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2. Prevalence and Outcomes for Heavily Treatment-Experienced Individuals Living With Human Immunodeficiency Virus in a European Cohort

Author

Pelchen-Matthews, A., Borges, A. H., Reekie, J., Rasmussen, L. D., Wiese, L., Weber, J., Pradier, C., Degen, O., Paredes, R., Tau, L., Flamholc, L., Gottfredsson, M., Kowalska, J. D., Jablonowska, E., Mozer-Lisewska, I., Radoi, R., Vasylyev, M., Kuznetsova, A., Begovac, J., Svedhem, V., Clark, A., Cozzi-Lepri, A., Harxhi, A., Losso, M., Kundro, M., Schmied, B., Zangerle, R., Karpov, I., Vassilenko, A., Mitsura, V. M., Paduto, D., Clumeck, N., De Wit, S., Delforge, M., Florence, E., Vandekerckhove, L., Hadziosmanovic, V., Machala, L., Jilich, D., Sedlacek, D., Kronborg, G., Benfield, T., Gerstoft, J., Katzenstein, T., Pedersen, C., Johansen, I. S., Ostergaard, L., Moller, N. F., Nielsen, L. N., Zilmer, K., Smidt, J., Aho, I., Viard, J. -P., Girard, P. -M., Fontas, E., Duvivier, C., Rockstroh, J., Behrens, G., Stellbrink, H. J., Stephan, C., Goethe, J. W., Bogner, J., Fatkenheuer, G., Chkhartishvili, N., Sambatakou, H., Adamis, G., Paissios, N., Szlavik, J., Kelly, C., Turner, D., Burke, M., Shahar, E., Hassoun, G., Elinav, H., Haouzi, M., Elbirt, D., D'Arminio Monforte, A., Esposito, R., Mazeu, I., Mussini, C., Mazzotta, F., Gabbuti, A., Lazzarin, A., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., Uzdaviniene, V., Matulionyte, R., Staub, T., Hemmer, R., Dragas, S., Stevanovic, M., Reiss, P., Trajanovska, J., Reikvam, D. H., Maeland, A., Bruun, J., Knysz, B., Gasiorowski, J., Inglot, M., Bakowska, E., Flisiak, R., Grzeszczuk, A., Parczewski, M., Maciejewska, K., Aksak-Was, B., Beniowski, M., Mularska, E., Kamerys, J., Wojcik, K., Rozplochowski, B., Zagalo, A., Mansinho, K., Maltez, F., Oprea, C., Yakovlev, A., Trofimora, T., Khromova, I., Kuzovatova, E., Borodulina, E., Vdoushkina, E., Ranin, J., Tomazic, J., Miro, J. M., Laguno, M., Martinez, E., Garcia, F., Blanco, J. L., Martinez-Rebollar, M., Mallolas, J., Callau, P., Rojas, J., Inciarta, A., Moreno, S., del Campo, S., Clotet, B., Jou, A., Puig, J., Llibre, J. M., Santos, J. R., Domingo, P., Gutierrez, M., Mateo, G., Sambeat, M. A., Laporte, J. M., Falconer, K., Thalme, A., Sonnerborg, A., Treutiger, C. J., Scherrer, A., Weber, R., Cavassini, M., Calmy, A., Furrer, H., Battegay, M., Schmid, P., Mikhalik, J., Sluzhynska, M., Milinkovic, A., Johnson, A. M., Simons, E., Edwards, S., Phillips, A., Johnson, M. A., Mocroft, A., Orkin, C., Winston, A., Leen, C., Wandeler, G., Lundgren, J., Guaraldi, G., Kirk, O., Peters, L., Bojesen, A., Raben, D., Hansen, E. V., Kristensen, D., Larsen, J. F., Fischer, A. H., Amele, S., and Roen, A.

Subjects
Adult, Male, antiretroviral treatment, medicine.medical_specialty, Anti-HIV Agents, Human immunodeficiency virus (HIV), non-AIDS-defining clinical conditions, Comorbidity, Rate ratio, medicine.disease_cause, symbols.namesake, heavily treatment experienced, Acquired immunodeficiency syndrome (AIDS), Antiretroviral Therapy, Highly Active, Internal medicine, medicine, Humans, Pharmacology (medical), Prospective Studies, Poisson regression, Prospective cohort study, Acquired Immunodeficiency Syndrome, business.industry, Confounding, HIV resistance, acquired immunodeficiency syndrome, Middle Aged, Viral Load, prevalence, outcomes, heavily, treatment-experienced, individuals, HIV, medicine.disease, Europe, AIDS, Treatment Outcome, Infectious Diseases, Cohort, symbols, Female, business, Viral load
Abstract

Background: Although antiretroviral treatments have improved survival of persons living with HIV, their long-term use may limit available drug options. We estimated the prevalence of heavily treatment-experienced (HTE) status and the potential clinical consequences of becoming HTE. Setting: EuroSIDA, a European multicenter prospective cohort study. Methods: A composite definition for HTE was developed, based on estimates of antiretroviral resistance and prior exposure to specific antiretroviral regimens. Risks of progressing to clinical outcomes were assessed by Poisson regression, comparing every HTE individual with 3 randomly selected controls who never became HTE. Results: Of 15,570 individuals under follow-up in 2010-2016, 1617 (10.4%, 95% CI: 9.9% to 10.9%) were classified as HTE. 1093 individuals became HTE during prospective follow-up (HTE incidence rate 1.76, CI: 1.66 to 1.87 per 100 person-years of follow-up). The number of HTE individuals was highest in West/Central Europe (636/4019 persons, 15.7%) and lowest in East Europe (26/2279 persons, 1.1%). Although most HTE individuals maintained controlled viral loads (

Published
2021
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3. Incidence of cancer and overall risk of mortality in individuals treated with raltegravir‐based and non‐raltegravir‐based combination antiretroviral therapy regimens

