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Cited by 522HIV-related health complications and treatmentsHIV Research and TreatmentHIV/AIDS Research and Interventions

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

Open access
High, Kevin P., Brennan-Ing, Mark, Clifford, David B., Cohen, Mardge H., Currier, Judith, Deeks, Steven G., Deren, Sherry, Effros, Rita B. +15 more·2012·JAIDS Journal of Acquired Immune Deficiency Syndromes
DOI 10.1097/qai.0b013e31825a3668PMC PMC3413877
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Abstract

HIV risk behaviors, susceptibility to HIV acquisition, progression of disease after infection, and response to antiretroviral therapy all vary by age. In those living with HIV, current effective treatment has increased the median life expectancy to >70 years of age. Biologic, medical, individual, social, and societal issues change as one ages with HIV infection, but there has been only a small amount of research in this field. Therefore, the Office of AIDS Research of the National Institutes of Health commissioned a working group to develop an outline of the current state of knowledge and areas of critical need for research in HIV and Aging; the working groups' findings and recommendations are summarized in this report. Key overarching themes identified by the group included the following: multimorbidity, polypharmacy, and the need to emphasize maintenance of function; the complexity of assessing HIV versus treatment effects versus aging versus concurrent disease; the inter-related mechanisms of immune senescence, inflammation, and hypercoagulability; the utility of multivariable indices for predicting outcomes; a need to emphasize human studies to account for complexity; and a required focus on issues of community support, caregivers, and systems infrastructure. Critical resources are needed to enact this research agenda and include expanded review panel expertise in aging, functional measures, and multimorbidity, and facilitated use and continued funding to allow long-term follow-up of cohorts aging with HIV.

AI snapshot

Written from the paper’s full text.

TL;DR

This NIH Office of AIDS Research working group white paper summarizes knowledge and research priorities for HIV and aging, emphasizing multimorbidity, polypharmacy, functional decline, immune senescence/inflammation/hypercoagulability, and psychosocial/infrastructure needs. It calls for human studies, better biomarkers/indices, cohort follow-up, and geriatric-informed care as the HIV population ages.

Key findings

  • Effective ART has increased median life expectancy to >70 years, and by 2015 half of people living with HIV in the United States will be ≥50 years old; a 20-year-old initiating ART may have already lost 1/3 of expected remaining years of life compared with demographically similar HIV-uninfected persons.
  • HIV-associated, non-AIDS (HANA) conditions—cardiovascular disease, cancers, osteopenia/osteoporosis, liver disease, renal disease, and neurocognitive decline—are increasingly common and linked to aging and chronic inflammation; whether HIV accelerates aging or acts as an additive risk factor remains uncertain.
  • In SMART, fully adjusted mortality odds ratios (fourth vs first quartile) were 8.0 for sCD14, 12.4 for IL-6, and 41.2 for D-dimer; D-dimer showed an IQR of approximately 40, and CRP had an IQR odds ratio of 3.1. The VACS Index predicts all-cause mortality better than an index restricted to HIV-1 RNA, CD4 count, and age, and correlates with IL-6, D-dimer, and sCD14.
  • Psychosocial concerns include limited social networks, stigma, isolation, and mental health problems; depression is reported as high as 50% and anxiety as high as 20% in older adults with HIV, with research priorities spanning prevention, comorbidity management, successful aging, cognition, substance use, caregiving, community resources, and women aging with HIV.

Methods

  • Design: The NIH Office of AIDS Research commissioned a working group/white paper; the group met face-to-face in April 2011 and assigned breakout groups to four areas: triggers/mechanisms of aging in HIV, biomarkers/prognostic indices, design of observational and intervention studies, and societal/mental health/behavioral/caregiving issues.
  • Data or sample: No primary sample or systematic review is described; the report synthesizes cited literature and existing cohorts/trials, including SMART, MACS, WIHS, VACS, FRAM, ESPRIT, ADNI, ASPREE, and SPRINT.
  • Analysis: Narrative expert consensus summary of current knowledge, knowledge gaps, priority research areas, and resource needs; no formal quantitative analysis is reported.

Limitations

  • Stated in the paper: only a small amount of research exists in HIV and aging; it is uncertain whether HIV accelerates aging or is an additive risk factor; animal models cannot reproduce the complexity of HIV, ART, aging, social context, multimorbidity, and functional outcomes; many biomarkers’ causal roles and clinical use are unknown; cohorts often lack precise data on alcohol, tobacco, and psychoactive drug use; and the aging HIV population is predominantly middle-aged, so geriatric syndromes may not be fully appreciated until older thresholds are reached.
  • Evident from the text: as a consensus white paper, it does not use a systematic search, formal evidence grading, or primary data analysis, so its recommendations reflect expert opinion and may not be empirically validated.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1097/qai.0b013e31825a3668

Cites

81 of 81 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 98 cited sources checked · 0 supported · 0 flagged

  • Findingnone given

    These biomarkers were correlated with non-AIDS events observed in the SMART study.

    “These biomarkers were correlated with non-AIDS events observed in the SMART study.”
    Quote in the paperSubstantial claim
  • Findingcitation

    Few middle aged individuals with HIV infection demonstrate the full frailty phenotype.

    “While few middle aged individuals with HIV infection demonstrate the full frailty phenotype (66), there is a concern that those with HIV infection may have significantly decreased physiologic reserve at younger ages than those without HIV infection.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [66] Desquilbet L Jacobson LP Fried LP Phair JP Jamieson BD Holloway M Margolick JB HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty J Gerontol A Biol Sci Med Sci 2007 62 1279 86 18000149 source

      Not checked in the free run.

  • Findingcitation

    After adjusting for the VACS Index, IL-6 does not substantially improve the discrimination of all cause mortality.

    “After adjusting for the VACS Index, IL-6 does not substantially improve the discrimination of all cause mortality (61).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Justice AC Freiberg MS Tracy R Tate J Goetz M Butt AA Rodriguez-Barradas M Gibert C Oursler KA Bryant KJ Does an Index Composed of Clinical Data Reflect Effects of Inflammation, Coagulation, and Monocyte Activation on Mortality Among those Aging with HIV? Clin Infect Dis 2012 In Press PMC3297653 22337823

      Not checked in the free run.

  • Findingcitation

    The addition of D-dimer or sCD14 to the VACS Index results in improved risk classification.

    “While the VACS Index predicts all cause mortality more accurately than D-dimer or sCD14, the addition of either marker results in improved risk classification.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Justice AC Freiberg MS Tracy R Tate J Goetz M Butt AA Rodriguez-Barradas M Gibert C Oursler KA Bryant KJ Does an Index Composed of Clinical Data Reflect Effects of Inflammation, Coagulation, and Monocyte Activation on Mortality Among those Aging with HIV? Clin Infect Dis 2012 In Press PMC3297653 22337823

      Not checked in the free run.

  • Findingcitation

    The VACS Index predicts all cause mortality more accurately than D-dimer or sCD14.

