Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute on Aging (NIA) National Cancer Institute (NCI) National Heart, Lung, and Blood Institute (NHLBI) National Institute on Alcohol Abuse and Alcoholism (NIAAA) National Institute of Allergy and Infectious Diseases (NIAID) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) National Institute on Drug Abuse (NIDA) National Institute of Mental Health (NIMH) National Institute of Neurological Disorders and Stroke (NINDS)
Funding Opportunity Title	Multidisciplinary Studies of HIV/AIDS and Aging (R21)
Activity Code	R21 Exploratory/Developmental Research Grant Award
Announcement Type	New
Related Notices	June 18, 2015 - This PA has been reissued as PAR-15-282. June 3, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same. November 15, 2013 - See Notice NOT-OD-14-022. Application Due Date Adjustments Based On Grants.gov Scheduled Downtime December 6-9, 2013. May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013. July 18, 2012 - See Notice NOT-AA-12-005. Notice of NIAAA Participation. July 5, 2012 - See Notice NOT-AG-12-011. The purpose of this Notice is to announce a publication related to recently released FOA's
Funding Opportunity Announcement (FOA) Number	PAR-12-174
Companion Funding Opportunity	PAR-12-175, R01 Research Project Grant PAR-12-176, R03 Small Grant
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.866, 93.393, 93.394, 93.395, 93.396, 93.399, 93.856, 93.846, 93.865, 93.279, 93.242, 93.853, 93.837, 93.838, 93.839, 93.233, 93.273
Funding Opportunity Purpose	This FOA invites applications proposing to study HIV infection, HIV-associated conditions, HIV treatment, and/or biobehavioral or social factors associated with HIV/AIDS in the context of aging and/or in older adults. Research approaches of interest include clinical translational, observational, and intervention studies in domestic and international settings.

Posted Date	April 24, 2012
Open Date (Earliest Submission Date)	July 7, 2012
Letter of Intent Due Date	Not Applicable.
Application Due Date(s)	August 7, 2012; December 7, 2012; April 9, 2013; August 7, 2013; (Extended to December 10, 2013 per NOT-OD-14-022) December 6, 2013; April 9, 2014; August 7, 2014; December 9, 2014; April 7, 2015, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	Standard dates apply
Advisory Council Review	Standard dates apply
Earliest Start Date(s)	Standard dates apply
Expiration Date	April 8, 2015
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

BACKGROUND

The number of older individuals living with HIV/AIDS has risen dramatically over the last decade. From 2001-2008, the proportion of Americans living with HIV who were aged 50 years or older rose from 17% to nearly 31% (1). By 2015, more than half of all HIV-infected Americans are projected to be over the age of 50 (2).

The rise in HIV prevalence among older Americans is attributed primarily to two factors. First, effective treatment with highly active antiretroviral therapy (HAART) has led to a marked increase in survival among individuals who were infected in their younger years and are now living into older age. Second, new infections have increased among older adults: in 2001, Americans aged 50 and older accounted for 13% of new HIV diagnoses, and in 2008, the rate was over 16% (1).

While HAART has led to a marked reduction in the incidence of AIDS-defining illnesses, a variety of HIV-Associated Non-AIDS (HANA) conditions are becoming increasingly commonplace in individuals with long-standing HIV infection. These conditions include cardiovascular disease, lung disease, infection-related and non-infection-related cancers, HIV-Associated Neurocognitive Disorders (HAND), neuropsychiatric disorders, osteopenia/osteoporosis, liver cirrhosis, and renal disease. It is unclear whether HIV infection and/or its treatment lead directly to these conditions, which might suggest an "acceleration of aging," or whether HIV infection and/or treatment confer additive risk of developing HANA conditions in aging individuals. Nevertheless, it is clear that individuals living with prolonged HIV infection exhibit many of the clinical characteristics commonly observed in aging, such as multiple co-morbidities, polypharmacy, physical and cognitive impairment, functional decline, alterations in body composition, and increased vulnerability to stressors. Moreover, the clinical picture of HIV in older adults may be complicated by many other risk factors, including infections with oncogenic viruses (e.g., Human papillomavirus [HPV], Kaposi-sarcoma Associated Herpesvirus [KSHV/HHV-8], Epstein-Barr virus [EBV], hepatitis B Virus [HBV], and hepatitis C virus [HCV]), obesity, and licit and illicit substance abuse including nicotine, alcohol, marijuana, and prescription drugs. As such, improved management of older individuals with HIV will require a much deeper understanding of the interface between aging, HIV, associated co-morbid conditions, and concurrent treatment. In addition, research is needed to address the unique psychosocial challenges faced by this growing population.

