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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

2. Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment

Author

Underwood, Jonathan, De Francesco, Davide, Cole, James H, Caan, Matthan W A, van Zoest, Rosan A, Schmand, Ben A, Sharp, David J, Sabin, Caroline A, Reiss, Peter, Winston, Alan Coolaboratori: Reiss P, Wit FWNM, Schouten J, Kooij KW, van Zoest RA, Elsenga BC, Janssen FR, Heidenrijk M, Zikkenheiner W, van der Valk M, Kootstra NA, Harskamp-Holwerda AM, Maurer I, Mangas Ruiz MM, Girigorie AF, Villaudy J, Frankin E, Pasternak A, Berkhout B, van der Kuyl T, Portegies P, Schmand BA, Geurtsen GJ, Ter Stege JA, Klein Twennaar M, Majoie CBLM, Caan MWA, Su T, Weijer K, Bisschop PHLT, Kalsbeek A, Wezel M, Visser I, Ruhé HG, 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 DJ, Leech R, Cole JH, Zaheri S, Hillebregt MMJ, Ruijs YMC, Benschop DP, 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, Boffito M, Mallon P, Post F, Sachikonye M, Anderson J, Asboe D, Garvey L, Pozniak A, Vera J, Williams I, Campbell L, Yurdakul S, Okumu S, Pollard L, Otiko D, Phillips L, Laverick R, Fisher M, Clarke A, Bexley A, Richardson C, Macken A, Ghavani-Kia B, Maher J, Byrne M, Flaherty A, Mguni S, Clark R, Nevin-Dolan R, Pelluri S, Johnson M, Ngwu N, Hemat N, Jones M, Carroll A, Whitehouse A, Burgess L, Babalis D, Higgs C, Seah E, Fletcher S, Anthonipillai M, Moyes A, Deats K, Syed I, Matthews C., Underwood, Jonathan, De Francesco, Davide, Cole, James H, Caan, Matthan W A, van Zoest, Rosan A, Schmand, Ben A, Sharp, David J, Sabin, Caroline A, Reiss, Peter, Winston, Alan Coolaboratori: Reiss P, Wit FWNM, Schouten J, Kooij KW, van Zoest RA, Elsenga BC, Janssen FR, Heidenrijk M, Zikkenheiner W, van der Valk M, Kootstra NA, Harskamp-Holwerda AM, Maurer I, Mangas Ruiz MM, Girigorie AF, Villaudy J, Frankin E, Pasternak A, Berkhout B, van der Kuyl T, Portegies P, Schmand BA, Geurtsen GJ, Ter Stege JA, Klein Twennaar M, Majoie CBLM, Caan MWA, Su T, Weijer K, Bisschop PHLT, Kalsbeek A, Wezel M, Visser I, Ruhé HG, 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 DJ, Leech R, Cole JH, Zaheri S, Hillebregt MMJ, Ruijs YMC, Benschop DP, 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, Boffito M, Mallon P, Post F, Sabin C, Sachikonye M, Winston A, Anderson J, Asboe D, Boffito M, Garvey L, Mallon P, Post F, Pozniak A, Sabin C, Sachikonye M, Vera J, Williams I, Winston A, Post F, Campbell L, Yurdakul S, Okumu S, Pollard L, Williams I, Otiko D, Phillips L, Laverick R, Fisher M, Clarke A, Vera J, Bexley A, Richardson C, Mallon P, Macken A, Ghavani-Kia B, Maher J, Byrne M, Flaherty A, Anderson J, Mguni S, Clark R, Nevin-Dolan R, Pelluri S, Johnson M, Ngwu N, Hemat N, Jones M, Carroll A, Whitehouse A, Burgess L, Babalis D, Winston A, Garvey L, Underwood J, Stott M, McDonald L, Boffito M, Asboe D, Pozniak A, Higgs C, Seah E, Fletcher S, Anthonipillai M, Moyes A, Deats K, Syed I, Matthews C., Molecular Genetics, Biomedical Engineering and Physics, Radiology and Nuclear Medicine, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, ACS - Microcirculation, AMS - Restoration & Development, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neurovascular Disorders, Graduate School, AII - Infectious diseases, APH - Aging & Later Life, Medical Psychology, Amsterdam Neuroscience - Neurodegeneration, Global Health, Infectious diseases, APH - Mental Health, APH - Methodology, Commission of the European Communities, Imperial College Healthcare NHS Trust- BRC Funding, and National Institute for Health Research

Subjects
Multivariate statistics, medicine.medical_specialty, COmorBidity in Relation to AIDS (COBRA) Collaboration and the Pharmacokinetic and clinical Observations in PePle over fiftY (POPPY) Study Group, Immunology, Human immunodeficiency virus (HIV), Audiology, medicine.disease_cause, Microbiology, 03 medical and health sciences, 0302 clinical medicine, multivariate, SDG 3 - Good Health and Well-being, Neuroimaging, Medicine and Health Sciences, medicine, Major Article, OLDER-PEOPLE, 030212 general & internal medicine, VALIDITY, Cognitive impairment, cognitive impairment, Science & Technology, neuroimaging, SCORES, business.industry, Biology and Life Sciences, HIV, MEN, Cognition, Mental health, White matter microstructure, PREVALENCE, 3. Good health, Infectious Diseases, Oncology, REGISTRATION, business, Life Sciences & Biomedicine, Neurocognitive, 030217 neurology & neurosurgery
Abstract

Background The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. Methods Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. Results The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05). There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. Conclusion Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach., We have previously described a novel multivariate method (NMM) with theoretical statistical advantages over existing methods, which we assessed here in 3 cohorts of people living with HIV. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status.