    “While the VACS Index predicts all cause mortality more accurately than D-dimer or sCD14, the addition of either marker results in improved risk classification.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Justice AC Freiberg MS Tracy R Tate J Goetz M Butt AA Rodriguez-Barradas M Gibert C Oursler KA Bryant KJ Does an Index Composed of Clinical Data Reflect Effects of Inflammation, Coagulation, and Monocyte Activation on Mortality Among those Aging with HIV? Clin Infect Dis 2012 In Press PMC3297653 22337823

      Not checked in the free run.

  • May combine two claims. 20
  • Classified as probably not a substantial claim. 15

  • May combine two claims.

    Findingnone given

    In SMART, D-dimer showed a remarkable ability to predict future mortality with an IQR of approximately 40.

    “In SMART D-dimer showed a remarkable ability to predict future mortality with an IQR of approximately 40.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    In SMART, both CRP and SAP were measured, but only CRP predicted mortality in SMART.

    “In SMART, both CRP and SAP were measured (since both predict CVD and mortality in the elderly), but only CRP predicted mortality in SMART.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Biomarkers of chronic inflammation and hypercoagulability such as IL-6, sCD14, and D-dimer are elevated among those with HIV infection compared with demographically matched uninfected controls and are higher still among HIV-infected individuals with unsuppressed levels of HIV-1 RNA.

    “Biomarkers of chronic inflammation and hypercoagulability such as IL-6, sCD14, and D-dimer are elevated among those with HIV infection compared with demographically matched uninfected controls and are higher still among HIV-infected individuals with unsuppressed levels of HIV-1 RNA (70,71).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [70] Kuller LH Tracy R Belloso W De WS Drummond F Lane HC Ledergerber B Lundgren J Neuhaus J Nixon D Inflammatory and coagulation biomarkers and mortality in patients with HIV infection PLoS Med 2008 5 10 e203 18942885 PMC2570418

      Not checked in the free run.

    • cites [71] Neuhaus J Jacobs DR Jr Baker JV Calmy A Duprez D La RA Kuller LH Pett SL Ristola M Ross MJ Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection J Infect Dis 2010 201 1788 95 20446848 PMC2872049

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationreasoning

    The hazard ratios and stability of D-dimer are remarkable and unique to HIV disease.

    “The hazard ratios and stability of D-dimer are remarkable and unique to HIV disease.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based). May combine two claims.

    Interpretationnone given

    Compression of disease development and functional decline in HIV-infected individuals offers a unique model of multi-morbidity that should be applicable to many populations.

    “Compression of disease development and functional decline in HIV-infected individuals offers a unique model of multi-morbidity that should be applicable to many populations (e.g. the aged, dialysis patients, chronic inflammatory conditions such as rheumatoid arthritis).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    SAP is possibly more affected by the suppression of liver protein synthesis in HIV disease than CRP was.

    “SAP is also produced predominantly by the liver, and possibly more affected by the suppression of liver protein synthesis in HIV disease than CRP was.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Aging HIV-infected persons exhibit an excess burden of co-morbid conditions and the premature onset of clinical symptoms and syndromes often associated with advanced aging, multi-morbidity, poly-pharmacy, limited reserve, and functional decline.

    “As a result, aging HIV-infected persons exhibit an excess burden of co-morbid conditions and the premature onset of a number of clinical symptoms and syndromes that are often associated with advanced aging, multi-morbidity, poly-pharmacy, limited reserve and functional (physical and cognitive) decline (Figure 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    HIV-associated, Non-AIDS (HANA) conditions include cardiovascular disease, a number of infectious and noninfectious cancers, osteopenia/osteoporosis, liver disease, renal disease, and neurocognitive decline.

    “These include cardiovascular disease (6), a number of infectious and noninfectious cancers (7,8), osteopenia/osteoporosis (9), liver disease (10), renal disease (11,12) and neurocognitive decline.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [6] Freiberg MS McGinnis K Butt AA Goetz M Brown S Oursler KA Rodriguez-Barradas M Gibert C Rimland D Justice AC HIV is associated with clinically confirmed myocardial infarction after adjustment for smoking and other risk factors 18th Conference on Retroviruses and Opportunistic Infections 2011 Abs. 809

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [7] Silverberg MJ Chao C Leyden WA Xu L Tang B Horberg MA Klein D Quesenberry CP Jr Towner WJ Abrams DI HIV infection and the risk of cancers with and without a known infectious cause AIDS 2009 23 2337 45 19741479 PMC2863991 source

      Not checked in the free run.

    • cites [8] Silverberg MJ Lau B Jing Y D’Souza G Engels EA Gill J Goedert JJ Kirk GD Justice AC Dubrow R Risk of anal cancer in HIV-infected patients and HIV-infected controls in North America 12th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies 2010 Abs. 306

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [9] Womack JA Goulet JL Gibert C Brandt C Chang CC Gulanski B Fraenkel L Mattocks K Rimland D Rodriguez-Barradas MC Increased risk of fragility fractures among HIV infected compared to uninfected male veterans PLoS One 2011 6 e17217 21359191 PMC3040233 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the SMART studies, the fully adjusted odds ratios of mortality (fourth versus first quartile) in HIV disease were 8.0, 12.4, and 41.2 for sCD14, IL-6, and D-dimer, respectively, and these odds ratios are higher than those observed in the general population.

    “For example, in the SMART studies, the fully adjusted odds ratios of mortality (fourth versus first quartile; IQR) in HIV disease were 8.0, 12.4, and 41.2 for sCD14, IL-6 and D-dimer, respectively (47); these odds ratios are higher than those observed in the general population.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47] Kuller LH Tracy R Belloso W Inflammatory and coagulation biomarkers and mortality in patients with HIV infection PLoS Med 2008 5 e203 18942885 PMC2570418 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The mechanisms accounting for the excess risk of HANA conditions in long-term treated HIV-infected adults likely include persistent immune dysfunction/inflammation, treatment toxicity, co-infections such as CMV, HCV, and HBV, and traditional risk factors including use of alcohol, tobacco, and psychoactive drugs.

    “The mechanisms accounting for this excess risk likely include persistent immune dysfunction/inflammation, treatment toxicity, co-infections such as CMV, HCV and hepatitis B virus (HBV) and traditional risk factors (including use of alcohol, tobacco, and psychoactive drugs) (15,47,48).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [15] Effros RB Fletcher CV Gebo K Aging and infectious diseases: workshop on HIV infection and aging: What is known and future research directions Clin Inf Dis 2008 47 542 53 PMC3130308 18627268 source

      Not checked in the free run.

    • cites [47] Kuller LH Tracy R Belloso W Inflammatory and coagulation biomarkers and mortality in patients with HIV infection PLoS Med 2008 5 e203 18942885 PMC2570418 source

      Not checked in the free run.

    • cites [48] Deeks SG HIV Infection, Inflammation, Immunosenescence, and Aging Annu Rev Med 2011 62 141 55 21090961 PMC3759035 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a combined analysis from WIHS and MACS, the initiation of effective antiretroviral therapy was associated with the expected decline in IL-6 and D-dimer, but an apparent increase in CRP.

