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1. Do people living with HIV experience greater age advancement than their HIV-negative counterparts?

Author

De Francesco, Davide, Wit, Ferdinand W., Burkle, Alexander, Oehlke, Sebastian, Kootstra, Neeltje A., Winston, Alan, Franceschi, Claudio, Garagnani, Paolo, Pirazzini, Chiara, Libert, Claude, Grune, Tilman, Weber, Daniela, Jansen, Eugene H. J. M., Sabin, Caroline A., Reiss, Peter, Reiss, P., Winston, A., Wit, F. W., Prins, M., van der Loeff, M. F. Schim, Schouten, J., Schmand, B., Geurtsen, G. J., Sharp, D. J., Caan, M. W. A., Majoie, C., Villaudy, J., Berkhout, B., Kootstra, N. A., Gisslen, M., Pasternak, A., Sabin, C. A., Guaraldi, G., Burkle, A., Libert, C., Franceschi, C., Kalsbeek, A., Fliers, E., Hoeijmakers, J., Pothof, J., van der Valk, M., Bisschop, P. H., Portegies, P., Zaheri, S., Burger, D., Cole, J. H., Biirkle, A., Zikkenheiner, W., Janssen, F. R., Underwood, J., Kooij, K. W., van Zoest, R. A., Doyle, N., van der Loeff, M. Schim, Schmand, B. A., Verheij, E., Verboeket, S. O., Elsenga, B. C., Hillebregt, M. M. J., Ruijs, Y. M. C., Benschop, D. P., Tembo, L., McDonald, L., Stott, M., Legg, K., Lovell, A., Erlwein, O., Kingsley, C., Norsworthy, P., Mullaney, S., Kruijer, T., del Grande, L., Olthof, V, Visser, G. R., May, L., Verbraak, F., Demirkaya, N., Visser, I, Majoie, C. B. L. M., Su, T., Leech, R., Huguet, J., Frankin, E., van der Kuyl, A., Weijer, K., Siteur-Van Rijnstra, E., Harskamp-Holwerda, A. M., Maurer, I, Ruiz, M. M. Mangas, Girigorie, A. F., Boeser-Nunnink, B., Kals-Beek, A., Bisschop, P. H. L. T., de Graaff-Teulen, M., Dewaele, S., Garagnani, P., Pirazzini, C., Capri, M., Dall'Olio, F., Chiricolo, M., Salvioli, S., Fuchs, D., Zetterberg, H., Weber, D., Grune, T., Jansen, E. H. J. M., De Francesco, D., Sindlinger, T., Oehlke, S., Global Health, AII - Infectious diseases, APH - Aging & Later Life, Experimental Immunology, ANS - Neurodegeneration, AMS - Restoration & Development, Medical Psychology, and APH - Mental Health

Subjects
Male, 0301 basic medicine, CYTOMEGALOVIRUS, HIV Infections, DISEASE, 0302 clinical medicine, Biomarkers of aging, Medicine and Health Sciences, Immunology and Allergy, 030212 general & internal medicine, the Co-morBidity in Relation to AIDS (COBRA) Collaboration, POPULATION, Immunodeficiency, education.field_of_study, premature aging, virus diseases, 11 Medical And Health Sciences, Middle Aged, Hepatitis B, SOUTH-AFRICA, Infectious Diseases, Anti-Retroviral Agents, Cohort, Female, Life Sciences & Biomedicine, medicine.drug, Adult, Premature aging, medicine.medical_specialty, BIOMARKERS, Immunology, Population, biomarkers of aging, 17 Psychology And Cognitive Sciences, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Virology, ddc:570, Internal medicine, medicine, Humans, accelerated aging, education, Aged, accelerated aging, aging, biological age, biomarkers of aging, HIV, premature aging, Science & Technology, business.industry, aging, Biology and Life Sciences, HIV, 06 Biological Sciences, medicine.disease, COMORBIDITIES, biological age, INFECTED INDIVIDUALS, IMMUNOGLOBULIN-G ANTIBODY, PROTEASE INHIBITORS, Cross-Sectional Studies, 030104 developmental biology, RISK-FACTORS, business, Saquinavir
Abstract