Published
2019

3. Structural Brain Abnormalities in Successfully Treated HIV Infection: Associations With Disease and Cerebrospinal Fluid Biomarkers

Author

van Zoest RA, Underwood J, De Francesco D, Sabin CA, Cole JH, Wit FW, Caan MWA, Kootstra NA, Fuchs D, Zetterberg H, Majoie CBLM, Portegies P, Winston A, Sharp DJ, Gisslén M, Reiss P, on behalf of the Comorbidity in Relation to AIDS Collaboration, Franceschi C, Garagnani P, Pirazzini C, Capri M, Dall'Olio F, Chiricolo M, Salvioli S., APH - Aging & Later Life, AII - Infectious diseases, Graduate School, Amsterdam institute for Infection and Immunity, Global Health, Radiology and Nuclear Medicine, Experimental Immunology, Amsterdam Cardiovascular Sciences, Infectious diseases, APH - Global Health, Other departments, Medical Psychology, Amsterdam Movement Sciences, Amsterdam Neuroscience - Neurodegeneration, APH - Mental Health, Medical Microbiology and Infection Prevention, Amsterdam Gastroenterology Endocrinology Metabolism, Laboratory for Endocrinology, Ophthalmology, Other Research, Cell Biology and Histology, APH - Digital Health, APH - Personalized Medicine, APH - Methodology, ACS - Microcirculation, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, van Zoest RA, Underwood, J, De Francesco, D, Sabin, Ca, Cole, Jh, Wit, Fw, Caan, Mwa, Kootstra, Na, Fuchs, D, Zetterberg, H, Majoie, Cblm, Portegies, P, Winston, A, Sharp, Dj, Gisslén, M, Reiss, P, on behalf of the Comorbidity in Relation to AIDS Collaboration,, Franceschi, C, Garagnani, P, Pirazzini, C, Capri, M, Dall'Olio, F, Chiricolo, M, Salvioli, S., Commission of the European Communities, and Imperial College Healthcare NHS Trust- BRC Funding

Subjects
Male, medicine.medical_specialty, Sustained Virologic Response, HIV Infections, Disease, Gastroenterology, Microbiology, cerebrospinal fluid, White matter, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Antiretroviral Therapy, Highly Active, Fractional anisotropy, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, neuroimaging, business.industry, Brain, biomarkers, HIV, 11 Medical And Health Sciences, Middle Aged, 06 Biological Sciences, medicine.disease, Comorbidity, Co-morBidity in Relation to AIDS (COBRA) Collaboration, Infectious Diseases, medicine.anatomical_structure, neurofilament light chain, Anti-Retroviral Agents, Cohort, biomarker, Female, Serostatus, business, 030217 neurology & neurosurgery
Abstract

Background Brain structural abnormalities have been reported in persons living with human immunodeficiency virus (HIV; PLWH) who are receiving suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear. Methods We investigated factors associated with brain tissue volumes and white matter microstructure (fractional anisotropy) in 134 PLWH receiving suppressive cART and 79 comparable HIV-negative controls, aged ≥45 years, from the Comorbidity in Relation to AIDS cohort, using multimodal neuroimaging and cerebrospinal fluid biomarkers. Results Compared with controls, PLWH had lower gray matter volumes (−13.7 mL; 95% confidence interval, −25.1 to −2.2) and fractional anisotropy (−0.0073; 95% confidence interval, −.012 to −.0024), with the largest differences observed in those with prior clinical AIDS. Hypertension and the soluble CD14 concentration in cerebrospinal fluid were associated with lower fractional anisotropy. These associations were independent of HIV serostatus (Pinteraction = .32 and Pinteraction = .59, respectively) and did not explain the greater abnormalities in brain structure in relation to HIV infection. Conclusions The presence of lower gray matter volumes and more white matter microstructural abnormalities in well-treated PLWH partly reflect a combination of historical effects of AIDS, as well as the more general influence of systemic factors, such as hypertension and ongoing neuroinflammation. Additional mechanisms explaining the accentuation of brain structure abnormalities in treated HIV infection remain to be identified.

Published
2018

4. Depression, lifestyle factors and cognitive function in people living with HIV and comparable HIV-negative controls

Author

De Francesco, D., Underwood, J., Bagkeris, E., Boffito, M., Post, F. A., Mallon, P. W. G., Vera, J. H., Williams, I., Anderson, J., Johnson, M., Sabin, C. A., Winston, A., Babalis, Daphne, Boffito, Marta, Burgess, Laura, Mallon, Paddy, Sabin, Caroline, Sachikonye, Memory, Winston, Alan, Asboe, David, Garvey, Lucy, Pozniak, Anton, Clarke, Amanda, Vera, Jaime, Bexley, Andrew, Richardson, Celia, Kirk, Sarah, Gleig, Rebecca, Bracchi, Margherita, Pagani, Nicole, Cerrone, Maddalena, Bradshaw, Daniel, Ferretti, Francesca, Higgs, Chris, Seah, Elisha, Fletcher, Stephen, Anthonipillai, Michelle, Moyes, Ashley, Deats, Katie, Syed, Irtiza, Matthews, Clive, Fernando, Peter, Chiwome, Chido, Hardwick, Shane, Anderson, Jane, Mguni, Sifiso, Clark, Rebecca, Nevin-Dolan, Rhiannon, Pelluri, Sambasivarao, Post, Frank, Campbell, Lucy, Yurdakul, Selin, Okumu, Sara, Pollard, Louise, Santana-Suarez, Beatriz, Macken, Alan, Ghavani-Kia, Bijan, Maher, Joanne, Byrne, Maria, Flaherty, Ailbhe, Babu, Sumesh, Otiko, Damilola, Phillips, Laura, Laverick, Rosanna, Beynon, Michelle, Salz, Anna-Lena, Severn, Abigail, Tembo, Lavender, Stott, Matthew, McDonald, Linda, Dransfield, Felix, Whitehouse, Andrew, Ngwu, Nnenna, Hemat, Nargis, Jones, Martin, Carroll, Anne, Kinloch, Sabine, Youle, Mike, and Madge, Sara