    “In a combined analysis from WIHS and MACS, the initiation of effective antiretroviral therapy was associated with the expected decline in IL-6 and D-dimer, but an apparent increase in CRP (49).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] Palella FJ Jr Gange SJ Benning L Inflammatory biomarkers and abacavir use in the Women’s Interagency HIV Study and the Multicenter AIDS Cohort Study AIDS 2010 24 1657 65 20588104 PMC3514460

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Numerous aspects of immune and cellular senescence have been documented in the elderly, but only a few of them have been extended to studies in HIV-infected individuals.

    “There are numerous aspects of immune and cellular senescence that have been documented in the elderly but only a few of them have been extended to studies in HIV-infected individuals (31,32).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [31] Akbar AN Soares MV Plunkett FJ Salmon M Differential regulation of CD8+ T cell senescence in mice and men Mech Ageing Dev 2000 121 69 76 11164461 source

      Not checked in the free run.

    • cites [32] Appay V Rowland-Jones S Premature ageing of the immune system: the cause of AIDS? Trends Immunol 2002 23 580 585 12464569 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    Integration of clinical measures, common laboratory values, and emerging biomarkers is likely to be more robust than relying on simple, traditional, HIV-specific variables such as CD4 count or viral load.

    “Integration of clinical measures, common laboratory values and emerging biomarkers is likely to be more robust than relying on simple, traditional, HIV-specific variables such as CD4 count or viral load.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    The lack of animal models that can appropriately reproduce the complexities of HIV, ART, aging, social context, multi-morbidity, and functional outcomes of relevance indicates that human studies should be the primary focus of research in this area.

    “the lack of animal models that can appropriately reproduce complexities of HIV, ART, aging, social context, multi-morbidity and functional outcomes of relevance indicate that human studies should be the primary focus of research in this area.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationreasoning

    The Geriatric concepts of multi-morbidity, personalized care, maximizing function, and deriving integrated management strategies are very likely relevant to the care of the growing middle to older age adult population with HIV.

    “The Geriatric concepts of multi-morbidity, personalized care, maximizing function, and deriving integrated management strategies are, however, very likely relevant to the care of the growing middle to older age adult population with HIV.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Issues regarding HIV in aging people are a high priority area among a large and diverse community of advocacy groups active in the area of HIV.

    “Further, as outlined in the White House Conference (16), issues regarding HIV in aging people is a high priority area among a large and diverse community of advocacy groups active in the area of HIV.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] http://www.whitehouse.gov/blog/2011/09/16/national-hivaids-and-aging-awareness-day-perspective-national-institutes-health

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    There is evidence of age-associated defects in TLR-induced production of IL-6 and TNF-alpha, particularly in response to engagement of TLR1/2, as well as a generalized defect in TLR-induced CD80 upregulation in monocytes from older individuals.

    “There is evidence of age-associated defects in TLR-induced production of IL-6 and TNF-alpha, particularly in response to engagement of TLR1/2, as well as a generalized defect in TLR-induced CD80 upregulation in monocytes from older individuals (45).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Shaw AC Panda A Joshi SR Dysregulation of human Toll-like receptor function in aging Ageing Res Rev 2011 10 346 53 21074638 PMC3633557

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    There is a concern that those with HIV infection may have significantly decreased physiologic reserve at younger ages than those without HIV infection.

    “While few middle aged individuals with HIV infection demonstrate the full frailty phenotype (66), there is a concern that those with HIV infection may have significantly decreased physiologic reserve at younger ages than those without HIV infection.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Faith-based organizations may have resources to meet needs of older adults with HIV but are likely underutilized due to stigma and lack of understanding of service needs.

    “Furthermore, some community-based resources, such as faith-based organizations, may have resources to meet the needs of older adults with HIV, but are likely underutilized due to stigma issues as well as a lack of understanding of the service needs of these older adults (78).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [78] Vance DE Brennan M Enah C Smith GL Kaur J Religion, spirituality, and older adults with HIV: Critical personal and social resources for an aging epidemic Clinical Interventions in Aging 2011 6 101 109 21753865 PMC3131980

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    FIB 4 is associated with risk of all cause mortality and strongly predictive of incident hepatocellular cancer.

    “FIB 4 is also clearly associated with risk of all cause mortality and strongly predictive of incident hepatocellular cancer (53, 57).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [53] Cook NR Assessing the Incremental Role of Novel and Emerging Risk Factors Curr Cardiovasc Risk Rep 2010 4 112 9 20640227 PMC2904250

      Not checked in the free run.

    • cites [57] Park LS Tate JP Justice AC Lo RV III Lim JK Brau N Brown ST Butt AA Gibert C Goetz MB FIB-4 Index Is Associated with Hepatocellular Carcinoma Risk in HIV-Infected Patients Cancer Epidemiol Biomarkers Prev 2011 20 2512 7 22028407 PMC3237927

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The Framingham index predicts cardiovascular events, but its thresholds may vary from HIV-uninfected populations and may under-estimate risk.

    “While it predicts cardiovascular events, the thresholds may vary from HIV-uninfected populations and may under-estimate risk and HIV-specific indices (e.g., DAD CV index) that may be more accurate (62–64)”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [62] Edwards-Jackson N Kerr S Tieu H Cardiovascular risk assessment in persons with HIV infection in the developing world comparing three risk equations in a cohort of HIV-infected Thais HIV Med 2011 12 510 5 21375686

      Not checked in the free run.

    • cites [63] Barros ZM de Alencar Ximenes RA Miranda-Filho DB Comparison between the Framingham and prospective cardiovascular of Munster scores for assessment of coronary heart disease in human immunodeficiency virus positive patients in Brazil Metab Syndr Relat Disord 2010 8 489 97 20973693

      Not checked in the free run.

    • cites [64] Friis-mooler N Thiebaut R Reiss P Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse events of anti-HIV drugs study Eur J Cardiovasc Prev Rehabil 2010 17 491 501 20543702

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The geriatric literature has called into question the wisdom of following all applicable primary and secondary prevention guidelines among those with multi-morbidity, polypharmacy, and reduced life expectancy.

    “The geriatric literature has called into question the wisdom of following all applicable primary and secondary prevention guidelines among those with multi-morbidity, polypharmacy, and reduced life expectancy (74).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [74] Akgun KM Pisani MA Fried TR Butt AA Gibert CL McGinnis K Huang L Rimland D Justice AC Rodriguez-Barradas MC Risk Factors for Medical Intensive Care Unit Admission in HIV Infected Veterans American Thoracic Society 2010

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Frailty is a syndrome characterized in HIV-uninfected adults, typically in their 7th, 8th, or 9th decade, by muscle weakness, weight loss, fatigue, and low levels of physical activity signifying a decreased ability to withstand further injury.

    “Frailty is a syndrome characterized in HIV-uninfected adults, typically in their 7th, 8th, or 9th decade, by muscle weakness, weight loss, fatigue, and low levels of physical activity signifying a decreased ability to withstand further injury (65).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [65] Walston J Hadley EC Ferrucci L Guralnik JM Newman AB Studenski SA Ershler WB Harris T Fried LP 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 16776798 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    These arguments likely apply to those aging with HIV infection.