Author

Cozzi‐Lepri, A, Zangerle, R, Machala, L, Zilmer, K, Ristola, M, Pradier, C, Kirk, O, Sambatakou, H, Fätkenheuer, G, Yust, I, Schmid, P, Gottfredsson, M, Khromova, I, Jilich, D, Flisiak, R, Smidt, J, Rozentale, B, Radoi, R, Losso, MH, Lundgren, JD, Mocroft, A, Kundro, M., Schmied, B., Karpov, I., Vassilenko, A., Mitsura, V. M., Paduto, D., Clumeck, N., De Wit, S., Delforge, M., Florence, E., Vandekerckhove, L., Hadziosmanovic, V., Begovac, J., Sedlacek, D., Kronborg, G., Benfield, T., Gerstoft, J., Katzenstein, T., Møller, N. F., Pedersen, C., Ostergaard, L., Wiese, L., Nielsen, L. N., Aho, I., Viard, J.‐P., Girard, P.‐M., Fontas, E., Duvivier, C., Rockstroh, J., Schmidt, R., Degen, O., Stellbrink, H. J., Stefan, C., Bogner, J., Chkhartishvili, N., Gargalianos, P., Xylomenos, G., Lourida, P., Szlávik, J., Mulcahy, F., Turner, D., Burke, M., Shahar, E., Hassoun, G., Elinav, H., Haouzi, M., Elbirt, D., Sthoeger, Z. M., DʼArminio Monforte, A., Esposito, R., Mazeu, I., Mussini, C., Mazzotta, F., Gabbuti, A., Vullo, V., Lichtner, M., Zaccarelli, M., Antinori, A., Acinapura, R., Plazzi, M., Lazzarin, A., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., Uzdaviniene, V., Matulionyte, R., Staub, T., Hemmer, R., Reiss, P., Ormaasen, V., Maeland, A., Bruun, J., Knysz, B., Gasiorowski, J., Inglot, M., Horban, A., Bakowska, E., Grzeszczuk, A., Parczewski, M., Maciejewska, K., Aksak‐Was, B., Beniowski, M., Mularska, E., Smiatacz, T., Gensing, M., Jablonowska, E., Malolepsza, E., Wojcik, K., Mozer‐Lisewska, I., Caldeira, L., Mansinho, K., Maltez, F., Oprea, C., Panteleev, A., Panteleev, O., Yakovlev, A., Trofimora, T., Kuzovatova, E., Borodulina, E., Vdoushkina, E., Jevtovic, D., Tomazic, J., Gatell, J. M., Miró, J. M., Moreno, S., Rodriguez, J. M., Clotet, B., Jou, A., Paredes, R., Tural, C., Puig, J., Bravo, I., Domingo, P., Gutierrez, M., Mateo, G., Sambeat, M. A., Laporte, J. M., Falconer, K., Thalme, A., Sonnerborg, A., Blaxhult, A., Flamholc, L., Scherrer, A., Weber, R., Cavassini, M., Calmy, A., Furrer, H., Battegay, M., Kuznetsova, A., Kyselyova, G., Sluzhynska, M., Gazzard, B., Johnson, A. M., Simons, E., Edwards, S., Phillips, A., Johnson, M. A., Orkin, C., Weber, J., Scullard, G., Clarke, A., Leen, C., Thiebaut, R., Burger, D., Peters, L., Matthews, C., Fischer, A. H., Bojesen, A., Raben, D., Kristensen, D., Grønborg Laut, K., Larsen, J. F., Podlekareva, D., Shepherd, L., Schultze, A., and Amele, S.

Published
2018
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4. Incidence of hypertension in people with HIV who are treated with integrase inhibitors versus other antiretroviral regimens in the RESPOND cohort consortium

Author

Byonanebye, Dathan M., Polizzotto, Mark N., Neesgaard, Bastian, Sarcletti, Mario, Matulionyte, Raimonda, Braun, Dominique L., Castagna, Antonella, de Wit, Stéphane, Wit, Ferdinand, Fontas, Eric, Vehreschild, J. rg Janne, Vesterbacka, Jan, Greenberg, Lauren, Hatleberg, Camilla, Garges, Harmony, Gallant, Joel, Volny Anne, Alain, Öllinger, Angela, Mozer-Lisewska, Iwona, Surial, Bernard, Spagnuolo, Vincenzo, Necsoi, Coca, van der Valk, Marc, Mocroft, Amanda, Law, Matthew, Ryom, Lene, Petoumenos, Kathy, Hillebregt, M., Rose, N., Hutchinson, J., Zangerle, R., Appoyer, H., Delforge, M., Stephan, C., Bucht, M., Chkhartishvili, N., Chokoshvili, O., Mussini, C., Borghi, V., Pradier, C., Dollet, K., Caissotti, C., Casabona, J., Miro, J. M., Smith, C., Lampe, F., Johnson, M., Burns, F., Chaloner, C., Lazzarin, A., Poli, A., Sönnerborg, A., Falconer, K., Svedhem, V., Günthard, H., Ledergerber, B., Bucher, H., Scherrer, A., Wasmuth, J. C., Rockstroh, J., Fätkenheuer, G., Stecher, M., Schulze, N., Franke, B., Rooney, J., McNicholl, I., Vannappagari, V., Wandeler, G., Lundgren, J., Kowalska, J., Raben, D., Mocroft, A., Peters, L., Williams, E. D., Necsoi, C., D’Arminio Monforte, A., Bruguera, A., Dedes, Nikos, Mendao, Luis, Larsen, J. F., Jaschinski, N., Jakobsen, M. L., Bruun, T., Bojesen, A., Hansen, E. V., Traytel, A. K., Elsing, T. W., Kristensen, D., Weide, T., Bansi-Matharu, L., Pelchen-Matthews, A., Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, APH - Digital Health, APH - Personalized Medicine, and APH - Global Health

Subjects
Adult, Aged, 80 and over, HIV, antiretroviral agents, hypertension, integrase inhibitors, Adolescent, Anti-HIV Agents, Health Policy, Incidence, virus diseases, 610 Medicine & health, HIV Infections, Integrase Inhibitors, Infectious Diseases, Anti-Retroviral Agents, Hypertension, Humans, Reverse Transcriptase Inhibitors, Pharmacology (medical), HIV Integrase Inhibitors
Abstract

OBJECTIVE To compare the incidence of hypertension in people living with HIV receiving integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) versus non-nucleoside reverse transcriptase inhibitors (NNRTIs) or boosted protease inhibitors (PIs) in the RESPOND consortium of HIV cohorts. METHODS Eligible people with HIV were aged ���18��years who initiated a new three-drug ART regimen for the first time (baseline), did not have hypertension, and had at least two follow-up blood pressure (BP) measurements. Hypertension was defined as two consecutive systolic BP measurements ���140��mmHg and/or diastolic BP ���90��mmHg or initiation of antihypertensives. Multivariable Poisson regression was used to determine adjusted incidence rate ratios (aIRRs) of hypertension, overall and in those who were ART na��ve or experienced at baseline. RESULTS Overall, 4606 people living with HIV were eligible (INSTIs��3164, NNRTIs��807, PIs��635). The median baseline systolic BP, diastolic BP, and age were 120 (interquartile range [IQR] 113-130) mmHg, 78 (70-82) mmHg, and 43 (34-50) years, respectively. Over 8380.4 person-years (median follow-up 1.5 [IQR 1.0-2.7]��years), 1058 (23.0%) participants developed hypertension (incidence rate 126.2/1000 person-years, 95% confidence interval [CI] 118.9-134.1). Participants receiving INSTIs had a higher incidence of hypertension than those receiving NNRTIs (aIRR 1.76; 95% CI 1.47-2.11), whereas the incidence was no different in those receiving PIs (aIRR 1.07; 95% CI 0.89-1.29). The results were similar when the analysis was stratified by ART status at baseline. CONCLUSION Although unmeasured confounding and channelling bias cannot be excluded, INSTIs were associated with a higher incidence of hypertension than were NNRTIs, but rates were similar to those of PIs overall, in ART-na��ve and ART-experienced participants within RESPOND.