Objectives: Despite successful antiretroviral (ARV) therapy, people living with HIV (PLWH) may show signs of premature/accentuated aging. We compared established biomarkers of aging in PLWH, appropriately-chosen HIV-negative individuals, and blood donors, and explored factors associated with biological age advancement.Design: Cross-sectional analysis of 134 PLWH on suppressive ARV therapy, 79 lifestyle-comparable HIV-negative controls aged ≥45 years from the Co-morBidity in Relation to AIDS (COBRA) cohort, and 35 age-matched blood donors (BD).Methods: Biological age was estimated using a validated algorithm based on ten biomarkers. Associations between ‘age advancement’ (biological minus chronological age) and HIV status/parameters, lifestyle, cytomegalovirus (CMV), hepatitis B (HBV) and hepatitis C virus (HCV) infections were investigated using linear regression.Results: The average (95% CI) age advancement was greater in both HIV-positive [13.2 (11.6, 14.9) years] and HIV-negative [5.5 (3.8, 7.2) years] COBRA participants compared to BD [-7.0 (-4.1, -9.9) years, both p's < 0.001)], but also in HIV-positive compared to HIV-negative participants (p < 0.001). Chronic HBV, higher anti-CMV IgG titer and CD8+ T-cell count were each associated with increased age advancement, independently of HIV-status/group. Among HIV-positive participants, age advancement was increased by 3.5 (0.1, 6.8) years among those with nadir CD4+ < 200 cells/μL and by 0.1 (0.06, 0.2) years for each additional month of exposure to saquinavir.Conclusions: Both treated PLWH and lifestyle-comparable HIV-negative individuals show signs of age advancement compared to BD, to which persistent CMV, HBV co-infection and CD8+ T-cell activation may have contributed. Age advancement remained greatest in PLWH and was related to prior immunodeficiency and cumulative saquinavir exposure. published

Published
2019
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2. Impact of comorbidity and ageing on health-related quality of life in HIV-positive and HIV-negative individuals

Author

Langebeek, Nienke, Kooij, Katherine W., Wit, Ferdinand W., Stolte, Ineke G., Sprangers, Mirjam A.G., Reiss, Peter, Nieuwkerk, Pythia T., Van Der Valk, M., Schouten, J., Van Zoest, R. A., Verheij, E., Verboeket, S. O., Elsenga, B. C., Prins, M., Van Der Loeff, M. F.Schim, Berkel, J., Totté, M., Kruijer, T., Del Grande, L., Gambier, C., Visser, G. R., May, L., Kovalev, S., Newsum, A., Dijkstra, M., Zaheri, S., Hillebregt, M. M.J., Ruijs, Y. M.C., Benschop, D. P., El Berkaoui, A., Zikkenheiner, W., Janssen, F. R., Kootstra, N. A., Harskamp-Holwerda, A. M., Maurer, I., Booiman, T., Mangas Ruiz, M. M., Girigorie, A. F., Boeser-Nunnink, B., Geerlings, S. E., Godfried, M. H., Goorhuis, A., Van Vugt, M., De Jong, J., Lips, P., De Jong, M., Verbraak, F. D., Schadé, A., Mulder, W. M.C., Anatomy and neurosciences, Medical psychology, Internal medicine, Surgery, APH - Aging & Later Life, Pediatric surgery, Ophthalmology, Psychiatry, APH - Health Behaviors & Chronic Diseases, Other departments, AII - Infectious diseases, APH - Mental Health, Medical Psychology, CCA -Cancer Center Amsterdam, Global Health, AII - Amsterdam institute for Infection and Immunity, and APH - Personalized Medicine

Subjects
Male, 0301 basic medicine, Gerontology, Aging, Immunology, Population, HIV Infections, Comorbidity, 03 medical and health sciences, 0302 clinical medicine, Quality of life, mental disorders, Humans, Immunology and Allergy, Medicine, Prospective Studies, 030212 general & internal medicine, education, Prospective cohort study, Depression (differential diagnoses), Aged, education.field_of_study, Depression, business.industry, virus diseases, Middle Aged, medicine.disease, 030112 virology, humanities, Patient Health Questionnaire, Infectious Diseases, Cohort, Quality of Life, Female, business, Cohort study
Abstract

