Advertisement

HIV and Aging

      In the United States the median age of individuals living with HIV infection is approximately 50 years.

      Centers for disease control and prevention. monitoring selected national HIV prevention and care objectives by using HIV surveillance data—United states and 6 dependent areas, 2014. HIV surveillance supplemental report 2016; 21(no. 4). http://www.cdc.gov/hiv/library/reports/surveillance/. published july 2016. accessed [08/1/2016]. CDC.;21(4):49.

      In developing countries improved access to antiretroviral therapy also has prolonged life in people infected with HIV.
      • Mills E.J.
      • Barnighausen T.
      • Negin J.
      HIV and aging--preparing for the challenges ahead.
      This demographic shift has brought the challenges of geriatric medicine to HIV clinical care. The report by Dr. Edward Wing is an informative review of the HIV literature on HIV and Aging {Wing}. The review describes the increased risk for chronic non-AIDS diseases in HIV-infected adults. These age-related diseases are complicated by viral co-infections such as hepatitis C (liver cancer) and human papilloma virus (rectal cancer). The review will help clinicians new to the field of HIV care who find themselves treating geriatric syndromes rather than lipodystrophy syndrome or AIDS wasting syndrome. Whether HIV accelerates aging remains a topic of debate.
      • Effros R.B.
      • Fletcher C.V.
      • Gebo K.
      • et al.
      Aging and infectious diseases: Workshop on HIV infection and aging: What is known and future research directions.
      • Martin J.
      • Volberding P.
      HIV and premature aging: A field still in its infancy.
      • Deeks S.G.
      • Phillips A.N.
      HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity.
      • High K.P.
      • Brennan-Ing M.
      • Clifford D.B.
      • et al.
      HIV and aging: State of knowledge and areas of critical need for research. A report to the NIH office of AIDS research by the HIV and aging working group.
      The arguments for and against accelerated aging in HIV are summarized in the review, which emphasizes the issue of chronic inflammation.
      At any point in life “biologic age” can be affected by an increased rate of aging (accelerated aging) or a cumulative increase in an age-related phenotype (advanced aging).
      • Sorkin J.D.
      • Katzel L.I.
      Methodological problems in research on aging. In: Textbook of geriatric medicine and gerontology.
      These two effects can be seen in a graph from our work in cardiorespiratory fitness (VO2),
      • Oursler K.K.
      • Sorkin J.D.
      • Smith B.A.
      • Katzel L.I.
      Reduced aerobic capacity and physical functioning in older HIV-infected men.
      a benchmark of aging that encompasses changes at the organ and cellular level. We hypothesized that HIV-infected adults would have a greater rate of decline in fitness compared to healthy adults. The data plot of VO2 vs. age in HIV-infected men and age-matched uninfected men showed two parallel lines with the same slope (ΔVO2/Δage) suggesting that the “aging” rate was the same in the two groups. However, across the age span VO2 was 40% lower in the HIV-infected men, suggesting advanced biologic age in men infected with HIV. Does a study's finding of a difference in slopes always represent evidence of accelerated aging; does a constant difference between lines always indicate advanced aging? Before one can answer these questions the study's design needs to be considered. If the data were collected longitudinally then the slope of the line is the change with increasing age. If the data were obtained from a cross-sectional study, then the slope is the difference in the outcome comparing people at different ages. Cross-sectional differences can capture effects due to aging, but they can also be caused by birth cohort effects or selective mortality
      • Sorkin J.D.
      • Katzel L.I.
      Methodological problems in research on aging. In: Textbook of geriatric medicine and gerontology.