Published
2022
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5. HCV reinfection after HCV therapy among HIV/HCV-coinfected individuals in Europe

Author

Amele, S., Sandri, A. K., Rodger, A., Vandekerckhove, L., Benfield, T., Milinkovic, A., Duvivier, C., Stellbrink, H. -J., Sambatakou, H., Chkhartishvili, N., Caldeira, L., Laguno, M., Domingo, P., Wandeler, G., Gisinger, M., Kuzovatova, E., Dragovic, G., Knysz, B., Matulionyte, R., Rockstroh, J. K., Lundgren, J. D., Mocroft, A., Peters, L., Harxhi, A., Losso, M., Kundro, M., Schmied, B., Zangerle, R., Karpov, I., Vassilenko, A., Mitsura, V. M., Paduto, D., Clumeck, N., Wit, S. D., Delforge, M., Florence, E., Hadziosmanovic, V., Begovac, J., Machala, L., Jilich, D., Sedlacek, D., Kronborg, G., Gerstoft, J., Katzenstein, T., Pedersen, C., Johansen, I. S., Ostergaard, L., Wiese, L., Moller, N. F., Nielsen, L. N., Zilmer, K., Smidt, J., Aho, I., Viard, J. -P., Girard, P. -M., Pradier, C., Fontas, E., Rockstroh, J., Behrens, G., Degen, O., Stellbrink, H. J., Stefan, C., Bogner, J., Fatkenheuer, G., Adamis, G., Paissios, N., Szlavik, J., Gottfredsson, M., Devitt, E., Tau, L., Turner, D., Burke, M., Shahar, E., Hassoun, G., Elinav, H., Haouzi, M., Elbirt, D., D'Arminio Monforte, A., Esposito, R., Mazeu, I., Mussini, C., Mazzotta, F., Gabbuti, A., Lazzarin, A., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., Sacco, L., Uzdaviniene, V., Staub, T., Hemmer, R., Dragas, S., Stevanovic, M., Reiss, P., Trajanovska, J., Reikvam, D. H., Maeland, A., Bruun, J., Gasiorowski, J., Inglot, M., Bakowska, E., Flisiak, R., Grzeszczuk, A., Parczewski, M., Maciejewska, K., Aksak-Was, B., Beniowski, M., Mularska, E., Jablonowska, E., Kamerys, J., Wojcik, K., Mozer-Lisewska, I., Rozplochowski, B., Zagalo, A., Mansinho, K., Maltez, F., Radoi, R., Oprea, C., Davila, C., Yakovlev, A., Trofimora, T., Khromova, I., Blokhina, I. N., Novogrod, N., Borodulina, E., Vdoushkina, E., Ranin, J., Tomazic, J., Miro, J. M., Martinez, E., Garcia, F., Blanco, J. L., Martinez-Rebollar, M., Mallolas, J., Callau, P., Rojas, J., Inciarta, A., Moreno, S., del Campo, S., Clotet, B., Jou, A., Paredes, R., Puig, J., Llibre, J. M., Santos, J. R., Gutierrez, M., Mateo, G., Sambeat, M. A., Laporte, J. M., Falconer, K., Thalme, A., Sonnerborg, A., Brannstrom, J., Flamholc, L., Scherrer, A., Weber, R., Cavassini, M., Calmy, A., Furrer, H., Battegay, M., Schmid, P., Kuznetsova, A., Mikhalik, J., Sluzhynska, M., Johnson, A. M., Simons, E., Edwards, S., Phillips, A., Johnson, M. A., Orkin, C., Winston, A., Clarke, A., Leen, C., Lundgren, J., Rasmussen, L. D., Svedhem, V., Kowalska, J. D., Guaraldi, G., Kirk, O., Bojesen, A., Raben, D., Hansen, E. V., Kristensen, D., Larsen, J. F., Fischer, A. H., Cozzi-Lepri, A., Pelchen-Matthews, A., Roen, A., Tusch, E., Bannister, W., Reekie, J., Amele, S., Sandri, A. K., Rodger, A., Vandekerckhove, L., Benfield, T., Milinkovic, A., Duvivier, C., Stellbrink, H. -J., Sambatakou, H., Chkhartishvili, N., Caldeira, L., Laguno, M., Domingo, P., Wandeler, G., Gisinger, M., Kuzovatova, E., Dragovic, G., Knysz, B., Matulionyte, R., Rockstroh, J. K., Lundgren, J. D., Mocroft, A., Peters, L., Harxhi, A., Losso, M., Kundro, M., Schmied, B., Zangerle, R., Karpov, I., Vassilenko, A., Mitsura, V. M., Paduto, D., Clumeck, N., Wit, S. D., Delforge, M., Florence, E., Hadziosmanovic, V., Begovac, J., Machala, L., Jilich, D., Sedlacek, D., Kronborg, G., Gerstoft, J., Katzenstein, T., Pedersen, C., Johansen, I. S., Ostergaard, L., Wiese, L., Moller, N. F., Nielsen, L. N., Zilmer, K., Smidt, J., Aho, I., Viard, J. -P., Girard, P. -M., Pradier, C., Fontas, E., Rockstroh, J., Behrens, G., Degen, O., Stellbrink, H. J., Stefan, C., Bogner, J., Fatkenheuer, G., Adamis, G., Paissios, N., Szlavik, J., Gottfredsson, M., Devitt, E., Tau, L., Turner, D., Burke, M., Shahar, E., Hassoun, G., Elinav, H., Haouzi, M., Elbirt, D., D'Arminio Monforte, A., Esposito, R., Mazeu, I., Mussini, C., Mazzotta, F., Gabbuti, A., Lazzarin, A., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., Sacco, L., Uzdaviniene, V., Staub, T., Hemmer, R., Dragas, S., Stevanovic, M., Reiss, P., Trajanovska, J., Reikvam, D. H., Maeland, A., Bruun, J., Gasiorowski, J., Inglot, M., Bakowska, E., Flisiak, R., Grzeszczuk, A., Parczewski, M., Maciejewska, K., Aksak-Was, B., Beniowski, M., Mularska, E., Jablonowska, E., Kamerys, J., Wojcik, K., Mozer-Lisewska, I., Rozplochowski, B., Zagalo, A., Mansinho, K., Maltez, F., Radoi, R., Oprea, C., Davila, C., Yakovlev, A., Trofimora, T., Khromova, I., Blokhina, I. N., Novogrod, N., Borodulina, E., Vdoushkina, E., Ranin, J., Tomazic, J., Miro, J. M., Martinez, E., Garcia, F., Blanco, J. L., Martinez-Rebollar, M., Mallolas, J., Callau, P., Rojas, J., Inciarta, A., Moreno, S., del Campo, S., Clotet, B., Jou, A., Paredes, R., Puig, J., Llibre, J. M., Santos, J. R., Gutierrez, M., Mateo, G., Sambeat, M. A., Laporte, J. M., Falconer, K., Thalme, A., Sonnerborg, A., Brannstrom, J., Flamholc, L., Scherrer, A., Weber, R., Cavassini, M., Calmy, A., Furrer, H., Battegay, M., Schmid, P., Kuznetsova, A., Mikhalik, J., Sluzhynska, M., Johnson, A. M., Simons, E., Edwards, S., Phillips, A., Johnson, M. A., Orkin, C., Winston, A., Clarke, A., Leen, C., Lundgren, J., Rasmussen, L. D., Svedhem, V., Kowalska, J. D., Guaraldi, G., Kirk, O., Bojesen, A., Raben, D., Hansen, E. V., Kristensen, D., Larsen, J. F., Fischer, A. H., Cozzi-Lepri, A., Pelchen-Matthews, A., Roen, A., Tusch, E., Bannister, W., Reekie, J., Global Health, Infectious diseases, AII - Infectious diseases, and APH - Aging & Later Life