Background: HIV-infected individuals may be at risk for the premature onset of age-associated noncommunicable comorbidities. Being HIV-positive, having comorbidities and being of higher age may adversely impact health-related quality of life (HRQL). We investigated the possible contribution of HIV infection, comorbidities and age on HRQL and depression. Methods: HIV-infected individuals and uninfected controls from the AGEhIV Cohort Study were screened for the presence of comorbidities. They completed the Short Form 36-item Health Survey to assess HRQL and the nine-item Patient Health Questionnaire to assess depression. Linear and logistic regression were used to investigate to which extent comorbidities, aging and HIV infection were independently associated with HRQL and depression. Results: HIV-infected individuals (n = 541) reported significantly worse physical and mental HRQL and had a higher prevalence of depression than HIV-uninfected individuals (n = 526). A higher number of comorbidities and HIV-positive status were each independently associated with worse physical HRQL, whereas HIV-positive status and younger age were independently associated with worse mental HRQL and more depression. The difference in physical HRQL between HIV-positive and HIV-negative individuals did not become greater with a higher number of comorbidities or with higher age. Conclusion: In a cohort of largely well suppressed HIV-positive participants and HIV-negative controls, HIV-positive status was significantly and independently associated with worse physical and mental HRQL and with an increased likelihood of depression. Our finding that a higher number of comorbidities was independently associated with worse physical HRQL reinforces the importance to optimize prevention and management of comorbidities as the HIV-infected population continues to age.

Published
2017
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3. High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid

Author

Booiman, Thijs, Wit, Ferdinand W., Maurer, Irma, De Francesco, Davide, Sabin, Caroline A., Harskamp, Agnes M., Prins, Maria, Garagnani, Paolo, Pirazzini, Chiara, Franceschi, Claudio, Fuchs, Dietmar, Gisslén, Magnus, Winston, Alan, Reiss, Peter, Kootstra, Neeltje A., Reiss, P., Wit, F. W. N. M., Schouten, J., Kooij, K. W., van Zoest, R. A., Elsenga, B. C., Janssen, F. R., Heidenrijk, M., Zikkenheiner, W., van der Valk, M., Kootstra, N. A., Booiman, T., Harskamp-Holwerda, A. M., Boeser-Nunnink, B., Maurer, I., Mangas Ruiz, M. M., Girigorie, A. F., Villaudy, J., Frankin, E., Pasternak, A., Berkhout, B., van der Kuyl, T., Portegies, P., Schmand, B. A., Geurtsen, G. J., ter Stege, J. A., Klein Twennaar, M., Majoie, C. B. L. M., Caan, M. W. A., Su, T., Weijer, K., Bisschop, P. H. L. T., Kalsbeek, A., Wezel, M., Visser, I., Ruhé, H. G., Franceschi, C., Garagnani, P., Pirazzini, C., Capri, M., Dall’Olio, F., Chiricolo, M., Salvioli, S., Hoeijmakers, J., Pothof, J., Prins, M., Martens, M., Moll, S., Berkel, J., Totté, M., Kovalev, S., Gisslén, M., Fuchs, D., Zetterberg, H., Winston, A., Underwood, J., McDonald, L., Stott, M., Legg, K., Lovell, A., Erlwein, O., Doyle, N., Kingsley, C., Sharp, D. J., Leech, R., Cole, J. H., Zaheri, S., Hillebregt, M. M. J., Ruijs, Y. M. C., Benschop, D. P., Burger, D., de Graaff-Teulen, M., Guaraldi, G., Bürkle, A., Sindlinger, T., Moreno-Villanueva, M., Keller, A., Sabin, C., de Francesco, D., Libert, C., Dewaele, S., Booiman, Thij, Wit, Ferdinand W., Maurer, Irma, De Francesco, Davide, Sabin, Caroline A., Harskamp, Agnes M., Prins, Maria, Garagnani, Paolo, Pirazzini, Chiara, Franceschi, Claudio, Fuchs, Dietmar, Gisslã©n, Magnu, Winston, Alan, Reiss, Peter, Kootstra, Neeltje A., Schouten, J., Kooij, K. W., van Zoest, R. A., Elsenga, B. C., Janssen, F. R., Heidenrijk, M., Zikkenheiner, W., van der Valk, M., Kootstra, N. A., Harskamp-Holwerda, A. M., Boeser-Nunnink, B., Mangas Ruiz, M. M., Girigorie, A. F., Villaudy, J., Frankin, E., Pasternak, A., Berkhout, B., van der Kuyl, T., Portegies, P., Schmand, B. A., Geurtsen, G. J., ter Stege, J. A., Klein Twennaar, M., Majoie, C. B. L. M., Caan, M. W. A., Su, T., Weijer, K., Bisschop, P. H. L. T., Kalsbeek, A., Wezel, M., Visser, I., Ruhã©, H. G., Capri, M., Dall'Olio, F., Chiricolo, M., Salvioli, S., Hoeijmakers, J., Pothof, J., Martens, M., Moll, S., Berkel, J., Tottã©, M., Kovalev, S., Zetterberg, H., Underwood, J., Mcdonald, L., Stott, M., Legg, K., Lovell, A., Erlwein, O., Doyle, N., Kingsley, C., Sharp, D. J., Leech, R., Cole, J. H., Zaheri, S., Hillebregt, M. M. J., Ruijs, Y. M. C., Benschop, D. P., Burger, D., de Graaff-Teulen, M., Guaraldi, G., Bã¼rkle, A., Sindlinger, T., Moreno-Villanueva, M., Keller, A., de Francesco, D., Libert, C., Dewaele, S., National Institute for Health Research, ANS - Neuroinfection & -inflammation, Other departments, Infectious diseases, APH - Aging & Later Life, AII - Infectious diseases, Global Health, Experimental Immunology, AII - Amsterdam institute for Infection and Immunity, APH - Global Health, Graduate School, Medical Microbiology and Infection Prevention, Medical Psychology, AMS - Amsterdam Movement Sciences, APH - Mental Health, Radiology and Nuclear Medicine, ACS - Amsterdam Cardiovascular Sciences, Cell Biology and Histology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, Endocrinology Laboratory, ACS - Microcirculation, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, and Netherlands Institute for Neuroscience (NIN)