      . Wing discusses data from longitudinal cohorts showing that the increased risk of comorbid conditions associated with HIV does not change overtime,
      • Althoff K.N.
      • McGinnis K.A.
      • Wyatt C.M.
      • et al.
      Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer in HIV-infected versus uninfected adults.
      • Rasmussen L.D.
      • May M.T.
      • Kronborg G.
      • et al.
      Time trends for risk of severe age-related diseases in individuals with and without HIV infection in denmark: A nationwide population-based cohort study.
      which supports a process of advanced aging rather than accelerated aging. An additional important consideration in clinical research in aging is the composition of the comparison group. HIV offers additional challenges in selecting a comparison group since infection with HIV is associated with other viral infections and lifestyle factors such as smoking, alcohol and drug use that alone have an impact on the aging process
      • Wong C.
      • Althoff K.
      • Gange S.J.
      Identifying the appropriate comparison group for HIV-infected individuals.
      . If HIV acts as an effect modifier in these relationships then adjustment for confounders and competing risks is required.
      These methodological challenges are not new for studies of geriatric populations with multimorbidity. Gerontologists have recognized that the aging process is composed of three types of aging, pure biologic aging (changes programmed into our genome), secondary aging (changes that occur as a result of environmental influences such as a sedentary lifestyle), and tertiary aging (the increased incidence and prevalence of disease as we get older).
      • Sorkin J.D.
      • Katzel L.I.
      Methodological problems in research on aging. In: Textbook of geriatric medicine and gerontology.
      When presented with a statement that some outcome is age-related, it is imperative to determine if the results are due fundamentally to primary, secondary or tertiary aging. Benefits of compartmentalizing the aging process in this manner is that it allows one to consider the interplay of aging mechanisms across different patient populations and focus on effective interventions that will attenuate the age-related outcome of interest. Exercise, a lifestyle intervention that targets secondary aging, is a low-cost, low-risk intervention that has salutary effects on the biological mechanisms of aging discussed in Wing's review
      • Porter Starr K.N.
      • McDonald S.R.
      • Bales C.W.
      Obesity and physical frailty in older adults: A scoping review of lifestyle intervention trials.
      and further can prevent as well as treat many comorbid conditions.
      • Chodzko-Zajko W.J.
      • Proctor D.N.
      • Fiatarone Singh M.A.
      • et al.
      American college of sports medicine position stand. exercise and physical activity for older adults.
      Although exercise improves fitness, strength, and quality of life and decreases cardiometabolic disease and depression in HIV-infected adults without adverse effect on immune function,
      • O’Brien K.K.
      • Tynan A.
      • Nixon S.A.
      • Glazier R.H.
      Effectiveness of aerobic exercise for adults living with HIV: Systematic review and meta-analysis using the cochrane collaboration protocol.
      • Gomes-Neto M.
      • Conceicao C.S.
      • Oliveira C.V.
      • Brites C.
      A systematic review of the effects of different types of therapeutic exercise on physiologic and functional measurements in patients with HIV/AIDS.
      it has yet to become part of the strategy for long-term care of HIV-infected adults.
      • d’Ettorre G.
      • Ceccarelli G.
      • Giustini N.
      • Mastroianni C.M.
      • Silvestri G.
      • Vullo V.
      Taming HIV-related inflammation with physical activity: A matter of timing.
      The review highlights the challenges in the management of older HIV patients. Guidelines for managing newly diagnosed HIV patients over 50 years of age are provided in Table 1 and suggestions for adapting screening practices in the chronic care of HIV-infected adults 50+ years of age are discussed further in the text. Additional cancer screening includes a yearly anal Pap testing for high risk sub-groups.