    “These arguments likely apply to those aging with HIV infection.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    HANA conditions include cardiovascular disease, infectious and noninfectious cancers, osteopenia/osteoporosis, liver cirrhosis, and renal disease.

    “These include cardiovascular disease, a number of infectious and noninfectious cancers (7,8), osteopenia/osteoporosis(9), liver cirrhosis (10), and renal disease (11, 12).”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [7] Silverberg MJ Chao C Leyden WA Xu L Tang B Horberg MA Klein D Quesenberry CP Jr Towner WJ Abrams DI HIV infection and the risk of cancers with and without a known infectious cause AIDS 2009 23 2337 45 19741479 PMC2863991 source

      Not checked in the free run.

    • cites [8] Silverberg MJ Lau B Jing Y D’Souza G Engels EA Gill J Goedert JJ Kirk GD Justice AC Dubrow R Risk of anal cancer in HIV-infected patients and HIV-infected controls in North America 12th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies 2010 Abs. 306

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [9] Womack JA Goulet JL Gibert C Brandt C Chang CC Gulanski B Fraenkel L Mattocks K Rimland D Rodriguez-Barradas MC Increased risk of fragility fractures among HIV infected compared to uninfected male veterans PLoS One 2011 6 e17217 21359191 PMC3040233 source

      Not checked in the free run.

    • cites [10] Sulkowski MS Thomas DL Hepatitis C in the HIV-Infected Person Ann Intern Med 2003 138 197 207 12558359 source

      Not checked in the free run.

    • cites [11] Lucas GM Mehta SH Atta MG Kirk GD Galai N Vlahov D Moore RD End-stage renal disease and chronic kidney disease in a cohort of African-American HIV-infected and at-risk HIV-seronegative participants followed between 1988 and 2004 AIDS 2007 21 2435 43 18025880 source

      Not checked in the free run.

    • cites [12] Fischer MJ Wyatt CM Gordon K Gibert C Brown ST Rimland D Rodriguez-Barradas M Justice AC Parikh CR and the VACS Project Team Hepatitis C is associated with a high prevalence of chronic kidney disease and mortality among veterans with HIV HSR&D National Meeting 2009 Abs 3026

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Deriving sense from past experience may be especially important for older women compared to younger women who more often look ahead to the future.

    “Being able to derive some sense from their many years of past experience may be especially important compared to its importance for younger women who more often are looking ahead to the future.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Substance use has played a critical role in the HIV epidemic through direct transmission behaviors and by increasing risky sexual behaviors.

    “Substance use has played a critical role in the HIV epidemic, through direct transmission behaviors (e.g., sharing injection drug use equipment) and through the influence of substance use (drugs and alcohol) on increasing risky sexual behaviors (89).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [89] Green TC Kershaw T Lin H Heimer R Goulet JL Kraemer KL Gordon AJ Maisto SA Day NL Bryant K Patterns of drug use and abuse among aging adults with and without HIV: A latent class analysis of a US Veteran cohort Drug Alcohol Depend 2010 110 208 20 20395074 PMC3087206

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    Older adults with HIV are likely to experience service barriers when attempting to engage community-based providers.

    “However, they are likely to experience service barriers when attempting to engage community-based providers.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    There may be several causes for cognitive declines in older adults with HIV, such as increased depression and anxiety, more social isolation, poverty, substance use, not being employed, inflammation, and co-morbidities.

    “however, there may be several causes for such declines such as increased depression and anxiety, more social isolation, poverty, substance use, not being employed, inflammation, co-morbidities, etc. (85).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [85] Fazeli PL Marceaux JC Vance DE Slater L Long CA Predictors of cognition in adults with HIV: Implications for nursing practice and research Journal of Neuroscience Nursing 2011 43 36 50 21338043 PMC3039887

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Meaning making may be an especially important coping strategy for older women because of their developmental life stage.

    “Further, “meaning making” may be an especially important coping strategy for older women because of their developmental life stage.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    HIV affects people from a variety of social and ethnic backgrounds, some of whom have more competencies and resources to cope with the disease.

    “Additionally, HIV affects those from a variety of social and ethnic backgrounds, some who have more competencies and resources to cope with the disease (79).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [79] Vance DE Struzick TC Masten J Hardiness, successful aging, and HIV:Implications for social work Journal of Gerontological Social Work 2008 51 260 283 19042651

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationreasoning

    This has major implications for targeting HIV prevention messages for this population historically excluded in HIV prevention campaigns.

    “This has major implications for targeting HIV prevention messages for this population historically excluded in HIV prevention campaigns.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Many women over 50 remain sexually active but do not appreciate their HIV disease risk because contraceptive choice no longer plays a role in sexual decision making.

  • May combine two claims.

    Premisecitation

    Depression is as high as 50 percent and anxiety as high as 20 percent in older adults with HIV.

    “some studies show that depression is as high at 50 percent and anxiety as high as 20 percent in older adults with HIV (81).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [81] Vance DE Mugavero M Willig J Raper JL Saag MS Aging with HIV: A cross-sectional study of co-morbidity prevalenceclinical characteristics across decades of life J Assoc Nurses AIDS Care 2011 22 17 25 20471864

      Not checked in the free run.

33 of 33

  • The paper relies on this without support.

    HIV risk behaviors, susceptibility to HIV acquisition, progression of disease after infection, and response to anti-retroviral therapy all vary by age.

    “HIV risk behaviors, susceptibility to HIV acquisition, progression of disease after infection, and response to anti-retroviral therapy all vary by age.”

  • The paper relies on this without support.

    Current effective treatment has increased the median life expectancy to more than 70 years of age in those living with HIV.

    “In those living with HIV, current effective treatment has increased the median life expectancy to > 70 years of age.”

  • The paper relies on this without support.

    There has been only a small amount of research in the field of HIV and aging.

    “Biologic, medical, individual social and societal issues change as one ages with HIV infection, but there has been only a small amount of research in this field.”

  • The paper relies on this without support.

    The development and application of effective antiretroviral therapy for HIV has allowed many infected persons to live to an older age.

    “The development and application of effective antiretroviral therapy (ART) for HIV has allowed many infected persons to live to an older age.”

  • The paper relies on this without support.

    By 2015, half the people living with HIV infection in the United States will be 50 years of age or over.

    “Thus, by 2015, half the people living with HIV infection in the United States will be 50 years of age or over.”

  • The paper relies on this without support.

    People with HIV infection are more likely to be co-infected with chronic viruses such as hepatitis C.

    “People with HIV infection are also more likely to be co-infected with chronic viruses such as hepatitis C, which interacts with HIV or with alcohol use to lead to more rapid cirrhosis and more rapid development of hepatocellular carcinoma.”

  • The paper relies on this without support.

    Hepatitis C interacts with HIV or with alcohol use to lead to more rapid cirrhosis and more rapid development of hepatocellular carcinoma.