Subjects
0301 basic medicine, Adult, Male, Substance-Related Disorders, HIV Infections, Hashish, RC0109, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cognition, cognitive disorder, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Effects of sleep deprivation on cognitive performance, people living with HIV, Life Style, Depression (differential diagnoses), cognitive function, Aged, Original Research, Depressive Disorder, business.industry, Health Policy, Cognitive disorder, HIV, Middle Aged, medicine.disease, Recreational drug use, 030112 virology, Mental health, Patient Health Questionnaire, Infectious Diseases, Cross-Sectional Studies, HIV‐associated neurocognitive disorders, depression, Female, business, medicine.drug, Demography
Abstract

Objectives\ud We investigated whether differences in cognitive performance between people living with HIV (PLWH) and comparable HIV‐negative people were mediated or moderated by depressive symptoms and lifestyle factors.\ud \ud Methods\ud A cross‐sectional study of 637 ‘older’ PLWH aged ≥ 50 years, 340 ‘younger’ PLWH aged < 50 years and 276 demographically matched HIV‐negative controls aged ≥ 50 years enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study was performed. Cognitive function was assessed using a computerized battery (CogState). Scores were standardized into Z‐scores [mean = 0; standard deviation (SD) = 1] and averaged to obtain a global Z‐score. Depressive symptoms were evaluated via the Patient Health Questionnaire (PHQ‐9). Differences between the three groups and the effects of depression, sociodemographic factors and lifestyle factors on cognitive performance were evaluated using median regression. All analyses accounted for age, gender, ethnicity and level of education.\ud \ud Results\ud After adjustment for sociodemographic factors, older and younger PLWH had poorer overall cognitive scores than older HIV‐negative controls (P < 0.001 and P = 0.006, respectively). Moderate or severe depressive symptoms were more prevalent in both older (27%; P < 0.001) and younger (21%; P < 0.001) PLWH compared with controls (8%). Depressive symptoms (P < 0.001) and use of hashish (P = 0.01) were associated with lower cognitive function; alcohol consumption (P = 0.02) was associated with better cognitive scores. After further adjustment for these factors, the difference between older PLWH and HIV‐negative controls was no longer significant (P = 0.08), while that between younger PLWH and older HIV‐negative controls remained significant (P = 0.01).\ud \ud Conclusions\ud Poorer cognitive performances in PLWH compared with HIV‐negative individuals were, in part, mediated by the greater prevalence of depressive symptoms and recreational drug use reported by PLWH.