      • Aberg J.A.
      • Gallant J.E.
      • Ghanem K.G.
      • Emmanuel P.
      • Zingman B.S.
      • Horberg M.A.
      Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the infectious diseases society of america.
      Screening for osteoporosis is recommended to start at age 50 in HIV-infected men.
      • Brown T.T.
      • Hoy J.
      • Borderi M.
      • et al.
      Recommendations for evaluation and management of bone disease in HIV.
      This age-based recommendation in men regardless of other risk factors is significantly different than the general male population and highlights the need for clinicians to consider geriatric problems in HIV-infected patients.
      Frailty is well studied in the geriatric and HIV literature as a phenotype with different components that constitute it as a geriatric syndrome
      • Walston J.
      • Hadley E.C.
      • Ferrucci L.
      • et al.
      Research agenda for frailty in older adults: Toward a better understanding of physiology and etiology: Summary from the american geriatrics society/national institute on aging research conference on frailty in older adults.
      • Levett T.J.
      • Cresswell F.V.
      • Malik M.A.
      • Fisher M.
      • Wright J.
      Systematic review of prevalence and predictors of frailty in individuals with human immunodeficiency virus.
      and is an important component of Wing's review. Similar to lipodystrophy syndrome, research in frailty suffers due to the diverse definitions of the syndrome. A frequently used phenotype of the frailty syndrome, developed and validated by Fried et al. in older community dwelling HIV negative adults 65+ years of age, includes weight loss as one of its properties.
      • Fried L.P.
      • Tangen C.M.
      • Walston J.
      • et al.
      Frailty in older adults: Evidence for a phenotype.
      In this population, weight loss primarily captures the loss of muscle mass due to age-related sarcopenia.
      • Cruz-Jentoft A.J.
      • Baeyens J.P.
      • Bauer J.M.
      • et al.
      Sarcopenia: European consensus on definition and diagnosis: Report of the european working group on sarcopenia in older people.
      Frailty research conducted in younger adults with and without HIV will capture weight loss that is more likely to be cachexia, loss of body mass because of a disease process. The difference between age-related sarcopenia and cachexia is nicely described by William Evans.
      • Evans W.J.
      Skeletal muscle loss: Cachexia, sarcopenia, and inactivity.
      The blanket application of geriatric syndromes developed for and in elderly adults may produce different results when applied to older HIV-infected adults, who chronologically still represent a middle-aged population. Rather than studying a geriatric syndrome like frailty, targeting a specific problem such as low muscle mass or slow gait speed in research in HIV and aging will result in less heterogeneity of results and quicker translation to a specific, and effective, intervention. While clinical care strategies for older HIV-infected adults are validated and translated to guidelines, clinicians can evaluate their patients’ functional status, the capacity to perform activities independently. Functional status is a standard geriatric assessment that can be easily measured by questionnaire or functional performance testing in the outpatient clinic and has been advocated for older HIV-infected adults.
      • High K.P.
      • Bradley S.
      • Loeb M.
      • Palmer R.
      • Quagliarello V.
      • Yoshikawa T.
      A new paradigm for clinical investigation of infectious syndromes in older adults: Assessment of functional status as a risk factor and outcome measure.
      • Greene M.
      • Justice A.C.
      • Lampiris H.W.
      • Valcour V.
      Management of human immunodeficiency virus infection in advanced age.
      The identified physical and mental limitations can alert clinicians to refer patients for comprehensive geriatric evaluation.