Subjects
Male, direct-acting antivirals, HCV, HIV, interferon, reinfection, HIV Infections, Hepacivirus, Antiviral Agents, 03 medical and health sciences, 0302 clinical medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, 0303 health sciences, Coinfection, 030306 microbiology, Health Policy, virus diseases, Hepatitis C, Chronic, Middle Aged, 3. Good health, Europe, Infectious Diseases, Reinfection, Female
Abstract

Objectives: Although direct-acting antivirals (DAAs) can clear HCV in nearly all HIV/HCV-coinfected individuals, high rates of reinfection may hamper efforts to eliminate HCV in this population. We investigated reinfection after sustained virological response (SVR) in HIV/HCV-coinfected individuals in Europe. Methods: Factors associated with odds of reinfection by 2years after SVR in EuroSIDA participants with one or more HCV-RNA test and 2years follow-up were assessed using logistic regression. Results: Overall, 1022 individuals were included. The median age was 50 (interquartile range: 43–54years), and most were male (78%), injection drug users (52%), and received interferon (IFN)-free DAAs (62%). By 24months, 75 [7.3%, 95% confidence interval (CI): 5.7–8.9%] individuals were reinfected. Among individuals treated prior to 2014, 16.1% were reinfected compared with 4.2% and 8.3%, respectively, among those treated during or after 2014 with IFN-free and IFN-based therapy. After adjustment, individuals who had started treatment during or after 2014 with IFN-free or IFN-based therapy had significantly lower odds of reinfection (adjusted odds ratio = 0.21, 95% CI: 0.11–0.38; 0.43, 95% CI: 0.22–0.83) compared with those who had received therapy before 2014. There were no significant differences in odds of reinfection according to age, gender, European region, HIV transmission risk group or liver fibrosis. Conclusions: Among HIV/HCV-coinfected individuals in Europe, 7.3% were reinfected with HCV within 24months of achieving SVR, with evidence suggesting that this is decreasing over time and with use of newer HCV regimens. Harm reduction to reduce reinfection and surveillance to detect early reinfection with an offer of treatment are essential to eliminate HCV.

Published
2021
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6. Establishing a hepatitis C continuum of care among HIV/hepatitis C virus-coinfected individuals in EuroSIDA

Author

Amele, S., Peters, L., Sluzhynska, M., Yakovlev, A., Scherrer, A., Domingo, P., Gerstoft, J., Viard, J. P., Gisinger, M., Flisiak, R., Bhaghani, S., Ristola, M., Leen, C., Jablonowska, E., Wandeler, G., Stellbrink, H., Falconer, K., D'Arminio Monforte, A., Horban, A., Rockstroh, J. K., Lundgren, J. D., Mocroft, A., Losso, M., Kundro, M., Schmied, B., Zangerle, R., Karpov, I., Vassilenko, A., Mitsura, V. M., Paduto, D., Clumeck, N., De Wit, S., Delforge, M., Florence, E., Vandekerckhove, L., Hadziosmanovic, V., Begovac, J., Machala, L., Jilich, D., Sedlacek, D., Kronborg, G., Benfield, T., Katzenstein, T., Pedersen, C., Johansen, I. S., Ostergaard, L., Wiese, L., Moller, N. F., Nielsen, L. N., Zilmer, K., Smidt, Jelena, Aho, I., Girard, P. -M., Pradier, C., Fontas, E., Duvivier, C., Behrens, G., Degen, O., Stefan, C., Bogner, J., Fätkenheuer, G., Chkhartishvili, N., Gargalianos, P., Xylomenos, G., Armenis, K., Sambatakou, H., Szlávik, J., Gottfredsson, M., Mulcahy, F., Yust, I., Turner, D., Burke, M., Shahar, E., Hassoun, G., Elinav, H., Haouzi, M., Elbirt, D., Sthoeger, Z. M., Esposito, R., Mazeu, I., Mussini, C., Mazzotta, F., Gabbuti, A., Vullo, V., Lichtner, M., Zaccarelli, M., Antinori, A., Acinapura, R., Plazzi, M., Lazzarin, A., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., Rozentale, B., Uzdaviniene, V., Matulionyte, R., Staub, T., Hemmer, R., Reiss, P., Reikvam, D. H., Maeland, A., Bruun, J., Knysz, B., Gasiorowski, J., Inglot, M., Bakowska, E., Grzeszczuk, A., Parczewski, M., Maciejewska, K., Aksak-Was, B., Beniowski, M., Mularska, E., Smiatacz, T., Gensing, M., Kamerys, J., Wojcik, K., Mozer-Lisewska, I., Caldeira, L., Mansinho, K., Maltez, F., Radoi, R., Oprea, C., Panteleev, A., Panteleev, O., Trofimora, T., Khromova, I., Kuzovatova, E., Borodulina, E., Vdoushkina, E., Jevtovic, D., Tomazic, J., Miro, J. M., Laguno, M., Martinez, E., Garcia, F., Blanco, J. L., Martinez-Rebollar, M., Mallolas, J., Moreno, S., Rodriguez, J. M., Clotet, B., Jou, A., Paredes, R., Tural, C., Puig, J., Bravo, I., Gutierrez, M., Mateo, G., Sambeat, M. A., Laporte, J. M., Sonnerborg, A., Treutiger, C. J., Flamholc, L., Weber, R., Cavassini, M., Calmy, A., Furrer, H., Battegay, M., Schmid, P., Kuznetsova, A., Kyselyova, G., Gazzard, B., Johnson, A. M., Simons, E., Edwards, S., Phillips, A., Johnson, M. A., Orkin, C., Weber, J., Scullard, G., Clarke, A., Rasmussen, L. D., Svedhem, V., Kowalska, J. D., Guaraldi, G., Kirk, O., Bojesen, A., Raben, D., Kristensen, D., Laut, K., Larsen, J. F., Podlekareva, D., Nykjær, B., Cozzi-Lepri, A., Pelchen-Matthews, A., Amele, S., Peters, L., Sluzhynska, M., Yakovlev, A., Scherrer, A., Domingo, P., Gerstoft, J., Viard, J. P., Gisinger, M., Flisiak, R., Bhaghani, S., Ristola, M., Leen, C., Jablonowska, E., Wandeler, G., Stellbrink, H., Falconer, K., D'Arminio Monforte, A., Horban, A., Rockstroh, J. K., Lundgren, J. D., Mocroft, A., Losso, M., Kundro, M., Schmied, B., Zangerle, R., Karpov, I., Vassilenko, A., Mitsura, V. M., Paduto, D., Clumeck, N., De Wit, S., Delforge, M., Florence, E., Vandekerckhove, L., Hadziosmanovic, V., Begovac, J., Machala, L., Jilich, D., Sedlacek, D., Kronborg, G., Benfield, T., Katzenstein, T., Pedersen, C., Johansen, I. S., Ostergaard, L., Wiese, L., Moller, N. F., Nielsen, L. N., Zilmer, K., Smidt, Jelena, Aho, I., Girard, P. -M., Pradier, C., Fontas, E., Duvivier, C., Behrens, G., Degen, O., Stefan, C., Bogner, J., Fätkenheuer, G., Chkhartishvili, N., Gargalianos, P., Xylomenos, G., Armenis, K., Sambatakou, H., Szlávik, J., Gottfredsson, M., Mulcahy, F., Yust, I., Turner, D., Burke, M., Shahar, E., Hassoun, G., Elinav, H., Haouzi, M., Elbirt, D., Sthoeger, Z. M., Esposito, R., Mazeu, I., Mussini, C., Mazzotta, F., Gabbuti, A., Vullo, V., Lichtner, M., Zaccarelli, M., Antinori, A., Acinapura, R., Plazzi, M., Lazzarin, A., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., Rozentale, B., Uzdaviniene, V., Matulionyte, R., Staub, T., Hemmer, R., Reiss, P., Reikvam, D. H., Maeland, A., Bruun, J., Knysz, B., Gasiorowski, J., Inglot, M., Bakowska, E., Grzeszczuk, A., Parczewski, M., Maciejewska, K., Aksak-Was, B., Beniowski, M., Mularska, E., Smiatacz, T., Gensing, M., Kamerys, J., Wojcik, K., Mozer-Lisewska, I., Caldeira, L., Mansinho, K., Maltez, F., Radoi, R., Oprea, C., Panteleev, A., Panteleev, O., Trofimora, T., Khromova, I., Kuzovatova, E., Borodulina, E., Vdoushkina, E., Jevtovic, D., Tomazic, J., Miro, J. M., Laguno, M., Martinez, E., Garcia, F., Blanco, J. L., Martinez-Rebollar, M., Mallolas, J., Moreno, S., Rodriguez, J. M., Clotet, B., Jou, A., Paredes, R., Tural, C., Puig, J., Bravo, I., Gutierrez, M., Mateo, G., Sambeat, M. A., Laporte, J. M., Sonnerborg, A., Treutiger, C. J., Flamholc, L., Weber, R., Cavassini, M., Calmy, A., Furrer, H., Battegay, M., Schmid, P., Kuznetsova, A., Kyselyova, G., Gazzard, B., Johnson, A. M., Simons, E., Edwards, S., Phillips, A., Johnson, M. A., Orkin, C., Weber, J., Scullard, G., Clarke, A., Rasmussen, L. D., Svedhem, V., Kowalska, J. D., Guaraldi, G., Kirk, O., Bojesen, A., Raben, D., Kristensen, D., Laut, K., Larsen, J. F., Podlekareva, D., Nykjær, B., Cozzi-Lepri, A., Pelchen-Matthews, A., Clinicum, HUS Inflammation Center, Infektiosairauksien yksikkö, Department of Medicine, and HUS Internal Medicine and Rehabilitation