    “People with HIV infection are also more likely to be co-infected with chronic viruses such as hepatitis C, which interacts with HIV or with alcohol use to lead to more rapid cirrhosis and more rapid development of hepatocellular carcinoma.”

  • The paper relies on this without support.

    People with HIV infection differentially represent sexual and racial minorities with constrained economic and social resources.

    “People with HIV infection differentially represent sexual and racial minorities with constrained economic and social resources.”

  • The paper relies on this without support.

    Issues of homelessness, food insecurity, and social isolation may exacerbate substance use and complicate the aging process broadly—physically, emotionally, and socially.

    “As a result, issues of homelessness, food insecurity, and social isolation may exacerbate substance use and complicate the aging process broadly – physically, emotionally, and socially.”

  • The paper relies on this without support.

    At the moment, the population aging with HIV infection is predominantly middle aged.

    “At the moment, the population aging with HIV infection is predominantly middle aged.”

  • The paper relies on this without support.

    Many geriatric syndromes of greatest concern in the general population, including dementia, frailty, and falls, are not common among those under 65 years of age and are frequently seen only in those 80+ years of age.

    “Many geriatric syndromes of greatest concern in the general population, including dementia, frailty, and falls, are not common among those under 65 years of age and are frequently seen only in those 80+ years of age.”

  • The paper relies on this without support.

    Aging with HIV infection is typically characterized by the development of multiple chronic diseases and treatments.

    “Aging with HIV infection is typically characterized by the development of multiple chronic diseases and treatments.”

  • The paper relies on this without support.

    In those aging with HIV, it is nearly impossible to separate HIV, treatment effects, aging, and disease.

    “In those aging with HIV, it is nearly impossible to separate these factors.”

  • The paper relies on this without support.

    Immune senescence, inflammation, and hypercoagulability appear to be unifying mechanisms that may lead to the greater incidence of disease in persons aging with HIV.

    “Immune senescence, inflammation and hypercoagulability – These appear to be unifying mechanisms that may lead to the greater incidence of disease in persons aging with HIV, and should be a focus for future research drawing on the substantial database already available from HIV-uninfected cohorts.”

  • The paper relies on this without support.

    More than 50 percent of individuals affected by HIV in the United States will be age 50 years or greater by 2015.

    “the working group members believe the issues outlined here are high priority as more than 50 percent of individuals affected by HIV in the U.S will be age 50 years or greater by 2015.”

  • The paper relies on this without support.

    Proactive prevention of geriatric syndromes is preferred to interventions aimed to reverse diseases which have already occurred.

    “A common theme from the geriatric literature is that proactive prevention of geriatric syndromes is preferred to interventions aimed to reverse diseases which have already occurred;”

  • The paper relies on this without support.

    Human aging is associated with substantial changes in both the innate and adaptive immune response at the phenotypic, functional, and molecular levels.

    “Human aging is associated with substantial changes in both the innate and adaptive immune response and occur at the phenotypic, functional, and molecular levels.”

  • The paper relies on this without support.

    Immune changes that occur during normal aging may occur earlier in chronically HIV-1 infected individuals.

    “It is now recognized that immune changes that occur during normal aging may occur earlier in chronically HIV-1 infected individuals.”

  • The paper relies on this without support.

    There may be synergistic effects of aging and HIV in chronically HIV-1 infected individuals resulting in complex pathologies and precipitous immune decline.

    “There also may be synergistic effects of aging and HIV in this population resulting in complex pathologies and precipitous immune decline.”

  • The paper relies on this without support.

    Most studies on aging and HIV have utilized peripheral blood, which contains approximately 2 percent of the host immune cells.

    “Most studies on aging and HIV have utilized peripheral blood which contains approximately 2 percent of the host immune cells.”

  • The paper relies on this without support.

    Cellular senescence is an important mechanism that contributes to organismal aging.

    “Cellular senescence is an important mechanism that contributes to organismal aging.”

  • The paper relies on this without support.

    Shortening of telomeric sequences and structural changes to the telomere are believed to be major drivers of the senescence program in all individuals.

    “Shortening of telomeric sequences and structural changes to the telomere are believed to be major drivers of the senescence program in all individuals.”

  • The paper relies on this without support.

    Telomere length decreases with age in all hematopoietic lineages that have been studied, including circulating CD38 hematopoietic precursor cells, neutrophils, and naïve and memory T cells.

    “Telomere length decreases with age in all hematopoietic lineages that have been studied, including circulating CD38 hematopoietic precursor cells, neutrophils, and naïve and memory T cells.”

  • The paper relies on this without support.

    HIV-infected individuals demonstrate features of immunologic aging including accumulation of terminal stage, effector CD8+ T cells with shortened telomeres, absence of telomerase activity, and limited T cell proliferation potential.

    “Emerging data from a number of groups suggest that HIV-infected individuals demonstrate features of immunologic aging including accumulation of terminal stage, effector CD8+ T cells (most often identified by the absence of CD28 expression) with shortened telomeres, absence of telomerase activity, and limited T cell proliferation potential.”

  • The paper relies on this without support.

    The presence of terminal stage effector CD8+ T cells has been associated with clinical problems in seniors including reduced vaccine responses, bone loss, neurocognitive decline, and cardiovascular disease.

    “The biologic consequence for the accumulation of these cells is controversial, but their presence has been associated with clinical problems in seniors including reduced vaccine responses, bone loss, neurocognitive decline and cardiovascular disease.”

  • The paper relies on this without support.

    The immunology of aging is thought to be influenced by other chronic viral pathogens, particularly cytomegalovirus (CMV).

    “It is also important to note that the immunology of aging is thought to be influenced by other chronic viral pathogens, particularly cytomegalovirus (CMV).”

  • The paper relies on this without support.

    CMV infection is characterized by the oligoclonal expansion of a CMV specific T cell population that comprises a large fraction of the T cell repertoire.

    “CMV infection is characterized by the oligoclonal expansion of a CMV specific T cell population that comprises a large fraction of the T cell repertoire.”

  • The paper relies on this without support.

    Age-associated T cell changes include an increase in the number of regulatory T cells both within the CD4 and CD8 subsets, a generalized chronic inflammatory state, a shift in the balance of Th1, Th2, Th17, and T-regulatory responses, and alterations in cells of the innate immune system.

    “Specifically, age-associated T cell changes include an increase in the number of regulatory T cells both within the CD4 and CD8 subsets, and a generalized chronic inflammatory state (which may reflect the combined effects of senescent T cell cytokine secretion), a shift in the balance of Th1, Th2, Th17, and T-regulatory responses, and alterations in cells of the innate immune system.”

  • The paper relies on this without support.

    Inflammaging is associated with frailty and increased mortality risk in the very old, HIV-uninfected population.

    “This so-called “inflammaging” is associated with frailty and increased mortality risk in the very old, HIV-uninfected population.”

  • The paper relies on this without support.

    Humoral immunity is affected by aging, as evidenced by the dramatic decline in antibody responses to a variety of vaccines and markedly increased risk of pathogens typically controlled by antibody-based mechanisms.