Subjects
0301 basic medicine, monocyte, COAGULATION, Viremia, Inflammation, CSF, CD38, Monocyte, immune activation, DISEASE, 03 medical and health sciences, INNATE IMMUNE ACTIVATION, MARKERS, Medicine and Health Sciences, Major Article, medicine, Journal Article, CD64, CD40, Immune activation, biology, business.industry, HIV, Biology and Life Sciences, CHRONIC HIV-INFECTION, medicine.disease, 3. Good health, CHEMOATTRACTANT PROTEIN-1, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, Oncology, inflammation, Immunology, Cohort, RISK-FACTORS, biology.protein, HEMOGLOBIN SCAVENGER RECEPTOR, GUT EPITHELIAL BARRIER, CD163, Neurology (clinical), medicine.symptom, business
Abstract

Background Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). Methods A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation, intestinal damage, and inflammation in plasma and cerebrospinal fluid (CSF) of PLHIV with suppressed plasma viremia on combination antiretroviral therapy and age and demographically comparable HIV-negative individuals participating in the Comorbidity in Relation to AIDS (COBRA) cohort and, where appropriate, age-matched blood bank donors (BBD). Results People living with HIV, HIV-negative individuals, and BBD had comparable percentages of classical, intermediate, and nonclassical monocytes. Expression of CD163, CD32, CD64, HLA-DR, CD38, CD40, CD86, CD91, CD11c, and CX3CR1 on monocytes did not differ between PLHIV and HIV-negative individuals, but it differed significantly from BBD. Principal component analysis revealed that 57.5% of PLHIV and 62.5% of HIV-negative individuals had a high monocyte activation profile compared with 2.9% of BBD. Cellular monocyte activation in the COBRA cohort was strongly associated with soluble markers of monocyte activation and inflammation in the CSF. Conclusions People living with HIV and HIV-negative COBRA participants had high levels of cellular monocyte activation compared with age-matched BBD. High monocyte activation was predictive for inflammation in the CSF.