Recent activities within and outside the NIH have highlighted the importance of enhanced research on HIV in aging populations. In October, 2007, the Association of Specialty Professors, along with NIA, NIAID, the Infectious Diseases Society of America, and the HIV Medical Association, organized a workshop on HIV and aging, whose proceedings were published in Effros et al. Clinical Infectious Diseases 2008; 47:542-553). In 2011, the NIH Office of AIDS Research (OAR) established the Working Group on HIV and Aging, a panel of academic and community experts charged with identifying current and high priority research opportunities in HIV and aging. A report from this Working Group is currently in press in the Journal of Acquired Immune Deficiency Syndromes (JAIDS). This FOA builds on the recommendations that have emerged from these efforts.

SCOPE

The goal of this announcement is to invite research grant applications studying HIV infection, HIV-associated conditions, HIV treatment, and/or biobehavioral or social factors associated with HIV/AIDS in the context of aging and/or in older adults. Research approaches of interest include clinical translational, observational, and intervention studies in domestic and international settings. General topic areas appropriate for this FOA include, but are not limited to the following:

Cellular and molecular mechanisms of HIV in aging

It is now recognized that innate and adaptive immune cells play an important physiological role in eliminating senescent cells and maintaining normal tissue architecture across the lifespan. Many, though not all, changes typical of the aging immune system are also observed in individuals with HIV. Some studies have characterized changes in the adaptive immune system with HIV infection, but knowledge gaps still exist in our understanding of long-term changes with treated infection or in the setting of chronic substance use and abuse. In addition, less is understood about changes in the innate immune system associated with HIV over time. Moreover, most studies evaluate immune function through assays of peripheral blood, which contains only a fraction of the body's immune cells. Investigators are encouraged to expand studies to include other tissues including brain, bone marrow, gut mucosa, skin, lymph nodes, and other lymphoid tissues. Studies should also relate cellular, molecular, or genetic measures to clinical outcomes. Finally, insights into immune system pathophysiology gleaned from other immune-mediated diseases, such as rheumatoid arthritis, may provide useful research directions for applications responsive to this FOA. Examples of relevant topics at the intersection of HIV, aging, and the immune system may include, but are not limited to:

• Understanding alterations in innate and adaptive immunity with long-standing infection, including changes in regulatory T-cell frequency and function
• Understanding the role of cytomegalovirus or other chronic viral infections in immune system changes associated with HIV infection
• Understanding how HIV infection alters the human microbiome and the effect of such changes on chronic inflammatory and autoimmune diseases
• Elucidating the relationship of telomere biology to clinical parameters of HIV disease and associated co-morbidities such as cancer.
• Understanding the role of neuroendocrine factors in the development of HIV-associated immune system changes with age
• Understanding the relationship between chronic immune activation in HIV-infected individuals and the development of a chronic inflammatory state
• Gaining a better understanding of the effects of HIV-associated immune dysfunction on the immunosurveillance of senescent cells.
• Elucidating how aging and HIV impact the gut microenvironment and cancer pathology.
• Analyses of the role of chronic inflammation in HIV and the development of cancer.
• Examining the contribution of HIV-associated immunosenescence in the central nervous system (CNS) and its impact on the pathophysiology of neurocognitive dysfunction.

HANA Conditions / Co-morbidities

A variety of co-morbid diseases and conditions may arise in the setting of long-standing treated HIV infection. These include insulin resistance, dyslipidemia, cardiovascular disease, cancers (infection- and non-infection-related), renal impairment, metabolic bone disease, liver disease, neurological diseases, and neuropsychiatric disorders. All of these conditions may develop in aging individuals without HIV infection, but the additive effects of HIV infection and/or its treatment on development or progression of these conditions is not well understood. Investigators have proposed that such comorbidities not directly referable to HIV infection may be the consequence of chronic HIV infection, long-term ART toxicities, or a state of chronic inflammation, but further research is needed to disentangle whether these factors are causal, concurrent, or sequential to HIV infection.

Further studies are needed to refine our understanding of the complex relationships among HIV infection, HIV treatment, aging physiology, and other biological and psychosocial co-occurring conditions. Finally, a variety of prevention guidelines are available for HANA conditions, based largely on evidence from non-HIV populations. It is unclear whether adherence to such guidelines in multiply-morbid individuals with HIV results in improved health, increased survival, or cost-effective care comparable to those in age-matched populations without HIV. Studies on HANA conditions may include, but are not limited to:

• Identification of clinical or demographic sub-groups with differential susceptibility to development of specific HANA conditions or successful or adverse responses to treatment.
• Evaluation of adherence to, or variations from, guideline-driven prevention strategies for HANA conditions in aging HIV-infected individuals.
• Evaluation of strategies balancing potential toxicities of ART against prevention or treatment of conventional risk factors for HANA conditions.
• Lifespan studies to better understand temporal development of comorbidities, which may reveal antecedent, concurrent, and sequential relationships with HIV infection and thereby identify potentially causal targets for intervention.
• Elucidation of mechanisms through which aging processes contribute to development of HIV-related cancers and their precursors or to responses to treatment of HIV-related malignancies.
• Analysis of the interactions between age, CD4+ cell count, ART exposure, cancer incidence and outcomes.
• Assessment of the cancer prevention and early detection needs of aging HIV-infected patients.
• Understanding interactions between mental health issues (e.g., neuropsychiatric comorbidites), aging-related changes (e.g., declining physical and cognitive function), and their intersection with the development and progression of HIV disease and its related dementias.
• Research on the interaction between aging, HIV infection, and HAART therapy on the development of arterial vasculopathy (e.g., coronary artery disease and pulmonary hypertension)
• Research that examines the effect of known effective cardiovascular disease prevention strategies for the aging population such as diet, physical activity, and exercise on metabolic and lipid parameters in patients taking HAART therapy
• Research comparing mechanisms of sudden cardiac arrest and ventricular arrhythmias in patients with HIV (both on and off HAART therapy)
• Investigating the role of chronic inflammation in the pathogenesis of cardiovascular disease and lung disease

Biomarkers or clinical indices of HIV-associated pathology

Development and validation of biomarkers for development or progression of HIV/AIDS disease status or HANA conditions may produce useful surrogate measures of important clinical outcomes. Such biomarkers may be used to measure comorbid disease status and response to therapy, as well as point to potential underlying mechanisms that may be amenable to intervention; however, relationships between biomarkers and the outcomes they may be associated with may be impacted significantly by ART effects, co-infections, or other comorbidities. Pro-inflammatory cytokines, such as IL-6, and markers of declining renal function, such as cystatin C, have proven to be valid indicators in HIV-infected adults. Other biomarkers deserving further study, individually or as part of combined indices, include, but are not limited to:

• C-reactive protein (CRP) and other acute phase reactants
• D-dimer
• Soluble CD14
• Novel applications of traditional markers of HIV infection (CD4 count, viral load)
• Markers of T-cell activation (CD38, HLA-DR)
• Markers of T-cell senescence (CD28, CD57)
• Markers of B-cell activation (AID, IL10, soluble CD23 (sCD23), sCD27, sCD30),
• Red blood cell indices (hemoglobin, mean corpuscular volume, red cell distribution width)
• Markers of liver injury (e.g., FIB-4, AST:platelet ratio index [APRI])
• Markers of NeuroAIDS (e.g., MCP-1, neopterin, osteopontin, ApoE-epsilon4)
• Markers associated with neurodegenerative diseases (e.g., amyloid, Abeta42, ApoE, tau, phospho-tau)
• Markers associated with cardiac disease (e.g., Cardiac Troponin and B-Type Naturetic Peptide)

HIV-Associated Neurocognitive Disorders (HAND)

It is estimated that over 50% of HIV-infected individuals in the US have HAND, a significant cause of interference with activities of daily living and reduced quality of life. Age is a significant risk modifier for HAND, and there is a growing body of evidence indicating overlapping neuropathology between aging-associated neurodegenerative diseases and HAND. Although brain pathology differs between HAND and Alzheimer’s disease, brains from patients with HAND often show accumulation of abnormal protein such as amyloid-beta. A variety of biological or environmental factors, including genetic factors and chronic substance abuse, may contribute to neurodegenerative processes in aging HIV-positive individuals. Examples of studies on neurologic and neuropsychiatric complications in older HIV-infected individuals include, but are not limited to:

• Elucidating interactions among HIV infection, HIV treatment, and development or progression of cognitive decline or dementia in older adults.
• Understanding relationships among cerebrovascular factors associated with neurocognitive impairment, HIV infection, HAART effects, and aging-related co-morbid conditions such as diabetes, hypercholesterolemia, and stroke.
• Developing or expanding imaging tools to study HIV-aging interactions or HIV-related neurodegeneration.
• Understanding aspects of HIV infection that uniquely influence the aging nervous system and neurocognitive function.
• Elucidating pathways to deregulated gene/protein expression (e.g., amyloid-beta), mitochondrial dysfunction, autophagy, dendritic degeneration or dysregulated axonal transport associated with chronic HIV infection and long-term HAART.
• Elucidating common pathways shared by HAND and aging-related brain changes such as atrophy, neurotransmitter changes, alterations in blood-brain barrier integrity, and age-related neurodegenerative conditions (e.g., Alzheimer's disease and vascular dementia).
• Developing novel animal models to study effects of HIV and aging-related factors in neurodegenerative processes.
• Defining host genetic factors that alter susceptibility to HIV-related neurocognitive outcomes with aging.
• Investigating the role of neurotrophic factor-mediated repair mechanisms in older HIV-infected individuals.
• Examining the contribution of central nervous system inflammation and age-related immune changes to the pathogenesis of HAND.
• Characterizing CNS manifestations of HIV-associated immune reconstitution and inflammatory syndromes in aging HIV-infected adults.