Published
2019

5. 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

6. Strategies for preventing group B streptococcal infections in newborns: A nation-wide survey of Italian policies

Author

Tzialla, C, berardi, A, farina, C, clerici, P, borghesi, A, viora, E, scollo, P, stronati, M, Task Force for group B streptococcal infections for the Italian Society of Neonatology including Stival, G, barbaglia, Ma, guala, A, giunta, E, parola, L, grossignani, Mr, perri, P, tubaldi, L, alletto, G, daidone, S, flacco, V, dani, C, sterpa, A, rapisardi, G, elicio, Mr, faldella, G, capretti, Mg, messner, H, bandiera, M, achille, C, azzali, A, montrasio, G, mariani, S, galvagno, G, giacosa, E, de Angelis, F, spandrio, M, serra, A, garofalo, F, perona, A, porcelli, F, ferrero, F, De Franco, S, paollilo, P, picone, S, besana, R, varisco, T, farina, M, memo, L, nicolini, G, lietti, D, Di Chiara, G, rottoli, A, Bonabitacola, T, Cortis, E, Neri, E, Martinelli, S, Ilardi, L, Rondanini, Gf, Calzi, P, Gatta, A, Quntadamo, Pa, Ivaldi, M, Terenzani, L, Di Lascio, N, Travaglio, Md, Vetrano, G, Furcolo, G, Vitacco, V, Intini, C, Frigerio, M, Stroppiana, P, Policicchio, G, Mesirca, P, Gianino, P, Audenio, E, Paludetto, R, Raimondi, F, Pugliese, A, Valentino, L, Nosari, N, Marchesano, G, Chirico, G, Bellù, R, Menchini, M, Poletti, A, E T, Vacchiano, Pinto, L, E D, Perri, Coppola, R, Perini, R, Vetrella, A, De Luca, G, Lista, G, Cavigioli, F, Bettinelli, A, Massironi, E, Franco, C, Bernardo, L, Poli, S, Palladini, M, Tota, V, Spadavecchia, F, Zuccotti, Gv, Pogliani, L, Bracaglia, G, Mancini, Al, Zocco, F, Iozzia, G, Auriemma, A, Teani, M, Mangilli, G, Tempra, Am, Di Terlizi, L, Bottino, R, Salvi, C, Fortunato, V, Musaico, R, Gargantini, G, Carrera, G, Magaldi, R, Taurino, L, D'Onofrio, Am, Buffone, E, Tempera, A, Agosti, M, Garzia, P, Mosca, F, Pugni, L, Tagliabue, P, Colombo, C, Demi, M, Picco, G, Carlucci, A, Zorzi, G, Padula, D, Cardone, Ml, Buonocore, G, Muraca, Mc, Boldrini, A, Ciantelli, M, Lanari, M, Serra, L, Felici, L, Banderalli, G, Brambilla, C, Dall'Agnola, A, Viviani, E, Zonca, Mc, Licardi, G, Chiara, A, Ancora, G, Papa, I, Gancia, P, Pomero, G, Deloglu, A, Villani, P, Mussini, P, Canidio, E, Migliavacca, D, Di Fabio, S, Cipollone, I, Biasucci, G, Rubbi, P, Piepoli, M, Guastaferro, N, Infriccioli, F, Bertino, E, Perathoner, C, Parmigiani, S, Suriano, G, Ianniello, C, Biasini, A, Azzalli, M, Timpani, G, Barresi, S, Caoci, G, Ciccotti, R, De Curtis, M, Natale, F, Finocchi, M, Haass, C, Milillo, F, Lucieri, S, Guercio, E, Canepa, Sa, Scozia, G, Antonucci, R, Limongelli, O, Macciò, S, Mongelli, F, Colonna, F, Dragovic, D, Calipa, Mt, Cohen, A, Moresco, L, Italian Society of Obstetricians and Gynecologists including La Spina, R, Ruggeri, R, Luehwink, A, Brattoli, M, Fedi, A, Lacchi, L, Ettore, G, Pappalardo, E, Conoscenti, G, Zeni, B, Spellecchia, D, Favretti, L, Spagna, L, Zaglio, S, Bresciani, D, Bandini, A, Mancini, R, Mustoni, P, Dodero, D, Grimaldi, M, Di Mario, M, Migliorini, P, Kemeny, A, Anastasio, Ps, Riccardi, T, Maggino, T, Cerri, G, Puggina, P, Marconi, Am, Morgia, S, Bellia, G, D'Anna, Mr, Catania, M, Bacchi Modena, A, Franchi, L, Calonaci, N, Schettini, S, Paradiso, R, Saccucci, P, Ioppi, M, Zorzi, M, Stellin, G, Patacchiola, F, Carrata, L, Bassini, D, San Marco, L, Todros, T, Tibadi, C, Liborio, M, Italian Association of Clinical Microbiologists including Laricchia, R, Tauro, L, Ferrara, F, Nuara, C, Ghiraldi, E, Molinari, F, Comessatti, A, Rocchetti, A, Di Matteo, L, Miconi, V, Calvi, P, Pernigotti, A, Fabozzi, F, Micca, G, Monticone, G, Sarti, M, Da Rin, G, Zoppelletto, M, Modolo, E, Landini, Mp, Furlini, G, Galluppi, E, Pagani, E, Aschbacher, R, Innocenti, P, Bresolin, N, Raggi, Me, Bonfanti, C, De Francesco, M, Santer, P, Griessmaier, A, De Francesco, D, Pirali, A, Prasciolu, C, Usai, F, Cuzzone, G, Scutellà, M, Tramacere, P, Fossati, D, Piaserico, G, Bordignon, G, Sciacca, A, Di Vincenzo, F, Imbriani, A, Melotti, D, Catanoso, G, Rivetti, I, Neri, G, Bruno, R, Bacelle, L, Sartore, P, Giana, G, Sala, E, Giraldi, C, Cavalcanti, P, Perugini, M, Perugini, A, Ginardi, C, Maritano, D, Ferrini, A, Bonettini, A, Avanzini, A, Gasperoni, S, Pieretti, B, Montanari, E, Carillo, C, Rossi, Mr, Laureti, A, Baldoni, Ml, Serra, D, Melioli, G, Bandettini, R, Oneto, F, Colla, R, Storchi Incerti, S, Lanzini, F, Pauri, P, Tili, E, Leone, Ra, Verdastro, G, Megha, M, Luzzaro, F, Conti, A, Busulini, L, Mirri, P, Diodati, R, Vettori, C, Pittalis, S, Anesi, A, Fiore, A, Goglia, L, Vitullo, E, Sinno, A, Platzgummer, S, Spitaler, C, Trabucchi, Mc, Besozzi, M, Cesana, E, Inghilleri, G, Grosso, S, D'Angelo, R, Fogato, E, Lavarda, F, Ortisi, G, Clementi, M, Cichero, P, Rumpianesi, F, Venturelli, C, Mortillaro, F, Daffara, S, Catania, Mr, Iula, D, Andreoni, S, Politi, A, Agostinelli, C, Paparella, C, Capozzi, D, Notaris, P, Bistoni, F, Mencacci, A, Valentini, M, Filippetti, A, Confalonieri, M, Novarese, O, Bonini, F, Salamone, D, Camporese, A, De Rosa, R, Casprini, P, Degl'Innocenti, R, Giordano, R, Allù, Mt, Zanella, D, Malandrino, M, Tronci, M, Valmarin, M, Leonetti, G, Falco, S, Meledandri, M, Ballardini, M, Spanò, A, Cava, Mc, Mascellino, Mt, Schinella, M, Gualdi, P, Casari, E, Scattolo, N, Motta, C, Perfetti, C, Bassano, M, Cera, G, Iafisco, P, Mura, I, Palmieri, A, Migliardi, M, Ferlini, M, Grandi, G, Giardini, F, Albano, F, Latino, M, Ferrero, Mp, Bellizia, L, Russolo, M, Russolo, S, Pesenti, A, Fasano, Ma, Previato, S, Radillo, O, Busetti, M, Ferrari, P, Siderini, V, Puzzolante, L, Scarparo, C, Arzese, A, Cappuccia, N, Lodolo, L, Delledonne, L, Gramoni, A, Maiolo, V, Gheller, A, Spadaro, S, Balzaretti, M, Tzialla, C., Berardi, A., Farina, C., Clerici, P., Borghesi, A., Viora, E., Scollo, P., Stronati, M., Stival, G., Barbaglia, M. A., Guala, A., Giunta, E., Parola, L., Grossignani, M. R., Perri, P., Tubaldi, L., Alletto, G., Daidone, S., Flacco, V., Dani, C., Sterpa, A., Rapisardi, G., Elicio, M. R., Faldella, G., Capretti, M. G., Messner, H., Bandiera, M., Achille, C., Azzali, A., Montrasio, G., Mariani, S., Galvagno, G., Giacosa, E., de Angelis, F., Spandrio, M., Serra, A., Garofalo, F., Perona, A., Porcelli, F., Ferrero, F., De Franco, S., Paollilo, P., Picone, S., Besana, R., Varisco, T., Farina, M., Memo, L., Nicolini, G., Lietti, D., Di Chiara, G., Rottoli, A., Bonabitacola, T., Cortis, E., Neri, E., Martinelli, S., Ilardi, L., Rondanini, G. F., Calzi, P., Gatta, A., Quntadamo, P. A., Ivaldi, M., Terenzani, L., Di Lascio, N., Travaglio, M. D., Vetrano, G., Furcolo, G., Vitacco, V., Intini, C., Frigerio, M., Stroppiana, P., Policicchio, G., Mesirca, P., Gianino, P., Audenio, E., Paludetto, R., Raimondi, F., Pugliese, A., Valentino, L., Nosari, N., Marchesano, G., Chirico, G., Bell(`u), R., Menchini, M., Poletti, A., Vacchiano, T., Pinto, L., Perri, D., Coppola, R., Perini, R., Vetrella, A., De Luca, G., Lista, G., Cavigioli, F., Bettinelli, A., Massironi, E., Franco, C., Bernardo, L., Poli, S., Palladini, M., Tota, V., Spadavecchia, F., Zuccotti, G. V., Pogliani, L., Bracaglia, G., Mancini, A. L., Zocco, F., Iozzia, G., Auriemma, A., Teani, M., Mangilli, G., Tempra, A. M., Di Terlizi, L., Bottino, R., Salvi, C., Fortunato, V., Musaico, R., Gargantini, G., Carrera, G., Magaldi, R., Taurino, L., D?onofrio, A. M., Buffone, E., Tempera, A., Agosti, M., Garzia, P., Mosca, F., Pugni, L., Tagliabue, P., Colombo, C., Demi, M., Picco, G., Carlucci, A., Zorzi, G., Padula, D., Cardone, M. L., Buonocore, G., Muraca, M. C., Boldrini, A., Ciantelli, M., Lanari, M., Serra, L., Felici, L., Banderalli, G., Brambilla, C., Dall?agnola, A., Viviani, E., Zonca, M. C., Licardi, G., Chiara, A., Ancora, G., Papa, I., Gancia, P., Pomero, G., Deloglu, A., Villani, P., Mussini, P., Canidio, E., Migliavacca, D., Di Fabio, S., Cipollone, I., Biasucci, G., Rubbi, P., Piepoli, M., Guastaferro, N., Infriccioli, F., Bertino, E., Perathoner, C., Parmigiani, S., Suriano, G., Ianniello, C., Biasini, A., Azzalli, M., Timpani, G., Barresi, S., Caoci, G., Ciccotti, R., De Curtis, M., Natale, F., Finocchi, M., Haass, C., Milillo, F., Lucieri, S., Guercio, E., Canepa, S. A., Scozia, G., Antonucci, R., Limongelli, O., Macci(`o), S., Mongelli, F., Colonna, F., Dragovic, D., Calipa, M. T., Cohen, A., Moresco, L., La Spina, R., Ruggeri, R., Luehwink, A., Brattoli, M., Fedi, A., Lacchi, L., Ettore, G., Pappalardo, E., Conoscenti, G., Zeni, B., Spellecchia, D., Favretti, L., Spagna, L., Zaglio, S., Bresciani, D., Bandini, A., Mancini, R., Mustoni, P., Dodero, D., Grimaldi, M., Di Mario, M., Migliorini, P., Kemeny, A., Anastasio, P. S., Riccardi, T., Maggino, T., Cerri, G., Puggina, P., Marconi, A. M., Morgia, S., Bellia, G., D?anna, M. R., Catania, M., Bacchi Modena, A., Franchi, L., Calonaci, N., Schettini, S., Paradiso, R., Saccucci, P., Ioppi, M., Zorzi, M., Stellin, G., Patacchiola, F., Carrata, L., Bassini, D., San Marco, L., Todros, T., Tibadi, C., Liborio, M., Laricchia, R., Tauro, L., Ferrara, F., Nuara, C., Ghiraldi, E., Molinari, F., Comessatti, A., Rocchetti, A., Di Matteo, L., Miconi, V., Calvi, P., Pernigotti, A., Fabozzi, F., Micca, G., Monticone, G., Sarti, M., Da Rin, G., Zoppelletto, M., Modolo, E., Landini, M. P., Furlini, G., Galluppi, E., Pagani, E., Aschbacher, R., Innocenti, P., Bresolin, N., Raggi, M. E., Bonfanti, C., De Francesco, M., Santer, P., Griessmaier, A., De Francesco, D., Pirali, A., Prasciolu, C., Usai, F., Cuzzone, G., Scutell(`a), M., Tramacere, P., Fossati, D., Piaserico, G., Bordignon, G., Sciacca, A., Di Vincenzo, F., Imbriani, A., Melotti, D., Catanoso, G., Rivetti, I., Neri, G., Bruno, R., Bacelle, L., Sartore, P., Giana, G., Sala, E., Giraldi, C., Cavalcanti, P., Perugini, M., Perugini, A., Ginardi, C., Maritano, D., Ferrini, A., Bonettini, A., Avanzini, A., Gasperoni, S., Pieretti, B., Montanari, E., Carillo, C., Rossi, M. R., Laureti, A., Baldoni, M. L., Serra, D., Melioli, G., Bandettini, R., Oneto, F., Colla, R., Storchi Incerti, S., Lanzini, F., Pauri, P., Tili, E., Leone, R. A., Verdastro, G., Megha, M., Luzzaro, F., Conti, A., Busulini, L., Mirri, P., Diodati, R., Vettori, C., Pittalis, S., Anesi, A., Fiore, A., Goglia, L., Vitullo, E., Sinno, A., Platzgummer, S., Spitaler, C., Trabucchi, M. C., Besozzi, M., Cesana, E., Inghilleri, G., Grosso, S., D?angelo, R., Fogato, E., Lavarda, F., Ortisi, G., Clementi, M., Cichero, P., Rumpianesi, F., Venturelli, C., Mortillaro, F., Daffara, S., Catania, M. R., Iula, D., Andreoni, S., Politi, A., Agostinelli, C., Paparella, C., Capozzi, D., Notaris, P., Bistoni, F., Mencacci, A., Valentini, M., Filippetti, A., Confalonieri, M., Novarese, O., Bonini, F., Salamone, D., Camporese, A., De Rosa, R., Casprini, P., Degl?innocenti, R., Giordano, R., All(`u), M. T., Zanella, D., Malandrino, M., Tronci, M., Valmarin, M., Leonetti, G., Falco, S., Meledandri, M., Ballardini, M., Span(`o), A., Cava, M. C., Mascellino, M. T., Schinella, M., Gualdi, P., Casari, E., Scattolo, N., Motta, C., Perfetti, C., Bassano, M., Cera, G., Iafisco, P., Mura, I., Palmieri, A., Migliardi, M., Ferlini, M., Grandi, G., Giardini, F., Albano, F., Latino, M., Ferrero, M. P., Bellizia, L., Russolo, M., Russolo, S., Pesenti, A., Fasano, M. A., Previato, S., Radillo, O., Busetti, M., Ferrari, P., Siderini, V., Puzzolante, L., Scarparo, C., Arzese, A., Cappuccia, N., Lodolo, L., Delledonne, L., Gramoni, A., Maiolo, V., Gheller, A., Spadaro, S., Balzaretti, M., Tzialla, Chryssoula, Berardi, Alberto, Farina, Claudio, Clerici, Pierangelo, Borghesi, Alessandro, Viora, Elsa, Scollo, Paolo, Stronati, Mauro, [.., Lanari, Marcello, Faldella, Giacomo, and ]

