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National HIV/AIDS and Aging Awareness Day
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"biomedical and public health communities face new challenges at the intersection of HIV and aging"
"It is imperative that we in the research community decipher the medical implications of aging with HIV and continue developing more sophisticated treatment approaches so these older adults can live longer, healthier lives."
"researchers with the Multicenter AIDS Cohort Study have shown that HIV infection accelerates the development of frailty, a condition of the elderly that makes people more vulnerable to illness, injury and death. Scientists now want to determine which HIV-infected individuals are at highest risk for developing HIV-associated frailty with the hope of identifying factors to mitigate or prevent its development"
September 18, 2009
Statement of Anthony S. Fauci, M.D.
Director, National Institute of Allergy and Infectious Diseases
Richard J. Hodes, M.D.
Director, National Institute on Aging
and
Jack Whitescarver, Ph.D.
Director, NIH Office of AIDS Research
National Institutes of Health
HIV/AIDS began its deadly course in the United States mostly as a disease of young men, but today the epidemic touches people of all ages, including adults aged 50 and older. On September 18, the first National HIV/AIDS and Aging Awareness Day, we pause to recognize the importance of preventing HIV infection in this age group and understanding and addressing the unique health effects of the virus on older Americans.
Thanks to the advent of potent, multi-drug therapy against HIV in the mid-1990s, many HIV-infected Americans are living into their 50s and well beyond. Also, while the majority of new HIV infections are in younger Americans, individuals 50 years of age and older accounted for approximately 10 percent of all new HIV infections in the United States in 2006.1 As a consequence of these trends, approximately one quarter of HIV-infected adults in the United States in 2007 were at least 50 years old.2
Older adults with long-term or new HIV infection experience complex interactions among HIV, antiretroviral therapy, age-related changes to the body, and, often, treatment for illnesses associated with aging. These interactions affect the health care needs and quality of life of older adults. It is imperative that we in the research community decipher the medical implications of aging with HIV and continue developing more sophisticated treatment approaches so these older adults can live longer, healthier lives.
It also is critical to prevent new HIV infections in older Americans by educating them about the importance of routine HIV testing and early diagnosis; how the virus is transmitted; behaviors that place them at risk for acquiring or transmitting the virus; and strategies, such as condom use and needle exchange, that can reduce their risk. Since early diagnosis of HIV is key to optimal treatment, the Centers for Disease Control and Prevention recommends routine HIV testing for all adults up to age 64.3 CDC also recommends HIV testing at least annually for adults aged 64 and over who have risk factors for HIV infection, such as injection drug use.
The U.S. Department of Health and Human Services this month proposed that Medicare cover HIV screening tests for beneficiaries at increased risk for acquiring the virus, including women who are pregnant, and Medicare beneficiaries of any age who voluntarily request the service. Medicare provides health insurance coverage to people who are aged 65 and over or who meet other special criteria.
Aging is an important and expanding focus of HIV/AIDS research at the National Institutes of Health and the NIH-sponsored Centers for AIDS Research. The National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, funds a range of studies to understand the biology of HIV infection in older adults with the goal of improving their medical care. Scientists are studying the interaction between HIV and aging in areas as diverse as diseases of the liver, kidney, brain, heart and lung; cancer; bone density; physical activity; mental health; balance; hearing; response to antiretroviral therapy; immune function; and adherence to medical care.
For example, researchers with the Multicenter AIDS Cohort Study have shown that HIV infection accelerates the development of frailty, a condition of the elderly that makes people more vulnerable to illness, injury and death. Scientists now want to determine which HIV-infected individuals are at highest risk for developing HIV-associated frailty with the hope of identifying factors to mitigate or prevent its development. NIAID and the National Institute on Aging (NIA), also part of NIH, are planning a workshop for late 2009 to identify current knowledge and research gaps in the areas of HIV and frailty, bone health, muscle health and vitamin D production.
Still, many gaps remain in scientific knowledge about the effects of HIV and antiretroviral therapy on aging. To that end, NIAID, NIA, the National Institute of Mental Health and the National Institute of Nursing Research, all part of NIH, are soliciting research proposals to explain and prevent a spectrum of biomedical problems faced by older adults with HIV infection. More information about these funding opportunities is available at
http://grants.nih.gov/grants/guide/pa-files/PA-09 018.html,
http://grants.nih.gov/grants/guide/pa-files/PA-09-019.html, and
http://grants.nih.gov/grants/guide/pa-files/PA-09-017.html.