In addition, several existing resources related to Alzheimer's Disease and dementia may be useful in pursuing studies related to HAND; for example, the Alzheimer's Disease Neurological Initiative (ADNI) can provide normative data for brain imaging and neurocognitive function in age-matched non-HIV-infected controls

Interventions

Evidence-based treatment for HIV in older individuals has been extrapolated largely from studies in younger individuals. While HIV-specific indicators of disease status may respond to such treatment, non-HIV-related indicators may respond less well or not at all. Innovative treatment approaches are also needed that target aging-related outcomes, such as maintaining physical and cognitive function, reducing polypharmacy, and managing multiple competing disease processes and their individual treatments. The risks and benefits of treating age-related comorbidities are particularly warranted. Preventative interventions, including primary prevention of HIV infections in older adults and prevention of development or progression of HANA conditions are also needed. Intervention studies may include, but are not limited to, the following:

• Development and evaluation of "geriatric" interventions, such as physical activity, dietary modification, fall assessment and prevention, maintenance/improvement of cognition, anti-inflammatory therapies, and medication adjustment.
• Development and evaluation of intervention strategies based on new or established risk indices that address modifiable factors (e.g., cardiovascular disease, respiratory disease, liver injury, renal impairment, diminished bone quality, bone marrow injury, neurological diseases, HCV infection, substance abuse).
• HIV prevention interventions in target populations.
• Studies to advance treatment-as-prevention in uninfected older adults at risk of HIV infection and determination of conditions under which treatment-as-prevention approaches are efficacious.
• Comparative effectiveness studies of pharmacological or combined pharmacological/non-pharmacological interventions, particularly incorporating patient and family preferences and evaluating cost effectiveness
• Interventions to promote subjective well-being and resilience, and to reduce symptom burden in older adults with HIV, including examination of the impact of individual differences (e.g. personality, sense of control, self-efficacy) on their effectiveness.
• Determination of the optimal treatment for HIV-associated cancers in the older population or other cancers not specifically related to HIV that develop in elderly HIV-infected individuals.
• Determination of the association between barriers to care and cancer outcomes in older HIV-infected individuals and development of appropriate interventions to improve cancer care.
• Integration of effective behavioral interventions with ongoing clinical trials into community clinics/setting and determining the most salient intervention components.
• Development of intervention programs targeting mechanisms of HIV-related disparities (e.g., social/sexual networks, access to and quality of health care, biological characteristics such as gender and genetic susceptibility) to improve provision of appropriate care and treatment in older HIV-infected individuals.
• Development of combination biomedical-behavioral interventions, advancing novel multilevel preventive interventions, and identifying core elements of multi-component evidence-based interventions.
• Operations research focusing on barriers, facilitating factors, and outcomes of scaling-up HIV prevention interventions with known efficacy for older adult populations.

Frailty / Vulnerability

Frailty has been defined as a multi-system syndrome of diminished physiologic reserve associated with increased vulnerability to stressors. Advancing age is a significant risk factor for developing frailty, though the mechanisms leading to it are complex, interrelated, and not well understood. Like individuals with other chronic diseases, those with long-standing HIV infection are at higher risk of developing frailty than newly-infected or non-infected age-matched controls. Studies are needed to improve our understanding of the relationship between HIV and development or progression of specific contributors to frailty in older HIV-infected individuals. Relevant studies may include, but are not limited to:

• Elucidation of the relationship between specific physical, cognitive, and/or psychosocial vulnerabilities and HIV infection.
• Identifying the relationship between age-related changes in body composition, including subcutaneous and visceral adipose depots, and HIV/AIDS progression and/or ART.
• Understanding the impact of HIV and its treatment on functional status, energy balance, or exercise tolerance.
• Elucidation of the role of mitochondrial toxicity due to HIV infection or treatment in age-related sarcopenia and muscle function.
• Analysis of the risk and level of frailty in HIV-infected individuals with cancer.
• Understanding the impact of HIV and co-morbidities in older cancer patients to determine predictors of disease progression and survival.

