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HIV-associated Comorbidites, Co-infections, & Complications Workshop

September 19 - 20, 2019
Natcher Conference Center,
NIH Campus in Bethesda, MD

Description

People with HIV can now have nearly normal lifespans because of significant progress in HIV treatment, but the quality of their lives may be severely impacted by HIV-related comorbidities, co-infections, and complications. The overlapping etiologies and consequences of HIV-associated diseases need to be better understood on a holistic level.

The National Institutes of Health (NIH) Office of AIDS Research (OAR) funds research on HIV-associated comorbidities, co-infections, and complications through multiple Institutes and Centers (ICs), with a focus on diseases that fall within each IC’s mission and HIV/AIDS related funding priorities. This workshop fostered discussion among experts from different fields and disciplines who shared their perspectives and explored interrelationships among multiple comorbidities, in an effort to refine research priorities that aim to improve the health and well-being of people with HIV.

Recap

Executive Summary

The face of the HIV pandemic has changed dramatically since the 1980s. With potent antiretroviral therapy (ART) and simplified regimens, progression of HIV infection to acquired immunodeficiency syndrome (AIDS) may be significantly delayed or avoided, and people living with HIV are achieving near-normal lifespans. However, many are suffering from HIV-associated comorbidities, co-infections, and complications (HIV-associated CCCs), often against a background of multiple complicating factors such as stigma, isolation, and socio-economic challenges. 

To gain a better understanding of HIV-associated CCCs, and to foster cross-disciplinary collaborations in future research, 21 Institutes, Centers and Offices (ICOs) at the National Institutes of Health (NIH) jointly convened a workshop on September 19-20, 2019. The ICOs invited 96 experts and community representatives to prepare for the workshop by forming five working groups (WGs) and an international panel. More than 40 representatives from the 21 sponsoring NIH ICOs also joined one or more of the five WGs on the following topics: epidemiology and population science, pathogenesis and basic science, clinical research, implementation science, and syndemics (for instance, disease interactions and social, cultural, environmental, political, and economical factors that influence or exacerbate diseases or conditions). The five WGs assembled in November 2018 and worked via multiple teleconferences to identify research gaps and opportunities for further discussion at the September 2019 workshop.

More than 400 participants attended the two-day workshop onsite and remotely. During the meeting, the five WGs and the international panel posed key questions to stimulate discussion on research priorities in their fields. Attendees also heard the unique perspective of a member of the HIV community who has long lived, and is now aging, with HIV. Such broad representation ensured that all relevant views were reflected; it also provided opportunities for investigators in different disciplines and fields to communicate with each other and exchange ideas and perspectives.

From the discussion, it became clear that it is unlikely one discipline alone can advance the HIV research field, as multiple organ systems are impacted by chronic HIV infection, comorbidities (HIV-associated and not), and drug toxicities and interactions related to treatment of both HIV infection and the comorbidities. Because of this complexity, many scientific questions remain unanswered.  A major challenge of such research is its high cost, which is why a more coordinated, cross-disciplinary research approach is needed. These more cost-effective efforts could focus on investigating mechanisms of pathogenesis and testing prevention or clinical management interventions for multiple HIV-associated CCCs. This report details the priorities and opportunities identified during the workshop.

The workshop discussion encompassed several main themes:

  • HIV-associated CCCs affect multiple organ systems and result in a broad range of health consequences and outcomes affecting morbidity and mortality. They negatively impact the quality of life and healthspan of people living with HIV, even in the presence of ART and in spite of improved lifespan. 
  • Underlying pathogenic mechanisms may be shared among HIV-associated CCCs that involve multiple systems and manifest as various concurrent conditions in people living with HIV. These may be fundamentally different from those that result in the same “diagnosis” in people living without HIV. 
  • The appropriate phenotypes, indicators and indices/biomarkers for research on HIV-associated CCCs will likely prove to be distinct among people living with HIV.
  • Several overlapping etiologies and mechanisms contribute to the development of HIV-associated CCCs. These include factors and shared pathways that drive chronic immune activation and dysfunction in treated HIV infection and mechanisms that drive accentuated aging.
  • New research methods and technologies, including appropriate animal models, are needed to study HIV-associated CCCs across the lifespan.
  • Research related to the prevention and management of HIV-associated CCCs is complicated because intervention strategies must consider drug-drug interactions with ART and therefore may need to be tailored to people living with HIV. Since people living with HIV may also have multiple comorbidities, research may also need to target these complexities. 
  • Multiple factors likely contribute to health in aging people living with HIV, including the direct impacts of HIV on multiple organ systems, toxicity of ART, polypharmacy, social isolation, stigma and likely many other still poorly defined risk factors. Notably, most of these factors are known to affect aging in the general population, but are over represented or more pronounced in people living with HIV.
  • The impacts of social, cultural, economic, political and other factors on the susceptibility to and treatment of HIV infection and other co-occuring conditions are not fully understood. Questions related to how these factors differ within and among at-risk populations, as well as the best ways to study them, remain largely unanswered.
  • Syndemics research could help characterize various comorbid diseases/disorders and their synergistic effects in the context of socio-economic, political, and ecological factors in people living with HIV. As such, syndemics research can help us gain a deeper understanding of the interplay of these factors and their role in promoting disease clustering at the population level, and the impact they have on disease pathologies at the individual level. Findings of such research will encourage more holistic approaches in the clinical management of people living with HIV.
  • Because implementation science is a relatively new area of research, coordinated support is needed not only to develop implementation research studies, but also to train scientists in implementation science, which could include leveraging existing training opportunities and resources. Implementation science strategies are needed to address barriers that impede the scale-up and application of scientifically proven interventions in community and clinical settings. These interventions must focus on the prevention, control, and treatment of HIV-associated CCCs in people living with HIV. 

