Notice of Special Interest (NOSI): Leveraging existing HIV observational cohorts to study HIV-associated HLBS disorders

Notice Number: NOT-HL-19-705

Key Dates
Release Date: June 3, 2019

Related Announcements
PA-19-056: NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

Issued by
National Heart, Lung, and Blood Institute (NHLBI)

Purpose

The purpose of this Notice is to inform potential applicants to the National Heart, Lung, and Blood Institute (NHLBI) of an area of special interest in supporting analysis of existing or newly-collected data and biological specimens within existing HIV-related cohort studies.

Background

The HIV/AIDS pandemic has been one of the most important global health challenges in modern history. Current antiretrovial therapy (ART) has evolved to effectively control HIV replication, prevent AIDS, and contribute to the prolonged life of infected individuals. ART does not eliminate the virus from the body, but in many cases, it can suppress the virus to undetectable levels, significantly reducing the risk of viral transmission. Even with successful viral suppression while on ART, low levels of viral replication persist in HIV reservoirs residing in various tissues and can contribute to sustained systemic immune activation and inflammation in people living with HIV (PLWH). Furthermore, use of ART itself may promote or exacerbate immune dysfunction and thereby negatively impact heart, lung, blood, and sleep (HLBS) diseases, particularly in combination with inflammation and immune activation induced by residual HIV reservoirs.

The impact of long-term ART use on HLBS diseases is an understudied but significantly important research area. This NOSI encourages applications that propose research that will advance our understanding of the effect(s) of long-term ART use on HIV-related HLBS diseases.

Research Objectives

NHLBI is interested in receiving applications that incorporate interdisciplinary research collaborations, particularly between established and junior investigators, and propose to leverage existing HIV observational cohorts to study HIV-associated HLBS disorders.

Examples of HIV-cohorts that could be utilized, include, but are in no way limited to, the MACS/WIHS-Combined Cohort Study, cohorts affiliated with the Pediatric HIV/AIDS Cohort Study (PHACS), the CFAR Network of Integrated Clinical Systems (CNICS), the International epidemiology Databases to Evaluate AIDS (IeDEA), the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), and other U.S. and international HIV-cohort studies. Creation of new HIV cohorts is not supported.

Specific areas of research interest include, but are not limited to:

  • Understanding the combined effect of ART drugs and drugs to control HLBS comorbidities in the aging population
  • Studies to delineate viral, host, or ART treatment components as determinants that induce accelerated aging and the earlier onset of HLBS comorbidities
  • Determining the incidence and prevalence of, as well as viral, host, or ART treatment-related mechanisms contributing to sleep disorders in PLWH
  • Investigation and comparison of HLBS disease progression (e.g., coronary artery disease, lung function decline) in adolescents vs. adults living with HIV
  • Studies focused on the evaluation of risks for developing non-infectious HLBS comorbidities and complications in perinatally HIV-infected individuals (now adolescent and adults) who have received long-term ART
  • Studies aimed to identify biomarkers to better predict progression of lung disease (T-cells, HIV-specific immune responses, macrophage activation), and to better understand the mechanism of HIV-associated persistent inflammation in the lung
  • Host mechanisms of immune defense that might be subverted under ART, rendering the host more susceptible to pulmonary co-infections, including Tuberculosis
  • Understanding the role of viral proteins in HIV-related pulmonary hypertension in PLWH on ART
  • Determining the impact of HIV on hematopoiesis, particularly megakaryocytic development and function, and the implications for bleeding and thrombosis
  • Studies to identify the role of inflammation, immune dysregulation, or endothelial, platelet, and coagulation activation in the etiology of vascular events in HIV infection
  • Evaluation of the effects of HIV infection and ART on platelet function. Also, determine how ART, combined with tobacco smoke, further potentiates platelet dysregulation, chronic inflammation, and the development of cardiovascular disease.
  • Evaluation of the effects of heart failure on HIV pathogenesis and disease progression
  • Development of novel biomarkers, imaging, and therapeutics to more accurately diagnose and treat HIV-related heart failure with preserved ejection fraction
  • Studies to determine the interplay and role of environmental, social, and lifestyle factors involved in promoting HIV-associated HLBS comorbidities among PLWH
  • Studies to identify novel approaches and technologies to address these research questions

Application and Submission Information:

This Notice applies to due dates on or after September 7, 2019 and expires on January 8, 2022 .

Applications in response to this Notice must be submitted through PA-19-056, NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). All instructions for PA-19-056 must be followed.Investigators planning to submit an application in response to this NOSI are strongly encouraged to contact and discuss their proposed research/aims with the NHLBI program officer listed on this NOSI well in advance of the grant receipt date.

For funding consideration, applicants must include NOT-HL-19-705 in the Agency Routing Identifier field (Box 4.b) of the SF 424 (R&R) Form. Applications without this information in Box 4.b will not be considered for this initiative.

Inquiries

Please direct all inquiries to:

Sean Altekruse D.V.M., Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-1290
Email: altekrusesf@nhlbi.nih.gov