Social, behavioral, and mental health studies

The burgeoning population of older adults with HIV faces considerable challenges with regard to social engagement and interaction, adequacy of informal social supports and caregiving resources, and utilization of community-based services to meet growing needs. Individuals aging with HIV tend to have limited or inadequate social networks, particularly within traditional family structures. As a result, older individuals with HIV will need to rely more heavily on community-based services in the future; however, such resources may be ill-equipped to handle the complex psychosocial issues with which aging individuals with HIV frequently present. Moreover, older individuals infected with HIV earlier in life may be quite different from those who contracted HIV later in life. Understanding not only the variety of psychosocial co-morbidities in the aging HIV population, but also the positive psychology and related constructs of individuals who are aging successfully with HIV (e.g., mindfulness, hardiness, resilience, self-efficacy, spirituality) may lead to greater insights into management strategies for older adults living with HIV/AIDS. Examples of social and behavioral research studies include, but are not limited to:

• The impact of life-course factors, stress, stigma, social isolation, loneliness, substance abuse, depression, or economic or psychological resources on health outcomes (physical and cognitive), the availability and quality of social relationships and social networks, informal caregiving resources, and adherence to treatment regimens among older individuals with HIV/AIDS.
• The impact of stress, depression, anxiety, social isolation, elder abuse and neglect, poverty, low socioeconomic status, mental health co-morbidities, substance abuse, or other psychosocial factors on cognition in older adults with HIV.
• Mechanisms through which social, economic, and psychosocial stressors and protective factors favorably or adversely affect the course of HIV/AIDS.
• Development of demographic and prognostic models of HIV infection and the effect of ART on survival and health outcomes based on age/stage of diagnosis and treatment.
• Studies of health and well-being outcomes among older people in low-income countries who are either infected themselves or who are informal caregivers for people living with AIDS or for AIDS orphans.
• Projections of the health, long-term care, and social services needs of the older HIV/AIDS population.
• Analyses of the effects of financing, benefit design, and organization of services on the utilization of acute and long-term health care and patient outcomes.
• Understanding the impact of expanding life expectancies for HIV-infected individuals on HIV/AIDS resource allocation decisions and on public polices, such as Social Security Administration disability payment policy.
• Comparison of quality of life, treatment outcomes, and antiretroviral adherence in older versus younger HIV-infected individuals with cancer.
• Basic and applied behavioral and social science research to characterize the major phenotypes in aging populations (e.g., HIV-at risk, recently HIV-infected, long-term HIV-infected, premature aging HIV-infected, successful aging HIV-infected) and determine underlying mechanisms and most promising treatments for specific phenotypes.
• Studies to enhance the uptake of, or adherence to, efficacious interventions for older HIV-infected individuals.

General Considerations

In general this FOA encourages applications with the following characteristics:

• Clinical orientation. HIV in aging involves complex interactions among multiple physiologic systems and a variety of human-level factors such as functional status, quality of life, health behaviors, and psychosocial issues; therefore, studying individual factors in isolation may be counter-productive. This FOA encourages animal models and in vitro studies where appropriate; however, inclusion of such approaches should be integrated with human studies or demonstrate direct relevance to clinical features of HIV/AIDS.
• Focus on aging and/or the aged. Consistent with the Centers for Disease Control (CDC) definition of older HIV-infected individuals, applications should involve persons 50 years of age or older. Applicants are strongly encouraged to enroll individuals across the range of older ages, especially individuals at the upper end of the age range (i.e., 70 years or older). Comparisons between younger and older HIV-infected populations or comparisons between older HIV-infected individuals and their age-matched non-HIV-infected counterparts are appropriate approaches.
• Attention to geriatric outcomes. In addition to traditional outcomes of HIV/AIDS research are important (e.g., viral load, survival), studies should also include outcomes considered important in geriatric medicine and gerontology, such as physical function, cognitive status, quality of life measures, and social support.
• Use of existing resources where possible. A variety of NIH-funded resources are available to study HIV in aging, such as longitudinal studies of HIV-infected and/or their non-infected counterparts (observational or interventional), clinical networks, and research centers. Leveraging such resources through secondary analyses of available data, ancillary studies, or utilization of existing infrastructure are cost-effective approaches to testing hypotheses or generating relevant data for further studies
• Selection of appropriate controls. Aging individuals with HIV present with varied and complex clinical pictures. Biological and psychological co-morbidities, treatment regimens, lifestyle and behavioral factors, socioeconomic factors, and social support may all impact on disease development, coping, and progression. This complexity presents a significant challenge to identifying appropriate control populations in observational studies of aging individuals with HIV. Such studies should include adequate justification for selection of the proposed control group(s).
• Definition of phenotypes. Several biological or behavioral phenotypes of HIV in aging have been elucidated that may have markedly different disease courses, biological underpinnings, and treatment responses. Such phenotypes may be described by such characteristics as frailty/disability, accelerated aging, successful aging, or other descriptors. Investigators are encouraged to maximize the homogeneity of subgroups by defining specific phenotypes in analyses.