Opportunities identified include:

  • A coordinated NIH-wide research strategy. This would be optimal for addressing HIV-associated CCCs, since they involve multiple organ systems and concurrent conditions. A coordinated strategy would complement efforts targeting specific research priorities within the mission of each ICO. 
  • Multidisciplinary strategies. These would address the common research themes, which require fostering a non-siloed, collaborative approach and encouraging further investigation across multiple areas: basic mechanisms of pathogenesis that contribute to the development of HIV-associated comorbidities, the safety and effectiveness of interventions to control inflammation and mitigate chronic immune activation in people living with HIV, syndemics, and implementation science.
  • Innovative models. These would more effectively support future research on HIV-associated CCCs. Research support models should allow researchers to address the complexities of multiple comorbidities and influential factors, including socio-economic factors, and encourage collaboration. For example, multi-omics approaches and large cohorts require collaboration across ICOs. Workshop participants encouraged NIH-wide discussions on how to facilitate and fund such collaborative research.

Now more than ever, there is an urgent need for a coordinated research effort to address HIV-associated CCCs and the impact of aging. Increasing numbers of people living with HIV are expected to enter into care as a result of the President’s initiative to end the HIV epidemic in the United States in 10 years. Called “Ending the HIV Epidemic: A Plan for America,” the initiative was announced in 2019. The research priorities identified during the workshop and outlined in this document may prove vital in any optimized system of HIV care or treatment cascade designed to prevent and manage HIV-associated CCCs and ultimately improve the quality of life of people living with HIV. 

For the full recap, please see below:

Agenda

9:00 AM - 9:05 AM
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Welcome and Acknowledgement [slides]

Dr. Shimian Zou, Ms. Natalie Tomitch, and Dr. Leia Novak on behalf of the NIH Planning Committee

9:05 AM - 9:20 AM
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Opening Remarks

Dr. Keith Hoots and Dr. Timothy Holtz

9:20 AM - 10:30 AM
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Session 1: Introduction

Moderators: Dr. Steven Deeks and Dr. Savita Pahwa

Purpose of the Workshop (10 mins): Dr. Steven Deeks and Dr. Savita Pahwa [slides]

HIV in 2019 – Successes of ART and Challenges of Comorbidities [slides] (30 mins): Dr. Anthony Fauci

Current Burden of HIV-associated Comorbidities, Coinfections and Complications [slides] (30 mins): Dr. Keri Althoff

10:30 AM - 10:50 AM
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Break

10:50 AM - 11:50 AM
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Session 2: Epidemiologic research

Overview (10 mins)
Moderator: Dr. Amy Justice

What patient salient, and/or patient reported, outcomes are most useful to gauge health related quality of life and prognoses? [slides] (5 mins): Dr. Amy Justice
Discussion (15 mins)

Neurobehavioral Complications of HIV in the Modern Treatment Era: Challenges and Priorities for the Future [slides] (5 mins): Dr. Igor Grant
Discussion (15 mins)

How does HIV, risk behaviors, and ART influence aging syndromes, particularly falls, multimorbiditiy, polypharmacy, and frailty? [slides] (5 mins): Dr. Vincent Lo Re
Discussion (15 mins)

11:50 AM - 12:45 PM
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Lunch

12:45 PM - 1:45 PM
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Session 3: Pathogenesis/Basic Science research

Moderator: Dr. Dana Gabuzda

Immunopathogenesis overview [slides] (10 mins): Dr. Peter Hunt
Discussion (10 mins)

Microbiome/Virome overview [slides] (10 mins): Dr. Ronald Collman
Discussion (10 mins)

Aging and Senescence overview [slides] (10 mins): Dr. Beth Jamieson
Discussion (10 mins)

1:45 PM - 2:45 PM
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Session 4: Clinical research

Moderators: Dr. Todd Brown and Dr. Ann Kurth

Overview (5 mins): Dr. Todd Brown

Prevention as Treatment: Clinical and Translational Studies to Prevent Comorbidities (5 mins): Dr. Allison Agwu
Discussion (10 mins)

Comorbidity Management in HIV: Should it be the same as the general population or tailored? (5 mins): Dr. Kristina Crothers
Discussion (10 mins)

Patient-Reported Outcomes and Biomarkers (5 mins): Dr. Thomas Uldrick
Discussion (10 mins)

