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

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: