosis, and treatment of CAD, medication adherence, post-event outcomes, and implementation of evidence-based CV therapies in HIV populations

Lung

Epidemiology

Scientific Gaps

Approaches to Gaps

  • Incidence/prevalence of HIV-related chronic lung disease (COPD, PH)
  • Interplay of HIV, inflammation, anti-retroviral therapy, co-infections, and traditional risk factors on development of chronic lung disease
  • Enrich existing HIV cohorts with detailed information on pulmonary function/imaging, clinical data, and other lung evaluations
  • Enrich ongoing lung cohorts with HIV patients to provide detailed pulmonary data

Pathophysiology

Scientific Gaps

Approaches to Gaps

  • Mechanisms of the interplay of HIV, inflammation, anti-retroviral therapy, co-infections, and traditional risk factors in development and progression of chronic lung disease
  • Synergy of pathophysiological mechanisms with smoking
  • Conduct hypothesis-based studies investigating pathogenesis of HIV-related chronic lung disease Prevention and Treatment

Scientific Gaps

Approaches to Gaps

  • Strategies to optimize therapy/prevention of HIV-related chronic lung disease
  • Strategies to optimize strategies for smoking cessation in the HIV population
  • Leverage large medical databases to evaluate medical practice patterns and outcomes for chronic lung disease in HIV patients
  • Conduct studies evaluating smoking cessation interventions and efficacy of existing therapies for chronic lung disease in HIV patients
  • Conduct studies on HIV-related PH and enroll HIV patients into ongoing PH trials

Blood

Epidemiology

Scientific Gaps

Approaches to Gaps

  • Understand incidence/prevalence of anemia in patients with HIV
  • Understand incidence/prevalence of venous/arterial thrombosis
  • Utilize existing HIV cohorts to assess the prevalence of cytopenia and associations with other markers of non-infectious HIV complications
  • Utilize existing HIV cohorts to assess the prevalence of thrombotic complications and their determinants

Pathophysiology

Scientific Gaps

Approaches to Gaps

  • Mechanisms of HIV-related cytopenia
  • Rates of infection of subsets of hematopoietic stem cells/progenitor cells and surrounding cells in the niche
  • Mechanisms ofHIV resistance of hematopoietic stem cells/progenitor cells
  • Role of xenograft experiments in defining functionally important resistant cells
  • Mechanisms of HIV-related coagulation abnormalities and thrombosis events
  • Investigate primary stem cell defects, changes in stem cells or the microenvironment, role of inflammation
  • Investigate autologous and allogeneic stem cell transplant in appropriate animal models
  • Identify how the components of stem cell transplantation (conditioning regimen, type of cells transplanted, role of graft vs. host disease) interact to eradicate HIV
  • Conduct cell processing/expansion research to obtain sufficient numbers of HIV-resistant hematopoietic stem/progenitor cells
  • Assess how HIV affects coagulation pathways and biomarkers of thrombosis

Prevention and Treatment

Scientific Gaps

Approaches to Gaps

  • Novel therapies for HIV-related cytopenia
  • Role of stem cells as potential cures for HIV
  • Conduct trials addressing HIV-related cytopenias with multi-disciplinary investigative teams
  • Conduct translational research and early phase trials evaluating different stem cell regimens and the use of modified/expanded HIV-resistant cell therapies

Research Strategy Themes

WG participants strongly endorsed greater communication, collaboration, and teamwork among investigators and NIH Institutes to effectively address HIV-related heart, lung, and blood disease and to successfully develop the NHLBI AIDS Program. Other major recommendations were to leverage current research infrastructure, support training of new investigators, and develop metrics to measure results.

  • Communication
    • Communicate with professional societies focused on HIV, and heart, lung, and blood disease and cellular/gene therapies, to disseminate information about this emerging field, as well as the NHLBI AIDS Program
    • Create opportunities for inter-disciplinary communication by leveraging current HIV research programs and inviting sub-specialists to join in group discussions; similarly, support participation of HIV researchers in ongoing sub-specialty study discussions.
    • Develop a central location for information about the NHLBI AIDS Program and opportunities for research and collaboration
  • Collaboration and Teamwork
    • Collaborate with other NIH Institutes and other government agencies to understand how best to leverage existing programs
    • Collaborate with NHLBI program staff and leadership to understand how best to increase enrollment of HIV patients in ongoing heart, lung, and blood studies
    • Collaborate early with other NIH Institutes when developing new programs and initiatives focused on HIV-related heart, lung, and blood disease
    • Promote inter-disciplinary collaboration and teamwork by encouraging multiple principal investigators from different specialties on future initiatives; include inter-disciplinary collaboration and teamwork as a criteria for review
    • Develop initiatives that require collaborative teams, such as principal investigators from different disciplines
  • Leveraging Resources
    • Utilize existing HIV cohorts and studies and enrich with heart, lung, and blood-focused clinical and mechanistic endpoints; similarly, utilize existing heart, lung, and blood studies and increase enrollment of HIV patients whenever possible
    • Utilize infrastructure of HIV clinical trials networks to develop new HIV-related heart, lung, and blood-focused trials
    • Whenever possible, include and identify patients with HIV in ongoing heart, lung, and blood clinical trials; consider ancillary studies of ongoing trials focused on HIV patients
  • Training
    • Develop multi-disciplinary training awards that encourage mentorship and collaboration among HIV, heart, lung, and blood scientific communities
    • Cross-disciplinary training programs that allow both clinical and basic investigators to learn fundamentals of each scientific approach
  • Metrics
    • Develop specific benchmarks to measure the impact of new interventions. These may include the number of initiatives, applications, publications, and presentations at professional societies
    • Regular portfolio analysis to identify if scientific gaps are being addressed
    • Follow up WG to assess progress in research community