    “Humoral immunity is affected by aging as well, as evidenced by the dramatic decline in antibody responses to a variety of vaccines and markedly increased risk of pathogens typically controlled by antibody-based mechanisms (e.g. Streptococcus pneumoniae).”

  • The paper relies on this without support.

    Major intrinsic B cell defects include a reduction in both somatic hypermutation of the immunoglobulin genes and in class switching, which contribute to the blunted titer and affinity of antibodies in the elderly.

    “The major intrinsic B cell defects include a reduction in both somatic hypermutation of the immunoglobulin genes and in class switching, which undoubtedly contribute to the blunted titer and affinity of antibodies in the elderly.”

  • The paper relies on this without support.

    Aging is associated with diminished numbers and sizes of the lymph node germinal centers, which may impact affinity maturation and antibody quality, as well as a reduction in the number of B cells migrating out of the bone marrow.

    “Aging is also associated with diminished numbers and sizes of the lymph node germinal centers, which may impact affinity maturation and antibody quality, as well as a reduction in the number of B cells migrating out of the bone marrow.”

  • The paper relies on this without support.

    Proinflammatory cytokine production by cells of the monocyte/macrophage lineage is hypothesized to be influenced by the complex interplay of immunologic, hormonal, and neuroendocrine factors.

    “The proinflammatory cytokine production by cells of the monocyte/macrophage lineage is hypothesized to be influenced by the complex interplay of immunologic, hormonal, and neuroendocrine factors.”

  • The paper relies on this without support.

    Circulating levels of adipokines and adrenal hormones are altered during aging.

    “Circulating levels of adipokines and adrenal hormones are altered during aging.”

  • The paper relies on this without support.

    Natural killer (NK) cells show defects in cytotoxicity and signal transduction, and natural killer T (NKT) cells have some overlapping phenotypic features with senescent CD8 T cells.

    “Other cell types within the innate immune system that undergo age-related changes include natural killer (NK) cells, which show defects in cytotoxicity and signal transduction, and natural killer T (NKT) cells, which have some overlapping phenotypic features with senescent CD8 T cells.”

  • The paper relies on this without support.

    Diminished neutrophil function accompanies aging (e.g., reduced phagocytic capacity and intracellular killing) and is clinically manifested by high morbidity and mortality due to bacterial infections.

    “Diminished neutrophil function that accompanies aging (e.g. reduced phagocytic capacity and intracellular killing) clinically manifested by high morbidity and mortality due to bacterial infections is another area worthy of more extensive research.”

  • The paper relies on this without support.

    In rheumatoid arthritis, lymphocytes display a phenotype consistent with accelerated immune aging including accelerated telomere attrition, accumulation of differentiated effector T cell populations that have lost the CD28 marker, and contraction in T cell receptor repertoire diversity.

    “In rheumatoid arthritis, lymphocytes display a phenotype consistent with accelerated immune aging including accelerated telomere attrition, accumulation of differentiated effector T cell populations that have lost the CD28 marker and contraction in T cell receptor repertoire diversity.”

  • The paper relies on this without support.

    Compared to normal age-matched controls, T lymphocytes from patients with rheumatoid arthritis have increased numbers of DNA double-strand breaks and increased spontaneous apoptosis rates; repair of radiation-induced DNA breaks is reduced and delayed.

    “Compared to normal age-matched controls, T lymphocytes from patients with rheumatoid arthritis have increased numbers of DNA double-strand breaks and increased spontaneous apoptosis rates; repair of radiation-induced DNA breaks is reduced and delayed.”

  • The paper relies on this without support.

    Although combination antiretroviral therapy is highly effective in suppressing HIV replication, it does not fully restore health.

    “Although combination antiretroviral therapy is highly effective in suppressing HIV replication, it does not fully restore health.”

  • The paper relies on this without support.

    Many studies of biomarkers reported to date have included untreated and treated individuals, despite the fact that HIV replication is known to be a major determinant of inflammation, immune function, and overall health.

    “Many studies of biomarkers reported to date have included untreated and treated individuals, despite the fact that HIV replication is known to be major a determinant of inflammation, immune function and overall health.”

  • The paper relies on this without support.

    Even those studies that focused on long-term treated individuals rarely controlled for the degree of viral suppression.

    “Even those studies that focused on long-term treated individuals rarely controlled for the degree of viral suppression.”

  • The paper relies on this without support.

    Use of alcohol, tobacco, and psychoactive drugs affects both biomarker behavior and the risk of non-AIDS morbidity and mortality; the lack of precise data regarding these factors in most cohorts prevents a careful assessment regarding mechanisms.

    “Further, use of alcohol, tobacco, and psychoactive drugs affects both biomarker behavior and the risk of non-AIDS morbidity and mortality; the lack of precise data regarding these factors in most cohorts prevents a careful assessment regarding mechanisms.”

  • The paper relies on this without support.

    HIV infection results in chronic activation/dysfunction of the innate and adaptive immune responses, leading to inflammation and perhaps the development of most non-AIDS conditions.

    “HIV infection results in chronic activation/dysfunction of the innate and adaptive immune responses, leading to inflammation and perhaps the development of most non-AIDS conditions.”

  • The paper relies on this without support.

    HIV infection also causes a loss of effective immune surveillance, which may contribute to cancer and other complications.

    “HIV infection also causes a loss of effective immune surveillance, which may contribute to cancer and other complications.”

  • The paper relies on this without support.

    Many putative HIV-associated biomarkers have established prognostic significance in HIV-uninfected populations.

    “Many putative HIV-associated biomarkers have established prognostic significance in HIV-uninfected populations.”

  • The paper relies on this without support.

    The interaction between certain biomarkers appears to be different in HIV-infected and HIV-uninfected individuals.

    “The interaction between certain biomarkers appears to be different in HIV-infected and HIV-uninfected infected individuals.”

  • The paper relies on this without support.

    There is accumulating evidence that the behavior of certain biomarkers in the context of treated HIV disease is different from that in the general population.

    “There is accumulating evidence that the behavior of certain biomarkers in the context of treated HIV disease is different from that in general population.”

  • The paper relies on this without support.

    The association between these biomarkers and subsequent morbidity/mortality appears to be stronger in those with HIV infection compared to HIV-uninfected individuals.

    “The association between these biomarkers and subsequent morbidity/mortality appears to be stronger in those with HIV infection compared HIV-uninfected individuals.”

  • The paper relies on this without support.

    The durability in terms of prognostic significance of certain biomarkers also appears to be unique among HIV-infected adults.

    “The durability in terms of prognostic significance of certain biomarkers also appears to be unique among HIV-infected adults.”

  • The paper relies on this without support.

    The stability in terms of prognosis of high plasma D-dimer is years longer than that which has been observed in the general population.

    “This stability in terms of prognosis is years longer than that which has been observed in the general population.”

  • The paper relies on this without support.

    IL-6 levels are strongly associated with near-term mortality in the elderly in general, and with mortality among well-controlled HIV seropositive individuals.

    “IL-6 levels are strongly associated with near-term mortality in the elderly in general, and with mortality among well-controlled HIV seropositive individuals.”