In addition to the general topic areas of interest above, additional areas of scientific interest specific to participating Institutes and Centers are detailed below.

National Cancer Institute (NCI)

NCI as a participating institute seeks to foster research studies to help understand how aging in the presence of chronic HIV infection affects the risk, spectrum and biology of cancer (AIDS-defining and non-AIDS-defining cancers). Recent data indicates an increase in the non-AIDS-defining cancers that is driven to a large extent by the growth and aging of the HIV/AIDS population. Aging is by itself a key factor promoting the development of many cancers, and there is a lack of data on the interplay between aging, HIV, long-term exposure to antiretroviral drugs, and other factors promoting cancer development in the aging population. In addition, there is little understanding of the interplay between host factors and immune perturbations that occur in aging and how these interactions affect cancers that are mostly seen in older people (e.g., Kaposi’s sarcoma and Merkel cell carcinoma).

National Heart, Lung, and Blood Institute (NHLBI)

NHLBI supports basic, clinical, and translational research on the prevention and treatment of heart, lung, blood, and sleep disorders. As the population of individuals living with HIV/AIDS ages, the interplay of the viral infection, antiretroviral therapies, and complicating chronic conditions becomes increasingly important. For this initiative, NHLBI is interested in clinical translational, observational, or interventional studies on topics such as, but not limited to:

• Understanding the changes in hematopoiesis that occur with HIV infection, including changes in the hematopoietic stem cells and the stem cell niche.
• Improving hematopoietic stem cell transplantation as a means to cure HIV infection.
• Development of pluripotent stem cells as a hematopoietic intervention and therapy for HIV.
• Understanding the impact of disordered sleep and sleep-disordered breathing on cardiovascular and pulmonary disease risks and exploring strategies to reduce these risks.
• Elucidating the impact of accelerated senescence on the pathogenesis of HIV-associated lung diseases including chronic obstructive pulmonary disease (COPD), HIV-associated pulmonary hypertension, and pulmonary fibrosis.
• Investigating the role of aging in the increased risk of developing bacterial pneumonias and subsequent loss of lung function and searching for novel therapeutic strategies to minimize lung injury.
• Elucidating the impact of chronic inflammation, abnormal endothelial function, altered coagulation, or other subclinical changes that can predispose HIV/AIDS-infected persons to premature or accelerated cardiovascular disease.
• Exploring strategies aimed at reversing or minimizing atherosclerosis and its clinical consequences by targeting underlying inflammation and endothelial dysfunction with medications or other treatment regimens.
• Interventions aimed at reducing cardiovascular disease by modifying or eliminating more traditional risk factors such as smoking, metabolic disturbances, hypertension, and coagulation abnormalities.
• Strategies employing novel biomarkers or other measures to detect subclinical cardiovascular disease and strategies to mitigate the manifestation of clinical disease.
• Research on the interaction between aging, HIV infection, and HAART therapy on the development of arterial vasculopathy (e.g., coronary artery disease and pulmonary hypertension).
• Research comparing mechanisms of sudden cardiac arrest and ventricular arrhythmias in patients with HIV (both on and off HAART therapy)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIAMS is interested in studies that investigate the effects of HIV infection and/or antiretroviral therapy on musculoskeletal and skin tissues and diseases. Proposed research should focus on chronic diseases and conditions in older adults and/or arising in the context of long term HIV infection and/or antiretroviral therapy. Mechanistic ancillary studies that leverage existing HIV/AIDS cohorts and clinical trials are encouraged. Areas of interest include, but are not limited to:

• Mechanisms by which HIV infection and/or antiretroviral therapy contribute to osteopenia and osteoporosis.
• Mechanisms by which HIV infection and/or antiretroviral therapy specifically and directly affect skeletal muscle leading to cachexia or weakness.
• Mechanisms by which HIV infection and/or antiretroviral therapy lead to lipoatrophy of the skin.
• Effects of HIV infection and/or antiretroviral therapy on the rheumatic diseases and on autoimmune diseases of skin.
• Effects of HIV infection and/or antiretroviral therapy on the skin barrier, including both the physical barrier as well as regulation of the cutaneous innate and adaptive immune system, and subsequent changes in the skin microbiome that may affect the incidence and/or severity of skin diseases.