Subjects
Male, Pediatrics, Group B, 0302 clinical medicine, Neonate, Pregnancy, Surveys and Questionnaires, Prevalence, Mass Screening, Blood culture, 030212 general & internal medicine, Antibiotic prophylaxis, Survey, GBS, Group B streptococcus, Infection, Newborn infant, Adult, Antibiotic Prophylaxis, Female, Health Surveys, Humans, Infant, Newborn, Italy, Neonatal Screening, Pregnancy Complications, Infectious, Prenatal Care, Primary Prevention, Risk Assessment, Streptococcal Infections, Streptococcus agalactiae, reproductive and urinary physiology, Group B streptococcu, medicine.diagnostic_test, lcsh:RJ1-570, Infectious, Perinatology and Child Health, Pediatrics, Perinatology and Child Health, medicine.medical_specialty, Antibiotic sensitivity, Group B Streptococcal Infection, Prenatal care, 03 medical and health sciences, 030225 pediatrics, medicine, Intensive care medicine, Mass screening, business.industry, Public health, Infant, lcsh:Pediatrics, Newborn, Pregnancy Complications, business
Abstract

Background There are no Italian data regarding the strategies for preventing neonatal group B streptococcal (GBS) infection. We conducted a national survey in order to explore obstetrical, neonatal and microbiological practices for the GBS prevention. Methods Three distinct questionnaires were sent to obstetricians, neonatologists and microbiologists. Questionnaires included data on prenatal GBS screening, maternal risk factors, intrapartum antibiotic prophylaxis, microbiological information concerning specimen processing and GBS antimicrobial susceptibility. Results All respondent obstetrical units used the culture-based screening approach to identify women who should receive intrapartum antibiotic prophylaxis, and more than half of the microbiological laboratories (58%) reported using specimen processing consistent with CDC guidelines. Most neonatal units (89 out of 107, 82%) reported using protocols for preventing GBS early-onset sepsis consistent with CDC guidelines. Conclusions The screening-based strategy is largely prevalent in Italy, and most protocols for preventing GBS early-onset sepsis are consistent with CDC guidelines. However, we found discrepancies in practices among centers that may reflect the lack of Italian guidelines issued by public health organizations.