Subjects
0301 basic medicine, Male, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Virological response, 0302 clinical medicine, continuum of care, Europe, HIV/HCV coinfection, sustained virological response, treatment, Adult, Antiviral Agents, Continuity of Patient Care, Female, Hepatitis C, Humans, Middle Aged, Young Adult, INFECTION, Pharmacology (medical), 030212 general & internal medicine, Continuum of care, Antiviral Agents/therapeutic use, biology, Health Policy, DEATH, virus diseases, Continuity of Patient Care/standards, ERA, 3. Good health, Infectious Diseases, Antibody, INTERFERON, Hepatitis C virus, HIV Infections/drug therapy, Infectious Disease, 03 medical and health sciences, Hepatitis C/drug therapy, PEOPLE, medicine, RATES, business.industry, HIV, medicine.disease, 030112 virology, Virology, digestive system diseases, 3121 General medicine, internal medicine and other clinical medicine, biology.protein, Hcv treatment, business
Abstract

Objectives: The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)-coinfected individuals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct-acting antiviral (DAA) therapy. Methods: Stages included in the continuum were as follows: anti-HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow-up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow-up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24weeks after stopping treatment. Results: Numbers and percentages for the stages of the HCV continuum of care were as follows: anti-HCV positive (n=5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n=3876), initiated HCV treatment (1693 of 3876; 43.7%), completed HCV treatment (1598 of 3876; 41.2%), follow-up HCV RNA test to allow SVR assessment (1195 of 3876; 30.8%), and cure (629 of 3876; 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P&nbsp

Published
2019
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7. Long‐term effectiveness of recommended boosted protease inhibitor‐based antiretroviral therapy in Europe

Author

Santos, J. R., Cozzi-Lepri, A., Phillips, A., De Wit, S., Pedersen, C., Reiss, P., Blaxhult, A., Lazzarin, A., Sluzhynska, M., Orkin, C., Duvivier, C., Bogner, J., Gargalianos-Kakolyris, P., Schmid, P., Hassoun, G., Khromova, I., Beniowski, M., Hadziosmanovic, V., Sedlacek, D., Paredes, R., Lundgren, J. D., Losso, M., Kundro, M., Schmied, B., Zangerle, R., Karpov, I., Vassilenko, A., Mitsura, V. M., Paduto, D., Clumeck, N., Delforge, M., Florence, E., Vandekerckhove, L., Begovac, J., Machala, L., Jilich, D., Kronborg, G., Benfield, T., Gerstoft, J., Katzenstein, T., Moller, N. F., Ostergaard, L., Wiese, L., Nielsen, L. N., Zilmer, K., Smidt, J., Ristola, M., Aho, I., Viard, J. -P., Girard, P. -M., Pradier, C., Fontas, E., Rockstroh, J., Schmidt, R., Degen, O., Stellbrink, H. J., Stefan, C., Fatkenheuer, G., Chkhartishvili, N., Gargalianos, P., Xylomenos, G., Lourida, P., Sambatakou, H., Szlavik, J., Gottfredsson, M., Mulcahy, F., Yust, I., Turner, D., Burke, M., Shahar, E., Elinav, H., Haouzi, M., Elbirt, D., Sthoeger, Z. M., D'Arminio Monforte, A., Esposito, R., Mazeu, I., Mussini, C., Mazzotta, F., Gabbuti, A., Vullo, V., Lichtner, M., Zaccarelli, M., Antinori, A., Acinapura, R., Plazzi, M., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., Rozentale, B., Uzdaviniene, V., Matulionyte, R., Staub, T., Hemmer, R., Ormaasen, V., Maeland, A., Bruun, J., Knysz, B., Gasiorowski, J., Inglot, M., Horban, A., Bakowska, E., Flisiak, R., Grzeszczuk, A., Parczewski, M., Pynka, M., Maciejewska, K., Mularska, E., Smiatacz, T., Gensing, M., Jablonowska, E., Malolepsza, E., Wojcik, K., Mozer-Lisewska, I., Caldeira, L., Mansinho, K., Maltez, F., Radoi, R., Panteleev, A., Panteleev, O., Yakovlev, A., Trofimora, T., Kuzovatova, E., Borodulina, E., Vdoushkina, E., Jevtovic, D., Tomazic, J., Gatell, J. M., Miro, J. M., Moreno, S., Rodriguez, J. M., Clotet, B., Jou, A., Tural, C., Puig, J., Bravo, I., Domingo, P., Gutierrez, M., Mateo, G., Sambeat, M. A., Laporte, J. M., Falconer, K., Thalme, A., Sonnerborg, A., Flamholc, L., Scherrer, A., Weber, R., Cavassini, M., Calmy, A., Furrer, H., Battegay, M., Kuznetsova, A., Kyselyova, G., Gazzard, B., Johnson, A. M., Simons, E., Edwards, S., Johnson, M. A., Mocroft, A., Weber, J., Scullard, G., Clarke, A., Leen, C., Gatell, J., Ledergerber, B., Kirk, O., Peters, L., Matthews, C., Fischer, A. H., Bojesen, A., Raben, D., Kristensen, D., Gronborg Laut, K., Larsen, J. F., Podlekareva, D., Shepherd, L., Schultze, A., Thiebaut, R., Burger, D., Santos, J. R., Cozzi-Lepri, A., Phillips, A., De Wit, S., Pedersen, C., Reiss, P., Blaxhult, A., Lazzarin, A., Sluzhynska, M., Orkin, C., Duvivier, C., Bogner, J., Gargalianos-Kakolyris, P., Schmid, P., Hassoun, G., Khromova, I., Beniowski, M., Hadziosmanovic, V., Sedlacek, D., Paredes, R., Lundgren, J. D., Castagna, A, on behalf of the EuroSIDA study, Group, AII - Infectious diseases, APH - Aging & Later Life, Infectious diseases, Global Health, and Amsterdam institute for Infection and Immunity