  • The paper relies on this without support.

    D-dimer predicts venous thrombosis at all ages.

    “D-dimer predicts venous thrombosis at all ages.”

  • The paper relies on this without support.

    D-dimer predicts CVD and mortality in middle-aged and elderly people, more powerfully in the latter.

    “D-dimer also predicts CVD and mortality in middle-aged and elderly people, more powerfully in the latter.”

  • The paper relies on this without support.

    The level of sCD14 in plasma has been strongly associated with mortality independent of other factors, including LPS, in treated HIV disease.

    “The level of sCD14 in plasma has been strongly associated with mortality independent of other factors (including LPS) in treated HIV disease.”

  • The paper relies on this without support.

    The frequency of T cells expressing CD38 and HLA-DR is markedly elevated in untreated HIV infection and associated with mortality independent of HIV RNA levels and CD4+ T cell counts.

    “The frequency of T cells expressing CD38 (which is a cell surface ectoenzyme involved in regulating cell activation) and HLA-DR (Major Histocompatibility Complex (MHC) class II receptor) is markedly elevated in untreated HIV infection and associated with mortality independent of HIV RNA levels and CD4+ T cell counts.”

  • The paper relies on this without support.

    The frequency of these actively turning over cells declines with ART but often fails to normalize.

    “The frequency of these actively turning over cells declines with ART but often fails to normalize.”

  • The paper relies on this without support.

    A higher frequency of senescent T cells, including those that are CD28− and/or CD57+, has been associated with cardiovascular disease in HIV-infected adults.

    “A higher frequency of these cells — including those that are CD28− and/or CD57+ — has been associated with cardiovascular disease in HIV-infected adults”

  • The paper relies on this without support.

    A higher frequency of senescent T cells is believed to be causally associated with morbidity in very old HIV-uninfected individuals.

    “and is believed to be causally associated with morbidity in very old HIV-uninfected individuals.”

  • The paper relies on this without support.

    Due largely to the advances of antiretroviral therapy, in industrialized countries HIV has been transformed into a manageable, chronic condition leading to the emergence of a large population aging with this disease.

    “Due largely to the advances of antiretroviral therapy (ART), in industrialized countries HIV has been transformed into a manageable, chronic condition leading to the emergence of a large population aging with this disease.”

  • The paper relies on this without support.

    There is substantial excess risk of myocardial infarction among those with HIV infection compared with demographically similar uninfected controls.

    “Given the substantial excess risk of myocardial infarction among those with HIV infection compared with demographically similar uninfected controls”

  • The paper relies on this without support.

    An increasing number of women with HIV will now live through the menopausal transition and beyond.

    “An increasing number of women with HIV will now live through the menopausal transition and beyond.”

  • The paper relies on this without support.

    Long term HIV infection and its treatment may increase risk for the same co-morbidities associated with reproductive aging.

    “With emerging evidence that long term HIV infection and its treatment may increase risk for the same co-morbidities associated with reproductive aging”

  • The paper relies on this without support.

    HIV Associated Non-AIDS conditions are increasingly common and associated with aging and chronic inflammation.

    “HIV Associated Non-AIDS (HANA) conditions are increasingly common and associated with aging and chronic inflammation.”

  • The paper relies on this without support.

    Chronic inflammation and hypercoagulability occur when the body is exposed to chronic antigen stimulation through a number of possible mechanisms including chronic viral infection and microbial translocation.

    “Chronic inflammation and hypercoagulability occur when the body is exposed to chronic antigen stimulation through a number of possible mechanisms including chronic viral infection and microbial translocation.”

  • The paper relies on this without support.

    Chronic inflammation is thought to play an important role in many diseases of aging including cardiovascular and rheumatologic diseases.

    “It is thought to play an important role in many diseases of aging including cardiovascular and rheumatologic diseases.”

  • The paper relies on this without support.

    Those aging with HIV have many reasons to have chronic antigen stimulation including infection with HIV and common co-infection with HCV, HBV, HPV, and CMV; microbial translocation from HIV and from alcohol; and oxidative stress from smoking, obesity, and ART toxicity.

    “As noted in the prior section, those aging with HIV have many reasons to have chronic antigen stimulation including infection with HIV and common co-infection with HCV, HBV, HPV, and CMV; microbial translocation from HIV (72) and from alcohol (73), and oxidative stress from smoking, obesity, and ART toxicity.”

  • The paper relies on this without support.

    Outcomes of primary interest remain morbidity, mortality, and cost.

    “Outcomes of primary interest remain morbidity, mortality, and cost.”

  • The paper relies on this without support.

    The concept of personalized care rests on the observation that those at greatest risk of a particular disease often reap the largest benefit from screening and prevention, thereby justifying the risks and/or costs associated with the intervention.

    “The concept of personalized care rests on the observation that those at greatest risk of a particular disease often reap the largest benefit from screening and prevention thereby justifying the risks and/or costs associated with the intervention (screening test or preventative therapy).”

  • The paper relies on this without support.

    The wisdom of combining behavioral and therapeutic approaches has already been demonstrated in the treatment of depression, alcohol addiction, and smoking cessation.

    “The wisdom of combining behavioral and therapeutic approaches has already been demonstrated in the treatment of depression, alcohol addiction, and smoking cessation.”

  • The paper relies on this without support.

    Older adults with HIV face considerable psychosocial challenges with regard to social engagement, informal social supports, caregiving resources, and utilization of community-based services.

    “Likewise, the burgeoning population of older adults with HIV also faces considerable psychosocial challenges with regard to social engagement and interaction, adequacy of informal social supports and care giving resources, and utilization of community-based services to meet their growing needs.”

  • The paper relies on this without support.

    Truncated social networks in older adults with HIV result from HIV-stigma, social isolation due to rejection, and self-protective withdrawal.

    “These truncated social networks result from a variety of reasons, including HIV-stigma and resultant social isolation due to rejection from social network members, as well as self-protective withdrawal.”

  • The paper relies on this without support.

    Social network insufficiency in older adults with HIV may be attributed to histories of incarceration and use of alcohol, tobacco, and psychoactive drugs.

    “Social network insufficiency may also be attributed to histories of incarceration and use of alcohol, tobacco, and psychoactive drugs.”

  • The paper relies on this without support.

    Social isolation in older adults with HIV is linked to high levels of loneliness and depression and insufficiency of instrumental and emotional support from family and friends.

    “Such isolation has been linked to high levels of loneliness and depression and insufficiency of instrumental and emotional support from both family and friends.”

  • The paper relies on this without support.

    Aging is a complex process physically, mentally, and socially that takes place within societal infrastructures, and this complexity increases with HIV disease.

    “Aging is a complex process physically, mentally, and socially which takes place within societal infrastructures such as the medical community; this complexity increases with HIV disease.”

  • The paper relies on this without support.

    Those who have aged with HIV are often very different from those who contracted HIV in later life.

    “Those who have aged with HIV are often very different from those who have contracted HIV in later life.”

  • The authors state this as an assumption.

    It is uncertain what older adults know about HIV and safer sex, and little is known about barriers to practicing safer sex among those who have knowledge.