When AIDS and then its cause-HIV-were recognized in the early 1980s, no one imagined that individuals with HIV infection would eventually survive for decades. Now, with a quarter of the HIV-infected U.S. population age 50 years and older, the biomedical and public health communities face new challenges at the intersection of HIV and aging. In the absence of a cure for HIV, this first annual National HIV/AIDS and Aging Awareness Day marks an opportunity to rededicate ourselves to research aimed at preventing HIV infection in older adults and improving the health and quality of life of those who are infected.
Dr. Fauci is director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health in Bethesda, Maryland.
Media inquiries can be directed to the NIAID Office of Communications at 301-402-1663, niaidnews@niaid.nih.gov.
NIAID conducts and supports research-at NIH, throughout the United States, and worldwide-to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
The National Institutes of Health (NIH)-The Nation's Medical Research Agency-includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visithttp://www.nih.gov.
References :
1. HI Hall et al. 2008. Estimation of HIV incidence in the United States. JAMA 300:520-529.
2. CDC. 2008. HIV prevalence estimates-United States, 2006. MMWR 57:1073-1076.
3. CDC. 2006. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR 55(RR-14):7. Available atwww.cdc.gov/mmwr/PDF/rr/rr5514.pdf (PDF).
Background
Over the past decades, there has been a dramatic increase in the number of older persons with HIV infection and/or AIDS. This increase derives from two sources: (1) a growing number of cases newly diagnosed in older persons, and (2) recent improvements in antiretroviral therapy, with cases diagnosed at younger ages surviving into older age. From 2000 to 2004, CDC reports that the proportion of AIDS patients 50+ years old rose from 19% to 27% and the number of older adults 50+ years living with HIV infection and/or AIDS more than doubled. Importantly, for that surveillance period, persons ages 40-49 years had the highest prevalence of HIV/AIDS and the steepest rise in prevalence. Thus the number of older people with HIV/AIDS is expected to increase even further during the next decade as this "younger" group survives with current treatment and moves into the "older" age group. It is projected that, by 2015, more than half of all HIV-infected individuals in the U.S. will be over the age of 50.
The clinical presentations of the two groups of older HIV/AIDS patients may differ significantly. Older persons with new infections may experience side effects of disease and treatment superimposed on existing medical conditions or multiple morbidities. In addition, a greater proportion of "new" cases in the older age group are diagnosed with both HIV and AIDS at presentation, as early symptoms associated with HIV may be dismissed as signs of "growing old." Younger adults aging with HIV on prolonged treatment with HAART frequently experience long-term side effects of disease and treatment that mimic or accelerate aging processes (e.g., age-related changes in immune function, early bone mineral loss, and accelerated age-associated conditions such as atherosclerosis). Nonetheless, medical issues facing both groups involve complex interactions among age-related changes in physiologic processes, polytrophic effects of HIV, and multisystem activities of antiretroviral therapy, with significant impact on functional outcomes, and quality of life, and health care needs.
To address these issues in clinical and translational aspects of health care for older patients with HIV/AIDS, the Association of Specialty Professors, the Infectious Diseases Society of America, the HIV Medical Association, the National Institutes on Aging (NIA) and Allergy and Infectious Diseases (NIAID) organized a workshop October 2007 to review what is known in HIV and aging, identify research gaps, and suggest high priority areas for future research A summary of Workshop recommendations entitled "Workshop on HIV and Aging: What is Known and Future Research Directions," was published in the August 15, 2008 issue of Clinical Infectious Diseases ( Effros RB, Fletcher CV, Gebo K et al, Clinical Infectious Diseases 47:542-53, 2008). This FOA builds on the recommendations of this Workshop to promote clinical and translational research in these areas.
Scope of Research
This FOA invites patient-oriented, clinical and translational research applications addressing the inter-relationship of HIV/AIDS to aging or old age, building at the interface of basic and clinical approaches. Projects proposed in response to this initiative should have potential clinical applications in balancing strategies to slow the progression in HIV infection in older patients and to optimize functional status and quality of life outcomes.