Published
2017

7. Associations between cognitive impairment and patient-reported measures of physical/mental functioning in older people living with HIV

Author

Underwood, J, De Francesco, D, Post, FA, Vera, JH, Williams, I, Boffito, M, Mallon, PW, Anderson, J, Sachikonye, M, Sabin, C, Winston, A, and Pharmacokinetic and Clinical Observations in People Over Fifty (POPPY) study group

Subjects
Gerontology, Male, Activities of daily living, HIV Infections, 03 medical and health sciences, 0302 clinical medicine, Cognition, Acquired immunodeficiency syndrome (AIDS), Surveys and Questionnaires, Virology, Medicine, Dementia, Humans, Pharmacology (medical), Cognitive Dysfunction, 030212 general & internal medicine, Prospective Studies, VALIDITY, Depression (differential diagnoses), Aged, cognitive impairment, Aged, 80 and over, Science & Technology, business.industry, Health Policy, HIV, 1103 Clinical Sciences, Middle Aged, medicine.disease, Mental health, 3. Good health, NEUROPSYCHOLOGICAL IMPAIRMENT, Sexual desire, Infectious Diseases, patient-reported outcomes, Normative, Female, business, activities of daily living, Life Sciences & Biomedicine, 030217 neurology & neurosurgery
Abstract

Objectives: While cognitive impairment is frequently reported in HIV-positive individuals and has historically been associated with poorer functional outcomes, the associations between cognitive impairment and patient-reported outcome measures (PROMs) in contemporary cohorts are unclear.\ud \ud Methods: We tested cognitive function using a computerized battery (CogState™) in 290 HIV-positive and 97 HIV-negative individuals aged ≥ 50 years participating in the Pharmacokinetic and Clinical Observations in People Over Fifty (POPPY) study. Participants completed questionnaires detailing physical and mental health [Short Form Health Survey (SF-36)], cognitive function [European AIDS Clinical Society (EACS) questions], activities of daily living [Lawton Instrumental Activities of Daily Living (IADL)], depression [Patient Depression Questionnaire (PHQ-9) and Centres for Epidemiologic Studies Depression scale (CES-D)], falls and sexual desire. Cognitive impairment was defined using the Frascati criteria, global deficit score (GDS) and multivariate normative comparison (MNC). In the HIV-positive group, the classification performances of the different definitions of cognitive impairment and dichotomized questionnaire results were calculated.\ud \ud Results: The prevalence of cognitive impairment in the HIV-positive group was 34.5% (GDS), 30.0% (Frascati) and 22.1% (MNC), with only 2% diagnosed with HIV-associated dementia. In general, the associations between cognitive impairment and PROMs were weak regardless of the definition used: mean c-statistics were 0.543 (GDS), 0.530 (MNC) and 0.519 (Frascati). Associations were similar using the global T-score to define cognitive impairment. Summary health scores (SF-36) were lower, but only significantly so for those with cognitive impairment identified using MNC, for both mental health (61.4 vs. 75.8; P = 0.03) and physical health (60.9 vs. 75.0; P = 0.03).\ud \ud Conclusions: The associations between cognitive impairment and PROMs were weak, possibly because impairment was mild and therefore largely asymptomatic. Further work is needed to elucidate the clinical implications of cognitive impairment in HIV-disease.

Published
2016

8. Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell- associated HIV RNA and DNA levels compared to protease inhibitor-based therapy

Author

O Erlwein, A Winston, Peter Reiss, J Villaudy, B Berkhout, M. van der Valk, DP Benschop, A Kalsbeek, Ben Berkhout, M Martens, C Kingsley, T Booiman, Neeltje A. Kootstra, M Wezel, M Moreno-Villanueva, Paolo Garagnani, N Doyle, S Salvioli, BC Elsenga, JA ter Stege, T van der Kuyl, T Su, FR Janssen, BA Schmand, MM Mangas Ruiz, T Sindlinger, I Maurer, A Bürkle, M Capri, W Zikkenheiner, C Libert, M Chiricolo, Robert Leech, Ferdinand Wnm Wit, J Pothof, Caroline A. Sabin, Cblm Majoie, M Gisslén, A Lovell, Mmj Hillebregt, S Zaheri, I Visser, Claudio Franceschi, M de Graaff-Teulen, Alexander O. Pasternak, S Kovalev, M Prins, M Totté, NA Kootstra, H Zetterberg, D de Francesco, JH Cole, K Legg, Mwa Caan, J Schouten, M Klein Twennaar, Jelmer Vroom, J Berkel, AF Girigorie, P Reiss, S Moll, S Dewaele, K Weijer, D Fuchs, Marijn de Bruin, Alan Winston, Chiara Pirazzini, R.A. van Zoest, F Dall'Olio, Davide De Francesco, David J. Sharp, A Keller, AM Harskamp-Holwerda, J Underwood, F. W. Wit, GJ Geurtsen, P Portegies, Ymc Ruijs, M Stott, Margreet Bakker, M Heidenrijk, KW Kooij, Phlt Bisschop, G Guaraldi, L McDonald, C Sabin, AO Pasternak, J Hoeijmakers, Jan M. Prins, HG Ruhé, E Frankin, D Burger, Commission of the European Communities, National Institute for Health Research, and Pasternak AO, Vroom J, Kootstra NA, Wit FW, de Bruin M, De Francesco D, Bakker M, Sabin CA, Winston A, Prins JM, Reiss P, Berkhout B. Collaboratori C Franceschi, P Garagnani, C Pirazzini, M Capri, F Dall'Olio, M Chiricolo, S Salvioli