Subjects
Male, 0301 basic medicine, antiretroviral therapy-naïve patients, Lopinavir/ritonavir, darunavir, HIV Infections, Antiretroviral therapy-experienced patient, Gastroenterology, antiretroviral therapy-experienced patients, 0302 clinical medicine, atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir, Adult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Europe, Female, Humans, Middle Aged, Prospective Studies, Treatment Outcome, Pharmacology (medical), 030212 general & internal medicine, atazanavir, Antiretroviral therapy-naïve patient, Health Policy, Lopinavir, Antiretroviral Therapy, Highly Active/methods, ritonavir, Infectious Diseases, Viral load, medicine.drug, medicine.medical_specialty, HIV Infections/drug therapy, Infectious Disease, antiretroviral therapy-naive patients, 03 medical and health sciences, Internal medicine, medicine, Protease inhibitor (pharmacology), Darunavir, business.industry, 030112 virology, Atazanavir, lopinavir, Regimen, Anti-HIV Agents/therapeutic use, Ritonavir, business
Abstract

OBJECTIVES: The aim of the study was to evaluate the long-term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)-, darunavir/ritonavir (DRV/r)-, and lopinavir/ritonavir (LPV/r)-containing regimens.METHODS: Data were analysed for 5678 EuroSIDA-enrolled patients starting a DRV/r-, ATZ/r- or LPV/r-containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART-naïve subjects (8%) at ritonavir-boosted protease inhibitor (PI/r) initiation; (2) ART-experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV-1 RNA copies/mL; and (3) ART-experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL. Virological failure (VF) was defined as two consecutive VL measurements >200 copies/mL ≥24 weeks after PI/r initiation. Kaplan-Meier and multivariable Cox models were used to compare risks of failure by PI/r-based regimen. The main analysis was performed with intention-to-treat (ITT) ignoring treatment switches.RESULTS: The time to VF favoured DRV/r over ATZ/r, and both were superior to LPV/r (log-rank test; P < 0.02) in all analyses. Nevertheless, the risk of VF in ART-naïve patients was similar regardless of the PI/r initiated after controlling for potential confounders. The risk of VF in both treatment-experienced groups was lower for DRV/r than for ATZ/r, which, in turn, was lower than for LPV/r-based ART.CONCLUSIONS: Although confounding by indication and calendar year cannot be completely ruled out, in ART-experienced subjects the long-term effectiveness of DRV/r-containing regimens appears to be greater than that of ATZ/r and LPV/r.

Published
2018
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8. Incidence of cancer and overall risk of mortality in individuals treated with raltegravir-based and non-raltegravir-based combination antiretroviral therapy regimens

Author

Cozzi-Lepri, A., Zangerle, R., Machala, L., Zilmer, K., Ristola, M., Pradier, C., Kirk, O., Sambatakou, H., Fatkenheuer, G., Yust, I., Schmid, P., Gottfredsson, M., Khromova, I., Jilich, D., Flisiak, R., Smidt, J., Rozentale, B., Radoi, R., Losso, M. H., Lundgren, J. D., Mocroft, A., Kundro, M., Schmied, B., Karpov, I., Vassilenko, A., Mitsura, V. M., Paduto, D., Clumeck, N., De Wit, S., Delforge, M., Florence, E., Vandekerckhove, L., Hadziosmanovic, V., Begovac, J., Sedlacek, D., Kronborg, G., Benfield, T., Gerstoft, J., Katzenstein, T., Moller, N. F., Pedersen, C., Ostergaard, L., Wiese, L., Nielsen, L. N., Aho, I., Viard, J. -P., Girard, P. -M., Fontas, E., Duvivier, C., Rockstroh, J., Schmidt, R., Degen, O., Stellbrink, H. J., Stefan, C., Bogner, J., Chkhartishvili, N., Gargalianos, P., Xylomenos, G., Lourida, P., Szlavik, J., Mulcahy, F., Turner, D., Burke, M., Shahar, E., Hassoun, G., Elinav, H., Haouzi, M., Elbirt, D., Sthoeger, Z. M., D'Arminio Monforte, A., Esposito, R., Mazeu, I., Mussini, C., Mazzotta, F., Gabbuti, A., Vullo, V., Lichtner, M., Zaccarelli, M., Antinori, A., Acinapura, R., Plazzi, M., Lazzarin, A., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., Uzdaviniene, V., Matulionyte, R., Staub, T., Hemmer, R., Reiss, P., Ormaasen, V., Maeland, A., Bruun, J., Knysz, B., Gasiorowski, J., Inglot, M., Horban, A., Bakowska, E., Grzeszczuk, A., Parczewski, M., Maciejewska, K., Aksak-Was, B., Beniowski, M., Mularska, E., Smiatacz, T., Gensing, M., Jablonowska, E., Malolepsza, E., Wojcik, K., Mozer-Lisewska, I., Caldeira, L., Mansinho, K., Maltez, F., Oprea, C., Panteleev, A., Panteleev, O., Yakovlev, A., Trofimora, T., Kuzovatova, E., Borodulina, E., Vdoushkina, E., Jevtovic, D., Tomazic, J., Gatell, J. M., Miro, J. M., Moreno, S., Rodriguez, J. M., Clotet, B., Jou, A., Paredes, R., Tural, C., Puig, J., Bravo, I., Domingo, P., Gutierrez, M., Mateo, G., Sambeat, M. A., Laporte, J. M., Falconer, K., Thalme, A., Sonnerborg, A., Blaxhult, A., Flamholc, L., Scherrer, A., Weber, R., Cavassini, M., Calmy, A., Furrer, H., Battegay, M., Kuznetsova, A., Kyselyova, G., Sluzhynska, M., Gazzard, B., Johnson, A. M., Simons, E., Edwards, S., Phillips, A., Johnson, M. A., Orkin, C., Weber, J., Scullard, G., Clarke, A., Leen, C., Thiebaut, R., Burger, D., Peters, L., Matthews, C., Fischer, A. H., Bojesen, A., Raben, D., Kristensen, D., Gronborg Laut, K., Larsen, J. F., Podlekareva, D., Shepherd, L., Schultze, A., Amele, S., Cozzi-lepri, A, Zangerle, R, Machala, L, Zilmer, K, Ristola, M, Pradier, C, Kirk, O, Sambatakou, H, Fätkenheuer, G, Yust, I, Schmid, P, Gottfredsson, M, Khromova, I, Jilich, D, Flisiak, R, Smidt, J, Rozentale, B, Radoi, R, Losso, M. H, Lundgren, J. D, Mocroft, A, Eurosida Study, Group, Castagna, A, Lazzarin, A, AII - Infectious diseases, APH - Aging & Later Life, Infectious diseases, Global Health, Amsterdam institute for Infection and Immunity, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Clinicum, Department of Medicine, and HUS Inflammation Center

