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1. Promoting HIV indicator condition-guided testing in hospital settings (PROTEST 2.0): study protocol for a multicentre interventional study

Author

Bogers, Saskia J., Schim van der Loeff, Maarten F., Davidovich, Udi, Boyd, Anders, van der Valk, Marc, Brinkman, Kees, de Bree, Godelieve J., Reiss, Peter, van Bergen, Jan E. A. M., Geerlings, Suzanne E., van Bergen, J. E. A. M., Brokx, P., Deug, F., Heidenrijk, M., Prins, M., Reiss, P., van der Valk, M., de Bree, G. J., Geerlings, S. E., Hoornenborg, E., Achterbergh, R. C. A., Ananworanich, J., van de Beek, D., Brinkman, N., de Bruin, M., Bruisten, S., Coyer, L., Dijkstra, M., Geijtenbeek, T. B. H., Godfried, M. H., Goorhuis, A., Hankins, C. A., Hogewoning, A., Hovius, J. W., de Jong, K., Kootstra, N. A., Lauw, F., van der Meer, J. T., Mulder, B. J., Nellen, F. J., Peters, E., van der Poll, T., van Rooijen, M. S., Sonder, G. J., de Vries, H. J., van Vugt, M., Wiersinga, W. J., Wit, F. W., Zantkuijl, P., Graduate School, Vascular Medicine, AII - Infectious diseases, Infectious diseases, APH - Aging & Later Life, APH - Global Health, Global Health, General practice, APH - Methodology, APH - Quality of Care, Medical Microbiology and Infection Prevention, Neurology, Amsterdam Neuroscience - Neuroinfection & -inflammation, Experimental Immunology, Center of Experimental and Molecular Medicine, Dermatology, APH - Digital Health, APH - Personalized Medicine, Sociale Psychologie (Psychologie, FMG), Psychology Other Research (FMG), Stichting Aidsfonds, Virology, Medical Microbiology & Infectious Diseases, and Internal Medicine

Subjects
medicine.medical_specialty, Pediatrics, Tuberculosis, Multifaceted intervention, HIV Positivity, HIV Transmission Elimination AMsterdam (H-TEAM) Consortium, HIV Infections, Infectious and parasitic diseases, RC109-216, Indicator condition, Healthcare quality improvement, Microbiology, 03 medical and health sciences, Study Protocol, 0302 clinical medicine, Medical microbiology, SDG 3 - Good Health and Well-being, 1108 Medical Microbiology, Intervention (counseling), medicine, Clinical endpoint, Prevalence, Humans, Mass Screening, 030212 general & internal medicine, Netherlands, 030505 public health, business.industry, Patient Selection, virus diseases, 1103 Clinical Sciences, Hepatitis B, Vulvar cancer, medicine.disease, Hospitals, HIV testing, Infectious Diseases, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Implementation, Tropical medicine, 0305 other medical science, business, 0605 Microbiology
Abstract

Background Late presentation remains a key barrier towards controlling the HIV epidemic. Indicator conditions (ICs) are those that are AIDS-defining, associated with a prevalence of undiagnosed HIV > 0.1%, or whose clinical management would be impeded if an HIV infection were undiagnosed. IC-guided HIV testing is an effective strategy in identifying undiagnosed HIV, but opportunities for earlier HIV diagnosis through IC-guided testing are being missed. We present a protocol for an interventional study to improve awareness of IC-guided testing and increase HIV testing in patients presenting with ICs in a hospital setting. Methods We designed a multicentre interventional study to be implemented at five hospitals in the region of Amsterdam, the Netherlands. Seven ICs were selected for which HIV test ratios (proportion of patients with an IC tested for HIV) will be measured: tuberculosis, cervical/vulvar cancer or high-grade cervical/vulvar dysplasia, malignant lymphoma, hepatitis B and C, and peripheral neuropathy. Prior to the intervention, a baseline assessment of HIV test ratios across ICs will be performed in eligible patients (IC diagnosed January 2015 through May 2020, ≥18 years, not known HIV positive) and an assessment of barriers and facilitators for HIV testing amongst relevant specialties will be conducted using qualitative (interviews) and quantitative methods (questionnaires). The intervention phase will consist of an educational intervention, including presentation of baseline results as competitive graphical audit and feedback combined with discussion on implementation and opportunities for improvement. The effect of the intervention will be assessed by comparing HIV test ratios of the pre-intervention and post-intervention periods. The primary endpoint is the HIV test ratio within ±3 months of IC diagnosis. Secondary endpoints are the HIV test ratio within ±6 months of diagnosis, ratio ever tested for HIV, HIV positivity percentage, proportion of late presenters and proportion with known HIV status prior to initiating treatment for their IC. Discussion This protocol presents a strategy aimed at increasing awareness of the benefits of IC-guided testing and increasing HIV testing in patients presenting with ICs in hospital settings to identify undiagnosed HIV in Amsterdam, the Netherlands. Trial registration Dutch trial registry: NL7521. Registered 14 February 2019.