Publication Plans

A report is planned for publication in a peer-reviewed journal.

NHLBI AIDS WG Team

NHLBI Office of the Director

Susan Shurin, MD, Deputy Director, NHLBI

NHLBI AIDS Team

Monica Shah, MD, NHLBI AIDS Coordinator
Nakela Cook, MD, AIDS CV Team Leader
Hannah Peavy, MD, AIDS Lung Team Leader
Sandra Colombini-Hatch, PhD, AIDS Lung Team Leader
Simone Glynn, MD, AIDS Blood Team Leader
Shimian Zou, PhD, AIDS Blood Team Leader
Anthony Creazzo, PhD, Review
Myron Waclawiw, PhD, Statistics
Ryan Lombardi, Grants Management
Camille Jackson, Research Analyst

Program Chairs

Judith Currier, MD, University of California Los Angeles
Paul Ridker, MD, Brigham and Women's Hospital

Facilitators

Joseph Bocchino, EdD, The George Washington University
Shawneequa Callier, MA, JD, The George Washington University
Samar Nasser, PhD, MPH, PA-C, The George Washington University

Heart Group

Moderators
Judith Currier, MD, University of California Los Angeles
Paul Ridker, MD, Brigham and Women's Hospital
Priscilla Hsue, MD, University of California San Francisco

Participants
Deepak Bhatt, MD, MPH, Veterans Affairs Boston Healthcare
Gerald Bloomfield, MD, MPH, Duke University
Javed Butler, MD, MPH, Emory University
Steven Grinspoon, MD, Massachusetts General Hospital
Carl Grunfeld, MD, PhD, University of California San Francisco
James Neaton, PhD, University of Minnesota
Ivona Pandrea, MD, PhD, University of Pittsburgh
Eric Peterson, MD, MPH, Duke University
Jorge Plutzky, MD, Brigham and Women's Hospital
Wendy Post, MD, MS, Johns Hopkins University
Leslee Shaw, PhD, Emory University
James Stein, MD, University of Wisconsin
Rebecca Scherzer, PhD, University of California San Francisco

Lung Group

Moderators
Ronald Crystal, MD, Weill Cornell Medical College
Allison Morris, MD, MS, University of Pittsburgh

Participants
Ron Collman, MD, University of Pennsylvania
M. Brad Drummond, MD, MHS, Johns Hopkins University
Marshall Glesby, MD, PhD, Weill Cornell Medical College
Fred Gordin, MD, The George Washington University
Steven Kawut, MD, MS, University of Pennsylvania
Gregory Kirk, MD, PhD, MPH, Johns Hopkins University
Ken Kunisaki, MD, University of Minnesota
Myung Park, MD, University of Maryland
Bruce Thompson, PhD, Clinical Trials & Surveys Corporation

Blood Group

Moderators
Nancy Berliner, MD, Brigham and Women's Hospital
Daniel Kurtitzkes, MD, Brigham and Women's Hospital

Participants
Charles Abrams, MD, University of Pennsylvania
Richard Ambinder, MD, Johns Hopkins University
Michael Busch, MD, PhD, University of California San Francisco
Steven Deeks, MD, University of California San Francisco
Michelle Floris-Moore, MD, University of North Carolina Chapel Hill
Hans-Peter Kiem, MD, Fred Hutchinson Cancer Research Center
Scott Kitchen, PhD, University of California Los Angeles
Michael Lederman, MD, Case Western Reserve University
Nina Lin, MD, Massachusetts General Hospital
Mohandas Narla, DSc, New York Blood Center
Satish Pillai, MD, University of California San Francisco
Margaret Ragni, MD, MPH, University of Pittsburgh
Heather Ribaudo, PhD, Harvard School of Public Health
David Scadden, MD, Massachusetts General Hospital

Last Updated: November 2012

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