Published
2017
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4. Patterns of Co-occurring Comorbidities in People Living With HIV

Author

De Francesco, Davide, Verboeket, Sebastiaan O, Underwood, Jonathan, Bagkeris, Emmanouil, Wit, Ferdinand W, Mallon, Patrick W G, Winston, Alan, Reiss, Peter, Sabin, Caroline A, Study group members AMC, Reiss, P., Wit, F. W. N. M., Kooij, K. W., van Zoest, R. A., Verheij, E., Verboeket, Sebastiaan O., Prins, M., Kootstra, N. A., Harskamp-Holwerda, A. M., Maurer, Irma, Mangas Ruiz, M. M., Boeser-Nunnink, B. D. M., Geerlings, S. E., Goorhuis, A., Hovius, J. W. R., Nellen, F. J. B., van der Poll, Tom, Prins, J. M., Wiersinga, W. J., van Vugt, M., de Bree, G. J., Postema, P. G., Bisschop, P. H. L. T., Serlie, M. J. M., Dekker, E., van der Velde, N., Willemsen, J. M. R., Vogt, L., Portegies, P., Schmand, B. A., Geurtsen, G. J., Verbraak, F. D., Visser, I., Nieuwkerk, P. T., Majoie, C. B. L. M., Caan, M. W. A., van Lunsen, H. W., van den Born, B. J. H., Stroes, E. S. G., Intensive care medicine, Anatomy and neurosciences, Medical psychology, Internal medicine, APH - Aging & Later Life, Elderly care medicine, Amsterdam Neuroscience - Systems & Network Neuroscience, Ophthalmology, Psychiatry, APH - Mental Health, Radiology and nuclear medicine, ACS - Atherosclerosis & ischemic syndromes, Graduate School, Center of Experimental and Molecular Medicine, Global Health, Infectious diseases, APH - Global Health, Experimental Immunology, APH - Quality of Care, Cardiology, Endocrinology, Gastroenterology and Hepatology, Geriatrics, Nephrology, APH - Health Behaviors & Chronic Diseases, Neurology, Medical Psychology, APH - Societal Participation & Health, Adult Psychiatry, APH - Personalized Medicine, Radiology and Nuclear Medicine, Obstetrics and Gynaecology, Vascular Medicine, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Methodology, ACS - Microcirculation, ACS - Heart failure & arrhythmias, and ACS - Diabetes & metabolism

Subjects
0301 basic medicine, patterns of comorbidities, medicine.medical_specialty, multimorbidity, comorbidities, Major Articles, 03 medical and health sciences, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), Interquartile range, Internal medicine, Health care, medicine, Medical history, 030212 general & internal medicine, Pathological, business.industry, Metabolic disorder, HIV, medicine.disease, 030112 virology, Comorbidity, Mental health, Infectious Diseases, Oncology, Pharmacokinetic and Clinical Observations in PeoPle Over fiftY (POPPY) study and the AGEhIV Cohort Study, business
Abstract

Background The aims of this study were to identify common patterns of comorbidities observed in people living with HIV (PLWH), using a data-driven approach, and evaluate associations between patterns identified. Methods A wide range of comorbidities were assessed in PLWH participating in 2 independent cohorts (POPPY: UK/Ireland; AGEhIV: Netherlands). The presence/absence of each comorbidity was determined using a mix of self-reported medical history, concomitant medications, health care resource use, and laboratory parameters. Principal component analysis (PCA) based on Somers’ D statistic was applied to identify patterns of comorbidities. Results PCA identified 6 patterns among the 1073 POPPY PLWH (85.2% male; median age [interquartile range {IQR}], 52 [47–59] years): cardiovascular diseases (CVDs), sexually transmitted diseases (STDs), mental health problems, cancers, metabolic disorders, chest/other infections. The CVDs pattern was positively associated with cancer (r = .32), metabolic disorder (r = .38), mental health (r = .16), and chest/other infection (r = .17) patterns (all P < .001). The mental health pattern was correlated with all the other patterns (in particular cancers: r = .20; chest/other infections: r = .27; both P < .001). In the 598 AGEhIV PLWH (87.6% male; median age [IQR], 53 [48–59] years), 6 patterns were identified: CVDs, chest/liver, HIV/AIDS events, mental health/neurological problems, STDs, and general health. The general health pattern was correlated with all the other patterns (in particular CVDs: r = .14; chest/liver: r = .15; HIV/AIDS events: r = .31; all P < .001), except STDs (r = –.02; P = .64). Conclusions Comorbidities in PLWH tend to occur in nonrandom patterns, reflecting known pathological mechanisms and shared risk factors, but also suggesting potential previously unknown mechanisms. Their identification may assist in adequately addressing the pathophysiology of increasingly prevalent multimorbidity in PLWH.

Published
2018
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