Sum-up (5 mins): Dr. Ann Kurth

2:45 PM - 3:00 PM
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Break

3:00 PM - 4:00 PM
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Session 5: Implementation Science research [slides]

Moderators: Dr. Stefan Baral and Dr. Michael Mugavero

Introduction to Implementation Science (IS) Research (5 mins): Dr. Denis Nash
Discussion (10 mins)

Synthesizing Priority IS HIV Co-morbidity Research Questions (5 mins): Dr. JD Smith
Discussion (10 mins)

Novel Observational and Experimental IS Research Designs (5 mins): Dr. Elvin Geng
Discussion (10 mins)

Training Opportunities and Resources to Expand the IS Research Workforce (5 mins): Dr. Mari-Lynn Drainoni
Discussion (10 mins)

4:00 PM - 5:00 PM
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Session 6: Syndemics

Moderators: Dr. Ada Adimora and Dr. Steven Safren

Introduction/Overview (5 mins): Dr. Ada Adimora

HIV-NCD Syndemic Production [slides] (10 mins): Dr. Emily Mendenhall

Syndemic Methods (10 mins): Dr. Alex Tsai

HIV-Infectious Disease Syndemics [slides] (10 mins): Dr. Kenneth Mayer

Discussion (25 mins): Dr. Steven Safren

8:45 AM - 9:00 AM
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Recap of Day 1

Dr. Steven Deeks  [slides]

9:00 AM - 9:30 AM
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Session 7: Clinical trials targeting aging to extend healthy lifespan: the TAME trial: Dr. Jamie Justice [slides]

9:30 AM - 10:30 AM
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Session 8: Panel on international research [slides]

Moderators: Dr. Roger Detels and Dr. Eugene Mutimura

10:30 AM - 10:45 AM
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Break

10:45 AM - 12:15 PM
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Session 9: Breakout Discussion by Working Groups

10:45 AM - 12:15 PM
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Epidemiologic and Population Research Breakout Session
Balcony B

Dr. Amy Justice and Dr. Ned Sacktor

This breakout session will examine how observational research in clinical and population settings can address problems of aging with HIV infection (e.g. falls, frailty, mental health conditions, and neurocognitive function). The session will focus on determining what are the most important questions and how best to address them with observational data.

10:45 AM - 12:15 PM
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Pathogenesis/Basic Science Research Breakout Session
Balcony A

Dr. Dana Gabuzda and Dr. Peter Hunt

This breakout session will examine the factors that drive chronic inflammation and immune dysregulation in treated HIV infection, changes in the microbiome and microbiome-host interactions, and how these events influence multiple end-organ diseases. The group will also discuss the biological mechanisms that may drive accentuated aging and impact age-related comorbidities in treated HIV infection.

10:45 AM - 12:15 PM
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Clinical Research Breakout Session
Main Auditorium

Dr. Ann Kurth and Dr. Todd Brown

This breakout session will focus on optimizing clinical research across the lifespan to address screening, prevention, and management of HIV co-morbidities. The group will discuss clinical trial designs that prioritize participant engagement and perspective, surrogate markers, and disparities.

10:45 AM - 12:15 PM
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Implementation Science Research Breakout Session
Balcony C

Dr. Stefan Baral and Dr. Michael Mugavero

This breakout session will focus on prioritizing training and research into optimal strategies for implementing clinical services and public health programs focused on addressing HIV-related comorbidities.

10:45 AM - 12:15 PM
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Syndemics Research Breakout Session
Room A/B

Dr. Emily Mendenhall and Dr. Ken Mayer

This breakout session will examine different aspects of syndemics such as how social, cultural, environmental, political, and economic factors produce vulnerability for HIV and co-conditions, how these factors differ within and between populations, how they may simultaneously affect HIV, non-communicable as well as communicable (co-infection) disease risk, and how syndemics mediated by social/structural factors affects behavioral outcomes. We will also discuss the methodology needed to address syndemic interactions.

12:15 PM - 1:00 PM
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Lunch

1:00 PM - 1:50 PM
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Session 10: Report from Working Group Breakouts

Moderators: Dr. Steven Deeks and Dr. Savita Pahwa

Epidemiologic research [slides]: Dr. Amy Justice

Pathogenesis/Basic Science research [slides]: Dr. Dana Gabuzda and Dr. Peter Hunt

Clinical research [slides]: Dr. Ann Kurth and Dr. Todd Brown

Implementation Science research [slides]: Dr. Stefan Baral and Dr. Michael Mugavero

Syndemics [slides]: Dr. Emily Mendenhall and Dr. Ken Mayer

1:50 PM - 2:00 PM
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Session 11: HIV Community Perspective: Aging with HIV in the US: Jules Levin [slides]

2:00 PM - 2:50 PM
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Session 12: Panel Discussion for Consensus Building

Moderators: Dr. Steven Deeks and Dr. Savita Pahwa

2:50 PM - 3:00 PM
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Closing Remarks

Dr. Steven Deeks and Dr. Savita Pahwa