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Of particular interest to NICHD are studies of reproductive aging among HIV-infected women, the interaction of reproductive aging and menopause with other HIV-associated complications such as neurocognitive decline and bone changes, behavioral aspects of aging with HIV, impact of stigma, and HIV prevention for aging women. The reproductive tract changes (immunologic, microbiologic, epithelial, etc.) and behavioral changes during and after menopause may increase susceptibility to HIV infection, and older women may not be aware of HIV risk. Novel prevention strategies may be required for older women. In addition, systemic changes with loss of reproductive hormones may alter immune responses and increase development of complications such as osteoporosis which are more common among persons with HIV infection.

National Institute on Drug Abuse (NIDA)

For this initiative, NIDA is interested in understanding the intersection of aging, HIV/AIDS, and the chronic use and abuse of addictive substances, including nicotine, marijuana, narcotics, psychostimulants, prescription drugs, and polysubstance use. Topics relevant to NIDA include but are not limited to:

• epidemiological and clinical observational studies of substance use and HIV progression and response to therapy, including studies of racial, ethnic, and age disparities in the perceptions of aging individuals toward risk and in accessing and using HIV testing and treatment services;
• HIV replication and pathogenesis among older persons, including the medical consequences of HIV and substance use, and of coinfections associated with substance use (e.g. HCV, TB);
• cognitive and neurological complications related to substance abuse and HIV;
• age-specific neuroplastic and neurocognitive changes, preventative and treatment interventions tailored to the special needs and comorbidities experienced among aging populations;
• social, behavioral, and services research relevant to substance use and HIV/AIDS in older populations, including studies of the effects of medical marijuana use on HAART adherence or strategies to improve HAART adherence among persons with multiple comorbidities.

National Institute of Mental Health (NIMH)

The NIMH Division of AIDS Research (DAR) supports research in HIV and aging with special focus on behavioral/psychosocial studies and on basic and clinical NeuroAIDS studies. NIMH is interested in research studies in HIV/aging in the following areas: (1) prevention research in HIV-at risk; (2) optimal treatment of HIV-infected individuals; (3) HIV CNS pathophysiological mechanisms; (4) neuropsychiatric comorbidities. With the successes of effective antiretroviral treatment, HIV-positive patients are living longer, but are at greater risk of developing previously unrecognized long-term complications of HIV infection. Comorbidities are now common in persons on antiretroviral therapy, and as the HIV+ population ages, a greater understanding is needed about the causes and effective management for these comorbidities. Neuropsychiatric comorbidities and others not directly referable to HIV have attracted increased importance for the behavioral and NeuroAIDS research agendas of DAR because they constitute a disease burden equivalent to or greater than HIV-related co-morbidities. Knowledge is critical in the areas enumerated above and in a number of other related areas (e.g., normal aging processes; diseases associated with aging; relevant moderators and mediators; methodologic improvements in subpopulation sampling and behavioral phenotypes). This will provide the foundation for a program of intervention research for HIV/aging which can identify effective prevention or treatment strategies. We encourage longitudinal strategies to help differentiate between the subpopulations of aging, assess developmental trajectories and provide causal explanations. Research designs should go beyond using chronological age alone because HIV, like the process of aging, is shaped more by the individual’s social, physical, cultural, and economic setting than by biological senescence. Examples of relevant research include, but are not limited to:

• Develop and test for aging populations at risk for HIV state of the art behavioral and/or combination biomedical prevention strategies with a focus on integrating these approaches and attending to age-associated comorbidities/ coinfections/complications; and conduct implementation research on scaling up of effective interventions;
• Conduct formative research on determinants of HIV care engagement, antiretroviral adherence, and retention in care among older individuals living with HIV infection; and develop/test interventions to promote care engagement, antiretroviral adherence, and care retention;
• Conduct research in subgroups of older minority populations and other underserved HIV older vulnerable populations (including men who have sex with men and persons with mental health and substance abuse disorders) integrating behavioral, social, and biological factors to understand HIV-related health disparities; and develop/test interventions at all levels of analysis (individual, community, or society);
• Elucidate mechanisms of HIV-associated neuropathogenesis in the context of aging, chronic infection with HIV, and long term exposure to Highly Active Antiretroviral Therapy (HAART) and in light of potential interactions with HAART, neurodegenerative diseases, and aging-related co-morbid conditions;
• Develop novel therapeutic strategies for treatment of HIV-associated neurocognitive impairment in the HIV-positive aging population;
• Identify in HIV-positive aging populations clinical biomarkers linked with HIV-associated CNS disease progression and response to therapy; evaluate neurobehavioral and functional consequences of HIV/AIDS in aging subpopulations; and develop cognitive interventions to improve neurobehavioral function in aging subpopulations.