Subjects
Life Sciences & Biomedicine - Other Topics, DYNAMICS, Male, PROVIRUSES PRODUCE, medicine, Time Factors, Co-morBidity in Relation to Aids (COBRA) Collaboration, HIV Infections, Virus Replication, 0601 Biochemistry and Cell Biology, Nucleoside Reverse Transcriptase Inhibitor, chemistry.chemical_compound, Transcription (biology), virus infection, Biology (General), Randomized Controlled Trials as Topic, INFECTED PATIENTS, Reverse-transcriptase inhibitor, General Neuroscience, virus diseases, General Medicine, Middle Aged, Viral Load, Europe, Treatment Outcome, viru, RNA, Viral, Reverse Transcriptase Inhibitors, Drug Therapy, Combination, Female, Life Sciences & Biomedicine, medicine.drug, Adult, antiviral drug, Nevirapine, Efavirenz, QH301-705.5, RALTEGRAVIR INTENSIFICATION, Science, infectious disease, VIREMIA, virus, General Biochemistry, Genetics and Molecular Biology, Virus, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], antiviral drugs, All institutes and research themes of the Radboud University Medical Center, Humans, Protease inhibitor (pharmacology), Biology, Science & Technology, General Immunology and Microbiology, business.industry, PERSISTENCE, microbiology, RNA, HIV, HIV Protease Inhibitors, Virology, IMMUNE ACTIVATION, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Cross-Sectional Studies, chemistry, REPLICATION, DNA, Viral, RESERVOIR, business, DECAY
Abstract

Background:It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress human immunodeficiency virus (HIV) replication. Here, we report the results of two cross-sectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI).Methods:CA HIV unspliced RNA and total HIV DNA were quantified in two cohorts (n = 100, n = 124) of individuals treated with triple ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an NNRTI or a PI. To compare CA HIV RNA and DNA levels between the regimens, we built multivariable models adjusting for age, gender, current and nadir CD4+ count, plasma viral load zenith, duration of virological suppression, NRTI backbone composition, low-level plasma HIV RNA detectability, and electronically measured adherence to ART.Results:In both cohorts, levels of CA HIV RNA and DNA strongly correlated (rho = 0.70 and rho = 0.54) and both markers were lower in NNRTI-treated than in PI-treated individuals. In the multivariable analysis, CA RNA in both cohorts remained significantly reduced in NNRTI-treated individuals (padj = 0.02 in both cohorts), with a similar but weaker association between the ART regimen and total HIV DNA (padj = 0.048 and padj = 0.10). No differences in CA HIV RNA or DNA levels were observed between individual NNRTIs or individual PIs, but CA HIV RNA was lower in individuals treated with either nevirapine or efavirenz, compared to PI-treated individuals.Conclusions:All current classes of antiretroviral drugs only prevent infection of new cells but do not inhibit HIV RNA transcription in long-lived reservoir cells. Therefore, these differences in CA HIV RNA and DNA levels by treatment regimen suggest that NNRTIs are more potent in suppressing HIV residual replication than PIs, which may result in a smaller viral reservoir size.Funding:This work was supported by ZonMw (09120011910035) and FP7 Health (305522).

Published
2021

9. Hierarchical modeling of indoor radon concentration: how much do geology and building factors matter?

Author

Davide De Francesco, Nikos Tzavidis, Daniela de Bartolo, Riccardo Borgoni, Borgoni, R, De Francesco, D, DE BARTOLO, D, and Tzavidis, N

Subjects
Pollution, Health, Toxicology and Mutagenesis, media_common.quotation_subject, chemistry.chemical_element, Radon, Soil, Natural gas, Floor effect, Environmental Chemistry, Waste Management and Disposal, Background radiation, media_common, Hierarchical modeling, business.industry, Construction Materials, Soil gas, Environmental engineering, Floor level, General Medicine, Indoor radon concentration, Models, Theoretical, Building factor, Residential radon, Construction Material, Hierarchical mixed model, chemistry, Italy, Air Pollutants, Radioactive, Air Pollution, Indoor, Housing, business, Geology
Abstract

Radon is a natural gas known to be the main contributor to natural background radiation exposure and only second to smoking as major leading cause of lung cancer. The main concern is in indoor environments where the gas tends to accumulate and can reach high concentrations. The primary contributor of this gas into the building is from the soil although architectonic characteristics, such as building materials, can largely affect concentration values. Understanding the factors affecting the concentration in dwellings and workplaces is important both in prevention, when the construction of a new building is being planned, and in mitigation when the amount of Radon detected inside a building is too high. In this paper we investigate how several factors, such as geologic typologies of the soil and a range of building characteristics, impact on indoor concentration focusing, in particular, on how concentration changes as a function of the floor level. Adopting a mixed effects model to account for the hierarchical nature of the data, we also quantify the extent to which such measurable factors manage to explain the variability of indoor radon concentration.

Published
2014

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