      References

      1. Centers for disease control and prevention. monitoring selected national HIV prevention and care objectives by using HIV surveillance data—United states and 6 dependent areas, 2014. HIV surveillance supplemental report 2016; 21(no. 4). http://www.cdc.gov/hiv/library/reports/surveillance/. published july 2016. accessed [08/1/2016]. CDC.;21(4):49.

        • Mills E.J.
        • Barnighausen T.
        • Negin J.
        HIV and aging--preparing for the challenges ahead.
        N Engl J Med. 2012; 366: 1270-1273
        • Effros R.B.
        • Fletcher C.V.
        • Gebo K.
        • et al.
        Aging and infectious diseases: Workshop on HIV infection and aging: What is known and future research directions.
        Clin Infect Dis. 2008; 47: 542-553
        • Martin J.
        • Volberding P.
        HIV and premature aging: A field still in its infancy.
        Ann Intern Med. 2010; 153: 477-479
        • Deeks S.G.
        • Phillips A.N.
        HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity.
        BMJ. 2009; 338: a3172
        • High K.P.
        • Brennan-Ing M.
        • Clifford D.B.
        • et al.
        HIV and aging: State of knowledge and areas of critical need for research. A report to the NIH office of AIDS research by the HIV and aging working group.
        J Acquir Immune Defic Syndr. 2012; 60: 1
        • Sorkin J.D.
        • Katzel L.I.
        Methodological problems in research on aging. In: Textbook of geriatric medicine and gerontology.
        5th ed. Churchill Livingstone, London1998
        • Oursler K.K.
        • Sorkin J.D.
        • Smith B.A.
        • Katzel L.I.
        Reduced aerobic capacity and physical functioning in older HIV-infected men.
        AIDS Res Hum Retroviruses. 2006; 22: 1113-1121
        • Althoff K.N.
        • McGinnis K.A.
        • Wyatt C.M.
        • et al.
        Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer in HIV-infected versus uninfected adults.
        Clin Infect Dis. 2015; 60: 627-638
        • Rasmussen L.D.
        • May M.T.
        • Kronborg G.
        • et al.
        Time trends for risk of severe age-related diseases in individuals with and without HIV infection in denmark: A nationwide population-based cohort study.
        Lancet HIV. 2015; 2 (Accessed Nov 7, 2016): 288
        • Wong C.
        • Althoff K.
        • Gange S.J.
        Identifying the appropriate comparison group for HIV-infected individuals.
        Curr Opin HIV AIDS. 2014; 9: 379-385
        • Porter Starr K.N.
        • McDonald S.R.
        • Bales C.W.
        Obesity and physical frailty in older adults: A scoping review of lifestyle intervention trials.
        J Am Med Dir Assoc. 2014; 15: 240-250
        • Chodzko-Zajko W.J.
        • Proctor D.N.
        • Fiatarone Singh M.A.
        • et al.
        American college of sports medicine position stand. exercise and physical activity for older adults.
        Med Sci Sports Exerc. 2009; 41: 1510-1530
        • O’Brien K.K.
        • Tynan A.
        • Nixon S.A.
        • Glazier R.H.
        Effectiveness of aerobic exercise for adults living with HIV: Systematic review and meta-analysis using the cochrane collaboration protocol.
        BMC Infect Dis. 2016; 16: 182
        • Gomes-Neto M.
        • Conceicao C.S.
        • Oliveira C.V.
        • Brites C.
        A systematic review of the effects of different types of therapeutic exercise on physiologic and functional measurements in patients with HIV/AIDS.
        Clinics (Sao Paulo). 2013; 68: 1157-1167
        • d’Ettorre G.
        • Ceccarelli G.
        • Giustini N.
        • Mastroianni C.M.
        • Silvestri G.
        • Vullo V.
        Taming HIV-related inflammation with physical activity: A matter of timing.
        AIDS Res Hum Retroviruses. 2014; 30: 936-944
        • Aberg J.A.
        • Gallant J.E.
        • Ghanem K.G.
        • Emmanuel P.
        • Zingman B.S.
        • Horberg M.A.
        Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the infectious diseases society of america.
        Clin Infect Dis. 2014; 58: 1-10
        • Brown T.T.
        • Hoy J.
        • Borderi M.
        • et al.
        Recommendations for evaluation and management of bone disease in HIV.
        Clin Infect Dis. 2015; 60: 1242-1251
        • Walston J.
        • Hadley E.C.
        • Ferrucci L.
        • et al.
        Research agenda for frailty in older adults: Toward a better understanding of physiology and etiology: Summary from the american geriatrics society/national institute on aging research conference on frailty in older adults.
        J Am Geriatr Soc. 2006; 54: 991-1001
        • Levett T.J.
        • Cresswell F.V.
        • Malik M.A.
        • Fisher M.
        • Wright J.
        Systematic review of prevalence and predictors of frailty in individuals with human immunodeficiency virus.
        J Am Geriatr Soc. 2016; 64: 1006-1014
        • Fried L.P.
        • Tangen C.M.
        • Walston J.
        • et al.
        Frailty in older adults: Evidence for a phenotype.
        J Gerontol A Biol Sci Med Sci. 2001; 56: M156
        • Cruz-Jentoft A.J.
        • Baeyens J.P.
        • Bauer J.M.
        • et al.
        Sarcopenia: European consensus on definition and diagnosis: Report of the european working group on sarcopenia in older people.
        Age Ageing. 2010; 39: 412-423
        • Evans W.J.
        Skeletal muscle loss: Cachexia, sarcopenia, and inactivity.
        Am J Clin Nutr. 2010; 91: 1127S
        • High K.P.
        • Bradley S.
        • Loeb M.
        • Palmer R.
        • Quagliarello V.
        • Yoshikawa T.
        A new paradigm for clinical investigation of infectious syndromes in older adults: Assessment of functional status as a risk factor and outcome measure.
        Clin Infect Dis. 2005; 40: 114-122
        • Greene M.
        • Justice A.C.
        • Lampiris H.W.
        • Valcour V.
        Management of human immunodeficiency virus infection in advanced age.
        JAMA. 2013; 309: 1397-1405

      Linked Article