Although a wide range of research on HIV/AIDS will likely lead to benefits for older persons, this FOA is confined to topics concerning the relationship of HIV infection and AIDS to aging or old age. Studies whose research goals are in one or more of the following areas are within the scope of this initiative: (1) to determine the effects of age-related changes or aging mechanisms on specific aspects of HIV/AIDS (risk, etiology, progression, diagnosis, symptoms, response to treatment, etc); (2) to determine age-related differences in these specific aspects of HIV/AIDS and/or the factors responsible for them; (3) to obtain currently missing information about these specific aspects of HIV/AIDS in very old people or older people with comorbidities; and (4) to develop or test new methods or technologies relevant to 1-3 above .
Areas of interest include, but are not limited to the following:
1. Immune Function and Host Defenses. Changes in immune function and host defenses occur with both aging and HIV infection. Little is known about whether or how age-related changes in immune function contribute to initial presentation or clinical course of HIV infection in older or aging patients, particularly in the areas of T-cell function and cytokinemia; mucosal immunity and gastrointestinal lymphoid tissue; and resistance to other chronic viral infections. To what extend does the spectrum of immune dysregulation from early- to old- old age influence the clinical course of HIV /AIDS? Can interventions targeted at modifying age-associated changes in immune function (e.g., exercise; thymic reconstitution) alter the progression of disease in older patients?
2. Response to Treatment. Age-related differences in response to HAART have been observed with respect to CD4 response and viral clearance but are otherwise largely unexplored. Can physiologic or functional measures be used to identify subgroups of older patients who respond differently to the same regimen or for whom alternative regimen give improved outcomes? To what extent do comorbid conditions or processes (and/or their therapies) influence age-related differences in response?
3. Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics. Age-related changes in multiple physiologic processes may alter the bioavailability, absorption, metabolism, tissue distribution, and excretion of various drugs and their metabolites. To what extent do age-related changes in pharmacokinetics, pharmacodynamics, and pharmacogenomics of antiretroviral agents and related medications influence response to HAART? To what extent do (or should) these considerations influence the response to HAART; the development of adverse events or long-term complications; interactions among drugs or co-existing conditions; or the selection of alternative HAART components?
4. Metabolic Complications of HIV/AIDS. Metabolic implications of aging, HIV, and HAART share common themes in the development of insulin resistance and diabetes; abnormal lipids and atherosclerotic cardiovascular disease (ASCVD); cardiomyopathy; renal insufficiency and chronic kidney disease (CKD); metabolic bone disease; and liver disease marked by severe fibrosis and hepatoma. The interactions of aging processes with HIV, viral actions, or drug effects in the development of metabolic complications of HIV/AIDS and its therapy are an area of current research interest. To what extent are these complications related to aging, HIV, or drug effects? Could HIV be protective for certain metabolic complications (e.g., abnormal lipids) through disease-related symptoms (e.g., cachexia and weight loss) while exacerbating others (e.g., bone mineral loss)? Can physiologic, functional, or therapeutic factors be used to identify subgroups of older patients at increased risk for these complications? Could modification of medical management mitigate or prevent their development?
5. Neurologic Complications of HIV/AIDS. HIV may interact with risk factors for cardiovascular disease, diabetes, and Alzheimer's disease to accelerate mild cognitive impairment, cognitive decline, and dementia in older patients. Recent studies suggest that older patients with HIV and the Apoliporotein E4 allotype may have abnormal accumulations of amyloid, impaired white matter integrity, and enhanced likelihood of development of HIV-related dementia, as well as decreased survival times and increased risk of infectivity. What are the underlying mechanisms of these interactions and how do current and new therapies modulate them to protect from (or increase likelihood of) these complications? Of HIV/AIDS-related complications in the peripheral nervous system?