National Institute of Neurological Disorders and Stroke (NINDS)

NINDS is interested in fostering innovative basic, translational and clinical research on the effects of chronic HIV infection, co-morbidities, and aging on the central nervous system. Research to define and elucidate novel mechanisms of pathogenesis that are driving neurocognitive decline at the intersection of HIV-associated neurodegenerative processes, aging-associated central nervous system disease, chronic HAART treatment effects, and host susceptibility factors are highly encouraged. Areas of research interest include, but not limited to:

• Defining the mechanism of HIV, the effects of HAART, and aging-related co-morbid conditions (e.g. stroke) on cerebrovascular factors that cause neurocognitive impairment;
• Assessing the impact of HIV and aging on neurodegenerative processes;
• Determining the effects of HIV, aging, and HAART on blood brain barrier (BBB) integrity;
• Elucidating mitochondrial dysfunction, dendritic degeneration, and dysregulated axonal transport associated with HIV and aging;
• Evaluating deregulated expression of amyloid-beta, amyloid precursor protein, tau and synuclein as a result of chronic HIV infection in the aging population;
• Studying the impact of HIV on autophagy and clearance of misfolded proteins in neurodegenerative processes;
• Determining the role of neurotrophic factors mediated repair mechanisms in the elderly HIV-infected population;
• Identifying novel molecular markers linked with HIV-associated CNS diseases in the older population;
• Ascertaining potential drug-drug interactions between HAART and other drugs taken by older individuals;
• Studying host genetic factors that alter susceptibility to accelerated HIV-associated aging events that impact on neurocognitive outcomes;
• Investigating the role of HIV-associated co-infections on neurologic disorders in the aging population.

(1) Centers for Disease Control and Prevention, HIV Surveillance Reports, Volumes 17 and 21 (2005 and 2009). http://www.cdc.gov/hiv/surveillance/resources/reports/2005report/ and http://www.cdc.gov/hiv/surveillance/resources/reports/2009report/

(2) CDC Fact Sheet: HIV/AIDS among Persons Aged 50 and Older. http://www.cdc.gov/hiv/topics/over50/resources/factsheets/over50.htm

Funding Instrument	Grant
Application Types Allowed	New Resubmission Revision The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.
Award Budget	The combined budget for direct costs for the two year project period may not exceed $275,000. No more than $200,000 may be requested in any single year. Applicants may request direct costs in $25,000 modules, up to the total direct costs limitation of $275,000 for the combined two-year award period.
Award Project Period	The maximum project period is 2 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• Grants.gov
• eRA Commons

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4-6 weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan..

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Foreign (non-US) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

The Direct Costs in applications for assignment to the National Heart, Lung, and Blood Institute (NHLBI) must not exceed $500,000 in any year.

Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable.

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact/priority score.
• Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD(s)/PI(s) will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

Not Applicable.

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]

Basil A. Eldadah, MD, PhD
National Institute on Aging (NIA)
Telephone: 301-496-6761
Email: [email protected]

Kendall J. Bryant, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-402-9389
Email: [email protected]

Geraldina Dominguez, PhD
National Cancer Institute (NCI)
Telephone: 301-496-3204
Email: [email protected]

Monica R. Shah, MD, MHS, MSJ, FACC
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-594-1079
Email: [email protected]

Robin Huebner, PhD, MPH
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3216
Email: [email protected]

Carl C. Baker, MD, PhD
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5017
Email: [email protected]

D. Heather Watts, MD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6874
Email: [email protected]

Jag Khalsa, Ph.D.
Chief, Medical Consequences of Drug Abuse and Co-occurring Infections Branch
Division of Pharmacotherapies and Medical Consequences of Drug Abuse
National Institute on Drug Abuse, NIH, DHHS
Telephone: 301-443-2159
Fax: 301-443-2599
Email: [email protected]

David M. Stoff, PhD
National Institute of Mental Health (NIMH)
Telephone: 301-443-4625
Email: [email protected]

May Wong, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1431
Email: [email protected]

Robert Freund, PhD
Center for Scientific Review (CSR)
Telephone: 301-435-1050
Email: [email protected]

Robin Laney
National Institute on Aging (NIA)
Telephone: 301-496-1473
Email: [email protected]

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]

Shane Woodward
National Cancer Institute (NCI)
Telephone: 301-496-8791
Email: [email protected]

Ann Marie Brasile Mejac, AA, CRA
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0164
Email: [email protected]

Ann Devine
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: (240) 669-2988
Email: [email protected]

Andy Jones
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-451-0610
[email protected]

Bryan Clark
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: [email protected]

Carol Alderson
National Institute on Drug Abuse (NIDA)
Telephone: 301-933-6196
Email: [email protected]

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: [email protected]

Tijuanna DeCoster, MPA
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.