Subjects
Male, 0301 basic medicine, observational treatment comparison, HIV Infections, Rate ratio, propensity scores, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Neoplasms, Medicine and Health Sciences, Risk of mortality, AIDS-DEFINING, Pharmacology (medical), Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Original Research, EXPERIENCED, ddc:616, IMMUNODEFICIENCY, Incidence, Health Policy, Incidence (epidemiology), risk of cancer, Middle Aged, 3. Good health, Infectious Diseases, Anti-Retroviral Agents, SAFETY, EXPERIENCED PATIENTS, Cohort, AIDS-DEFINING CANCERS, Female, Historical Cohort, medicine.drug, Adult, Alnæmi, medicine.medical_specialty, animal structures, CANCERS, HIV INTEGRASE INHIBITORS, 030106 microbiology, Antiretroviral Therapy, survival, Risk Assessment, HIV-1-INFECTED PATIENTS, MALIGNANCIES, 03 medical and health sciences, Lyf, Raltegravir Potassium, Internal medicine, PATIENTS, medicine, Humans, COHORT, Highly Active, propensity score, Krabbamein, OPTIMIZED BACKGROUND THERAPY, business.industry, observational treatment, Raltegravir, Survival Analysis, Odds ratio, INFECTED INDIVIDUALS, comparison, 3121 General medicine, internal medicine and other clinical medicine, business
Abstract

Publisher's version (útgefin grein), Objectives There are currently few data on the long‐term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. Methods The EuroSIDA cohort was divided into three groups: those starting RAL‐based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. Results The RAL cohort included 1470 individuals [with 4058 person‐years of follow‐up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non‐AIDS‐related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95–1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37–2.61). In intention‐to‐treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84–1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90–1.61) and 0.83 (95% CI 0.70–0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47–1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65–1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53–1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76–1.72 for RALvs. CONC). Conclusions We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups., EuroSIDA was supported by the European Union's Seventh Framework Programme for research, technological development and demonstration under EuroCoord grant agreement no. 260694. Current support includes unrestricted grants from Bristol‐Myers Squibb, Gilead, GlaxoSmithKline LLC, Janssen R&D, Merck and Co. Inc. and Pfizer Inc. The participation of centres from Switzerland was supported by The Swiss National Science Foundation (Grant 108787). The study is also supported by a grant (grant number DNRF126) from the Danish National Research Foundation.

Published
2017
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15. The extent of B-cell activation and dysfunction preceding lymphoma development in HIV-positive people

Author

Shepherd, L., Borges, Á. H., Harvey, R., Bower, M., Grulich, A., Silverberg, M., Weber, J., Ristola, M., Viard, J. -P., Bogner, J. R., Gargalianos-Kakolyris, P., Mussini, C., Mansinho, K., Yust, I., Paduta, D., Jilich, D., Smiatacz, T., Radoi, R., Tomazic, J., Plomgaard, P., Frikke-Schmidt, R., Lundgren, J., Mocroft, A., Losso, M., Kundro, M., Schmied, B., Karpov, I., Vassilenko, A., Mitsura, V. M., Paduto, D., Clumeck, N., De Wit, S., Delforge, M., Florence, E., Vandekerckhove, L., Hadziosmanovic, V., Begovac, J., Machala, L., Sedlacek, D., Kronborg, G., Benfield, T., Gerstoft, J., Katzenstein, T., Møller, N. F., Pedersen, C., Ostergaard, L., Wiese, L., Nielsen, L. N., Zilmer, K., Jelena, S., Nakkusosakond, S., Kohtla-Järve, Null, Aho, I., Girard, P. -M., Pradier, C., Fontas, E., Duvivier, C., Rockstroh, J., Schmidt, R., Degen, O., Stellbrink, H. J., Stefan, C., Fätkenheuer, G., Chkhartishvili, N., Gargalianos, P., Xylomenos, G., Armenis, K., Sambatakou, H., Szlávik, J., Gottfredsson, M., Mulcahy, F., Turner, D., Burke, M., Shahar, E., Hassoun, G., Elinav, H., Haouzi, M., Elbirt, D., Sthoeger, Z. M., D'Arminio Monforte, A., Esposito, R., Mazeu, I., Mazzotta, F., Gabbuti, A., Vullo, V., Lichtner, M., Zaccarelli, M., Antinori, A., Acinapura, R., Plazzi, M., Lazzarin, A., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., Sacco, Osp. L, Rozentale, B., Uzdaviniene, V., Matulionyte, R., Staub, T., Hemmer, R., Reiss, P., Ormaasen, V., Maeland, A., Bruun, J., Knysz, B., Gasiorowski, J., Inglot, M., Horban, A., Bakowska, E., Flisiak, R., Grzeszczuk, A., Parczewski, M., Maciejewska, K., Aksak-Was, B., Beniowski, M., Mularska, E., Gensing, M., Jablonowska, E., Malolepsza, E., Wojcik, K., Mozer-Lisewska, I., Caldeira, L., Maltez, F., Oprea, C., Victor, B., Panteleev, A., Panteleev, O., Yakovlev, A., Trofimora, T., Khromova, I., Kuzovatova, E., Borodulina, E., Vdoushkina, E., Jevtovic, D., Gatell, J. M., Miró, J. M., Moreno, S., Rodriguez, J. M., Clotet, B., Jou, A., Paredes, R., Tural, C., Puig, J., Bravo, I., Domingo, P., Gutierrez, M., Mateo, G., Sambeat, M. A., Laporte, J. M., Falconer, K., Thalme, A., Sonnerborg, A., Blaxhult, A., Flamholc, L., Scherrer, A., Weber, R., Cavassini, M., Calmy, A., Furrer, H., Battegay, M., Schmid, P., Kuznetsova, A., Kyselyova, G., Sluzhynska, M., Gazzard, B., Johnson, A. M., Simons, E., Edwards, S., Phillips, A., Johnson, M. A., Orkin, C., Scullard, G., Clarke, A., Leen, C., Gatell, J., d'Arminio Monforte, A., Kirk, O., Peters, L., Matthews, C., Fischer, A. H., Bojesen, A., Raben, D., Kristensen, D., Grønborg Laut, K., Larsen, J. F., Podlekareva, D., Cozzi-Lepri, A., Schultze, A., Amele, S., AII - Infectious diseases, APH - Aging & Later Life, Infectious diseases, Global Health, Amsterdam institute for Infection and Immunity, Shepherd, L., Borges, à h, Harvey, R., Bower, M., Grulich, A., Silverberg, M., Weber, J., Ristola, M., Viard, J. . P., Bogner, J. R., Gargalianos kakolyris, P., Mussini, C., Mansinho, K., Yust, I., Paduta, D., Jilich, D., Smiatacz, T., Radoi, R., Tomazic, J., Plomgaard, P., Frikke schmidt, R., Lundgren, J., Mocroft, A., Eurosida In, Eurocoord, and Castagna, Antonella