    “It is uncertain what older adults know about HIV and safer sex. In addition, for those who have the knowledge, little is known about the barriers to practicing safer sex.”

  • The paper relies on this without support.

    Vulnerability to HIV in older adults is complicated by poorer cognitive functioning, health disparities, depression, mental illness, and substance use.

    “This vulnerability is further complicated in many normal older adults by poorer cognitive functioning, health disparities, depression, mental illness, and substance use.”

  • The paper relies on this without support.

    Many women over 50 remain sexually active but do not appreciate their HIV disease risk because contraceptive choice no longer plays a role in sexual decision making.

    “Many women over 50 remain sexually active but do not appreciate their HIV disease risk as contraceptive choice no longer plays a role in sexual decision making.”

  • The authors state this as an assumption.

    How older adults with HIV integrate information about HIV with information about other co-morbidities is not well understood.

    “How older adults with HIV do so is not well understood, especially in view of cognitive problems, depression, polypharmacy, substance use, and other complications (82).”

  • The paper relies on this without support.

    Other mental health issues such as bipolar disorder, schizophrenia, and substance use contribute to and exacerbate everyday functioning, medical management, and sexual decision making.

    “Other mental health issues such as bipolar disorder, schizophrenia, and substance use contribute to and exacerbate everyday functioning, medical management, and sexual decision making.”

  • The paper relies on this without support.

    Stigma remains a powerful factor for those living with HIV, including older adults.

    “Meanwhile, stigma remains a powerful factor for those living with HIV, including those who are older.”

  • The paper relies on this without support.

    Women with or at risk for HIV infection are a particularly disempowered group, tending to be poor, African American or Latina, and often having a history of trauma.

    “Women with or at risk for HIV infection are a particularly disempowered group in that they tend to be poor, African American or Latina, and often have a history of trauma.”

  • The paper relies on this without support.

    Traditional gender role norms (prioritizing care for others, silencing self, subordinating to male partners) are associated with poor outcomes in many chronic diseases.

    “Investigating the degree to which women identify with traditional gender role norms, such as prioritizing care for others over self- care, silencing the needs of the self to avoid relational conflict and loss, and subordinating themselves to male partners has been associated with poor outcomes in many chronic diseases.”

  • The paper relies on this without support.

    Women utilizing active coping strategies (seeking education, persistence, meaning making) have better quality of life and health outcomes.

    “Also, women utilizing active coping strategies, such as seeking education, being persistent, and making meaning (i.e. the act of “making sense” of an experience) have been shown to have better quality of life and health outcomes.”

  • The paper relies on this without support.

    The quality of women's relationships with sexual partners, family members, and providers affects how they contract and cope with HIV and adhere to HIV treatment.

    “Understanding internalized gender roles and their relationships to coping strategies is particularly important because the quality of women’s relationships with their sexual partners, family members and providers affects how they contract and cope with HIV and adhere to HIV treatment.”

  • The paper relies on this without support.

    The demands of aging may mean self-care becomes more important for maintaining quality of life at older ages than at younger ages.

    “The demands of the aging process may mean self-care may become even more important in maintaining quality of life at older ages than it is at younger ages.”
86 of 86

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  • Epidemiological data suggests that individuals with various chronic diseases such as cancer, diabetes, and HIV/AIDS are more likely to develop co-morbidities later in life.

    “Epidemiological data does suggest that individuals with various chronic diseases such as cancer, diabetes, and HIV/AIDS are more likely to develop co-morbidities later in life,72,73,74”

    From Asynchronous, contagious and digital aging (2021) · cites this paper as [74]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Guideline discussion cites the ICU-admission reference

    Minor

    The statement about clinical practice guidelines cites reference 74, whose listed title is about risk factors for intensive-care admission. Reference 75 is the listed paper about clinical practice guidelines for patients with multiple comorbidities.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. Kuller, 2008, . Inflammatory and coagulation biomarkers and mortality in patients with HIV infection., PLoS Med, 5, e203, 10.1371/journal.pmed.0050203 · DOI · Paper page
  2. Neuhaus, 2010, . Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection., J Infect Dis, 201, 1788, 10.1086/652749 · DOI · Paper page
  3. Green, 2010, . Patterns of drug use and abuse among aging adults with and without HIV: a latent class analysis of a US Veteran cohort., Drug Alcohol Depend, 110, 208, 10.1016/j.drugalcdep.2010.02.020 · DOI · Paper page

Cited by

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Related

Authors
High, K. P., Brennan-Ing, M., Clifford, D. B., Cohen, M. H., Currier, J., Deeks, S. G., Deren, S., Effros, R. B., Gebo, K., Goronzy, J. J., Justice, A. C., Landay, A., Levin, J., Miotti, P. G., Munk, R. J., Nass, H., Rinaldo, C. R., Shlipak, M. G., Tracy, R., Valcour, V., Vance, D. E., Walston, J. D., & Volberding, P.
Affiliations
  • Atrium Health Wake Forest Baptist (US)
  • Washington University in St. Louis (US)
  • Rush University (US)
  • University of California, Los Angeles (US)
  • University of California, San Francisco (US)
  • New York University (US)
  • Stanford Medicine (US)
  • Rush University Medical Center (US)
  • National Institutes of Health (US)
  • University of Pittsburgh (US)
  • San Francisco VA Medical Center (US)
  • University of Vermont (US)
Corresponding author
  • High, Kevin P.
  • Gebo, Kelly
  • Nass, Heidi
  • Walston, Jeremy D.
ORCID
Venue
JAIDS Journal of Acquired Immune Deficiency Syndromes
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2012-07-01
Volume
60
Issue
Supplement 1
Pages
S1-S18
ISSN
1525-4135 (ISSN-L)
DOI
10.1097/qai.0b013e31825a3668
PMC
PMC3413877
OpenAlex
W1992604744
Semantic Scholar
f57873a233330a95d57a8fa89c9368fed2cdc8c2
Cited by
522
References
81
Citations by year
2026: 14 · 2025: 10 · 2024: 27 · 2023: 20 · 2022: 35 · 2021: 28 · 2020: 43 · 2019: 43 · 2018: 47 · 2017: 49 · 2016: 52 · 2015: 39 · 2014: 62 · 2013: 48 · 2012: 4
FWCI
54.43
Type
journal article
Language
en
Open access
Locations
  • JAIDS Journal of Acquired Immune Deficiency Syndromes (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (U13AG040938, P30AG021332)
  • National Institute of Allergy and Infectious Diseases (P30AI027763)
Topics
  • Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
Keywords
HIV, aging, older adults, multimorbidity, polypharmacy, immunosenescence, inflammation, hypercoagulability, antiretroviral therapy, functional capacity, HIV disease progression, HIV risk behavior, research agenda, community support, caregivers, long-term cohort follow-up
MeSH terms
Aged, Aging, Health Services Needs and Demand, Health Services Research, Humans, Middle Aged, Biomarkers, HIV Infections, Comorbidity, Polypharmacy, Anti-HIV Agents, Needs Assessment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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