1Co-sponsored by the National Institute on Aging, National Institute on Drug Abuse, Office of Rare Diseases
From the aNational Institute of Mental Health, Center for Mental Health Research on AIDS, Bethesda, Maryland, USA, the bNational Institute on Drug Abuse, Bethesda, Maryland, USA, the cNational Institute on Aging, Bethesda, Maryland, USA, and the dDepartment of Neurology, OLVG Hospital, Amsterdam, the Netherlands.
The views expressed are those of the authors and do not necessarily reflect the official position of the National Institute of Mental Health, National Institute on Aging, National Institute on Drug Abuse, Office of Rare Diseases or any other part of the U.S. Department of Health and Human Services.
This supplement to AIDS is dedicated to research on CNS-related comorbidities and complications in HIV-infected older adults as discussed at the National Institute of Mental Health workshop (`Mental Health Research Issues in HIV Infection and Aging') held in Washington, D.C., in April, 20021. As we witness unprecedented population growth of older Americans, the face of the HIV/AIDS epidemic in the United States continues to evolve with rising concern about HIV infection in later life. Even as new AIDS cases and deaths continue to decline, there has been an increase in the prevalence of HIV infection among older adults. People living with HIV disease are growing older and living longer due to the emergence of highly active antiretroviral therapy (HAART) which has prolonged survival for HIV-infected individuals who are now living well into their 50s, 60s and 70s. There are currently more than 60 000 persons estimated to be aged 50 years or older living with AIDS in the United States (Mack and Ory, 2003). A growing number of older people are newly infected with HIV. The number of persons 65 years of age and older at AIDS diagnosis has grown 10-fold in the last 10 years (from 1008 to 10 002). Between 1991 and 1996, the number of new AIDS cases rose twice as fast in persons 50 plus years of age than it did in persons younger than 50 (22% vs 9%, respectively; Centers for Disease Control and Prevention (CDC), 1998). According to the CDC, reported rates of persons living with AIDS suggest that older adults account for up to 15% of AIDS cases, representing an increase of about 5% from 1997-1999, and this percentage is expected to continue to grow.
A key issue in the study of HIV/AIDS and aging is to identify and characterize the ways in which older adults differ from younger adults and suggest the underlying mechanisms that might account for these differences. Compelling evidence exists that natural history and symptom manifestations of HIV infection in the elderly substantially differ from those seen in younger cohorts. Relative to their younger counterparts, older adults living with HIV/AIDS have a more severe HIV disease course and a shorter survival rate; have less desirable health indices at diagnosis (e.g. lower CD4+ cell counts); have shorter AIDS-free intervals; have a higher number of opportunistic infections and have earlier development of tumors and lesions. These differences between older and younger HIV-infected adults could be due to immunosenescence; the presence of underlying conditions associated with aging; the existence of current and/or past history of drug abuse; HIV-related medical sequelae and CNS complications; and the adverse effects of certain medical treatments. Research is needed to determine the mechanisms at work in an aging immune system and to determine whether there is a difference in immune reconstitution following HAART between younger and older HIV-infected populations and how this difference might impact the development of CNS disease and neurocognitive dysfunction.
One of the most important research questions in the study of HIV/AIDS and aging is to distinguish and understand the interactions among concomitant and overlapping conditions including HIV disease, comorbidities (HIV-related and non HIV-related), normal aging, age-related medical changes and age-related diseases. For example, older Americans have their own population-specific health challenges, such as Alzheimer's disease, osteoporosis, adult-onset diabetes, prostrate cancer, and hypertension and it will be necessary to distinguish the impact of such age-related diseases from the direct effects of aging. Moreover, there is even evidence that an interaction between HIV-induced pathophysiologies and Alzheimer's disease-related pathophysiologies may be occurring and this interaction would have important implications for aging. HIV risk may also be intensified by a pre-existing compromised immune system caused by other health problems, drug abuse or the aging process itself. Aging is also associated with changes in body composition, energy and protein metabolism and it is well known how age-related loss of total body protein also impacts negatively on immunity and quality of life. Furthermore, as HIV-infected persons age, new patterns in cancer incidence may emerge as well as increased infections and mortality, and aging itself may lead to changes in the immune system and result in a loss of T cells leading to AIDS symptoms.
As the population of people with HIV infection and AIDS is aging, the overall profile of HIV-associated comorbidities and complications has changed dramatically. People with HIV infection are now living long enough to experience HIV as a chronic disease with competing risks from aging, drug toxicity and comorbid diseases and conditions. With the increasing prevalence of general medical and neuropsychiatric comorbidities as HIV infected persons are living longer, it is becoming clear that these comorbidities now constitute at least an equivalent disease burden for aging HIV infected persons as are HIV-related conditions. Because we are in the midst of a new wave of the HIV epidemic in which new conditions are emerging and the etiologies of patient outcomes are likely to be multifaceted, a new set of questions now needs to be addressed. For example, we will need to determine whether these comorbidities that increase with age and with HIV infection are synergistic and if so, the mechanism driving the synergism. It will also be important to determine the consequences of long term exposure to HIV treatment and how, and to what extent, treatment interacts with these comorbidities. The neurocognitive and neuropsychiatric comorbidities are considered key factors as HIV-infected persons age because of their effect on quality of life and their likely impact on adherence to HIV and general medical treatment.
In the present supplement, the individual contributions are first introduced in the context of important research areas and questions in the field (Stoff, this issue). This is followed by separate sections on neurocognitive aspects (Becker et al., Hinkin et al., Cherner et al.); neuropsychiatric aspects (Dolder et al., Rabkin et al., Justice et al.); and neuropathogenesis (Ernst and Chang, Arango et al., Brew, Valcour et al., Goodkin et al.). The wide range of issues covered in this supplement will serve to articulate the state of the art in the emergent research area of HIV/AIDS and aging and will help to identify scientific opportunities and a plan for moving the field forward.
1. Centers for Disease Control and Prevention. AIDS among persons aged greater than 50 years—United States, 1991–1996. MMWR 1998, 47:21–27.
2. Mack, K and Ory M. AIDS and older Americans at the end of the twentieth century. J Acquir Immune Defic Synd 2003, 33(2): S68–S75.
3. Stoff, D.M. Mental health research issues in HIV/AIDS and aging: problems and prospects. This issue.