6. Neuropsychiatric Complications of HIV/AIDS. Recent trends have been noted for an increasing prevalence of neuropsychiatric non-HIV related comorbidities which may in fact be more common than the general medical HIV-related comorbidities. Neuropsychiatric comorbidities are key complicating factors that must be addressed because they affect HIV disease progression among older persons living with HIV/ADS. Such comorbidities may not only decrease immunologic function but more generally impair one's ability to carry out the more demanding activities of daily living. Treatment research targeted towards neuropsychiatric comorbidities requires an understanding of the underlying mechanisms impacting on immunologic deficits to produce neuropsychiatric complications that may arise in older adult HIV patients as a result of both HIV infection and antiretroviral treatment. Given possible interactions between antiretroviral agents, psychiatric drug treatments, and medications for comorbid disorders, the potential for multiple drug-drug interactions is great. How do etiologies of neuropsychiatric comorbidities, aging and medical illnesses overlap and interact in older HIV-infected individuals? How can this knowledge be used to optimize psychiatric and medical care for this group of older patients?
7. HIV-related Malignancies. The development of specific HIV-related malignancies signals the diagnosis of AIDS for many patients. While other cancers are recognized as HIV-related, the full spectrum of HIV-associated premalignant changes and malignancies and their relationship to aging processes is an area for new research. To what extent and through which mechanisms do aging processes contribute to the development of are HIV-related malignancies and/or premalignancies, or to their response to therapy? Are interventions targeting usual pathways of carcinogenesis (e.g., chemoprevention) useful in this setting?
8. Frailty and Functional Status. The development of frailty and functional limitations are common to both aging and HIV infection and may profoundly impact quality of life. What is the pathogenesis of frailty in HIV, and how does this relate to the concept of frailty associated with aging? How are age-relates changes in body composition affected by HIV and its treatment, both subclinically and in recognized HIV-related conditions (e.g., lipodystrophy)? What is the impact of HIV and its therapy on functional status, energy balance, and exercise tolerance in older patients at both clinical and mechanistic levels - for example, what is the role of mitochondrial toxicity due to HIV infection or its treatment in age-related sarcopenia and muscle function?
9. Complexity of Care. Medical care for older patients with multiple conditions is often complex, and the addition of HIV as a comorbidity augments this complexity. Current HIV infection treatment paradigm is complicated for older patients, with multiple drugs and dosing regimen superimposed on those for existing medical problems or augmented by regimen to counteract treatment effects (e.g., lipid abnormalities). Should the treatment paradigm change for older patients, particularly those with comorbidities? Can interventions directed toward coordinating or simplifying care improve medical, functional, and quality of life outcomes in older patients with HIV/AIDS?
Age ranges for "elderly" patients are not specified for this FOA. Age ranges of persons selected for study should support the study hypothesis and effectively utilize the demographic composition of available patient groups, study cohorts or data sets. However, for most projects, research question(s) should target persons 50 years of age or older, consistent with the Centers for Disease Control (CDC) definition of "older" HIV patients. Younger age groups may be included for comparison purposes. The study population(s) and control group(s) should be well defined within a particular treatment setting, community, or general population; settings may include hospitals, nursing homes, other health care environments, and/or outpatient medical practice.
Projects should have both basic and clinical components clearly linked through study design and clear relevance to or potential for application in clinical management of older patients. Applications proposing to incorporate basic research findings in HIV/aging into clinical applications ("bench to bedside") should describe the potential of the findings to improve current clinical approaches, and those exploring clinical observations or questions in HIV/AIDS management at the through basic or molecular techniques ("bedside to bench") should discuss the potential added value of the knowledge gained to clinical issues and health care for older HIV/AIDS patients. Research teams with expertise in appropriate areas of both Geriatrics and Infectious Diseases are strongly recommended for all applications to this FOA, and interactive collaborations between clinical and basic researchers are strongly encouraged.
Potential outcomes should be appropriate for the study question and may include intermediate markers of HIV/AIDS status (surrogate endpoint biomarkers); clinical or biochemical measures of disease status for HIV, treatment-related conditions, and comorbid diseases; traditional outcomes in HIV/AIDS research (viral clearance or load, survival, mortality); and functional status, physical performance, and quality of life.
This FOA does not support Phase III treatment clinical trials or large observational studies per se. However, applicants are encouraged to build on treatment or observational cohorts through ancillary studies and/or to augment data from clinical studies with additional molecular, physiological, or performance measures. The use of other existing resources and cohorts or aging data sets appropriately expanded to address the study question(s) is also encouraged.
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