Published
2021

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. Is reaching 90-90-90 enough to end AIDS? Lessons from Amsterdam

Author

Bree, G.J. de, Sighem, A. van, Zuilhof, W., Bergen, J.E.A.M. van, Prins, M., Heidenrijk, M., Valk, M. van der, Brokx, P., Reiss, P., Deug, F., Davidovich, U., Geerlings, S.E., Hoornenborg, E., Oomen, A., Bruinderink, M.L.G., Schat, N., Achterbergh, R.C.A., Agtmael, M. van, Ananworanich, J., Beek, D. van de, Berk, G.E.L. van den, Bezemer, D., Bijnen, A. van, Blok, W.L., Bogers, S., Bomers, M., Boucher, C.A.B., Brokking, W., Burger, D., Brinkman, K., Brinkman, N., Bruin, M. de, Bruisten, S., Coyer, L., Crevel, R. van, Daans, C.G., Derckx, T., Dijkstra, M., Duijnhoven, Y.T. van, Eeden, A. van, Elsenburg, L., Elshout, M.A.M. van den, Ester, C., Ersan, E., Felipa, P.E.V., Geijtenbeek, T.B.H., Gool, J. van, Goorhuis, A., Groot, M., Hankins, C.A., Heijnen, A., Hillebregt, M.M.J., Hogewoning, A., Hommenga, M., Hovius, J.W., Janssen, Y., Jong, K. de, Jongen, V., Kootstra, N.A., Koup, R.A., Kroon, F.P., Laar, T.J.W. van de, Lauw, F., Leeuwen, M.M. van, Lettinga, K., Linde, I., Loomans, D.S.E., Mouhebati, T., Mulder, B.J., Mulder, J., Nellen, F.J., Nijsters, A., Nobel, H., Oostvogel, P., Coul, E.L.M. op de, Peters, E., Peters, I.S., Poll, T. van der, Ratmann, O., Rokx, C., Rooijen, M.S. van, Loeff, M.F.S. van der, Schoute, W.E.M., Sonder, G.J., Veenstra, J., Verbon, A., Vries, H.J. de, Vrouenraets, S., Vugt, M. van, Wiersinga, W.J., Wit, F.W., Zaheri, S., Zantkuijl, P., Zelm, M.C. van, Zakowicz, A., Zimmermann, H.M.L., HIV Transmission Elimination, Virology, and Internal Medicine

Subjects
0301 basic medicine, medicine.medical_specialty, Anti-HIV Agents, Immunology, Human immunodeficiency virus (HIV), MEDLINE, Hiv testing, medicine.disease_cause, epidemic, 03 medical and health sciences, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, Virology, Environmental health, Medicine, Humans, 030212 general & internal medicine, Amsterdam, Hiv transmission, Netherlands, Acquired Immunodeficiency Syndrome, Oncology (nursing), business.industry, Transmission (medicine), Public health, virus diseases, HIV, Hematology, Integrated approach, medicine.disease, 030104 developmental biology, Infectious Diseases, Oncology, business
Abstract

Purpose of review Although cities present opportunities for infectious pathogens such as HIV to spread, public health infrastructure within these cities also provides opportunities to design effective approaches to eliminate transmission of these pathogens. The HIV Transmission Elimination AMsterdam (H-TEAM) Initiative, a consortium of relevant stakeholders involved in HIV prevention and care, designed an integrated approach to curb the HIV epidemic in Amsterdam, including providing preexposure prophylaxis (PrEP), increasing awareness of acute HIV infection, offering same-day test and treat, and improving indicator disease-driven HIV testing. Recent findings In 2013, approximately 230 people in Amsterdam were newly diagnosed with HIV, largely belonging to one of two key affected populations, namely MSM and people with a migration background. Since the start of H-TEAM in 2014, a decrease in new diagnoses was observed (130 in 2017), with an increasing proportion of MSM who had been diagnosed with a recent infection. Summary The H-TEAM shows that a city-based concerted effort is feasible. However, major challenges remain, such as reducing the number of late HIV diagnoses, and identifying and providing appropriate services to a diminishing group of individuals who are likely the source of transmission.

Published
2019

4. 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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