Subjects
0301 basic medicine, Male, Lymphoma, immunoglobulins, HIV Infections, Lymphocyte Activation, Immunoglobulin D, Gastroenterology, Immunoglobulin G, 0302 clinical medicine, B-cell dysfunction, biomarkers, free light chains, HIV, lymphoma, Health Policy, Infectious Diseases, Pharmacology (medical), hemic and lymphatic diseases, Medicine, Prospective Studies, Immunodeficiency, B-Lymphocytes, biology, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Cohort, Female, Adult, medicine.medical_specialty, AIDS-related lymphoma, 03 medical and health sciences, Internal medicine, Immunoglobulin, Humans, business.industry, Free light chain, Biomarker, Odds ratio, medicine.disease, Confidence interval, 030104 developmental biology, Case-Control Studies, Immunology, biology.protein, Immunoglobulin Light Chains, business
Abstract

OBJECTIVES: B-cell dysfunction and activation are thought to contribute to lymphoma development in HIV-positive people; however, the mechanisms are not well understood. We investigated levels of several markers of B-cell dysfunction [free light chain (FLC)-κ, FLC-λ, immunoglobulin G (IgG), IgA, IgM and IgD] prior to lymphoma diagnosis in HIV-positive people.METHODS: A nested matched case-control study was carried out within the EuroSIDA cohort, including 73 HIV-positive people with lymphoma and 143 HIV-positive lymphoma-free controls. Markers of B-cell dysfunction were measured in prospectively stored serial plasma samples collected before the diagnosis of lymphoma (or selection date in controls). Marker levels ≤ 2 and > 2 years prior to diagnosis were investigated.RESULTS: Two-fold higher levels of FLC-κ [odds ratio (OR) 1.84; 95% confidence interval (CI) 1.19, 2.84], FLC-λ (OR 2.15; 95% CI 1.34, 3.46), IgG (OR 3.05; 95% CI 1.41, 6.59) and IgM (OR 1.46; 95% CI 1.01, 2.11) were associated with increased risk of lymphoma > 2 years prior to diagnosis, but not ≤ 2 years prior. Despite significant associations > 2 years prior to diagnosis, the predictive accuracy of each marker was poor, with FLC-λ emerging as the strongest candidate with a c-statistic of 0.67 (95% CI 0.58, 0.76).CONCLUSIONS: FLC-κ, FLC-λ and IgG levels were higher > 2 years before lymphoma diagnosis, suggesting that B-cell dysfunction occurs many years prior to lymphoma development. However, the predictive value of each marker was low and they are unlikely candidates for risk assessment for targeted intervention.

Published
2018
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16. The Influence of Phenocrysts on Degassing in Crystal‐Bearing Magmas With Rhyolitic Groundmass Melts.

Author

deGraffenried, R. L., Larsen, J. F., Graham, N. A., and Cashman, K. V.

Subjects
*PHENOCRYSTS, *RHYOLITE, *PERMEABILITY, *DYNAMICS, *CRYSTALLIZATION
Abstract

The porosity at which a magma becomes permeable (i.e., the percolation threshold; ϕc) is important for magma degassing; it is also poorly constrained in crystal‐bearing systems. To address this, we conduct high pressure‐temperature decompression experiments on water‐saturated rhyolitic melts with variable crystal contents. We find that crystal‐bearing run products become permeable at ~55‐vol.% vesicularity (crystal free), a value that is similar to that found in decompression‐crystallization experiments using basaltic andesite compositions. Our results provide insight into controls on the eruption styles of hydrous, crystal‐bearing magmas in general and controls on pulsatory Vulcanian behavior, in particular. Plain Language Summary: Rates of gas escape from an ascending magma control volcanic eruption style. Gas transport along permeable connected bubble pathways is an important step in the degassing process as it allows pressurized gases to escape. The bubble concentration at which permeability develops (the percolation threshold) is poorly characterized in magmas with moderate to high crystallinities. In this study, we use decompression experiments with controlled crystal contents to address this knowledge gap. Our results show that the presence of at least 20‐vol.% crystals reduces the percolation threshold in crystal‐bearing magmas compared to crystal‐free magmas. This suggests that the presence of crystals will enhance gas escape during magma ascent and has implications for transitions between explosive and effusive eruption styles. Key Points: Addition of 20‐vol.% equant particles to rhyolitic magma causes a reduced percolation threshold compared to crystal‐free magmasMeasured experimental crystal‐bearing percolation thresholds agree well with values from natural Vulcanian eruption samplesReduced percolation threshold in crystal‐bearing magmas has implications for the cyclicity of Vulcanian explosions [ABSTRACT FROM AUTHOR]

Published
2019
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18. Crystal controls on permeability development and degassing in basaltic andesite magma.

Author

Lindoo, A., Larsen, J. F., Cashman, K. V., and Oppenheimer, J.

Subjects
*MAFIC rocks, *MAGMAS, *CRYSTALLIZATION, *PERMEABILITY, *ANDESITE
Abstract

Understanding degassing of mafic magmas is important for modeling eruptions and examining controls on eruption style. We conducted high-pressure-high-temperature isothermal decompression experiments to investigate the effects of decompression-induced crystallization on permeability development and magma degassing. Experiments were performed on hydrous basaltic andesite (54 wt% SiO2) decompression rates equivalent to magma ascent velocities of ~1-3 m s-1. We measured the gas flux of the quenched samples using a bench-top permeameter and calculated the Darcian (k1) and inertial (k2) permeabilities using the Forchheimer equation. The experimental samples developed permeability at a critical vesicularity (Φc) of 56.4 ± 2.7 vol% (at 0.125 MPa s-1) and 50.76 ± 5.6 vol% (at 0.083 MPa s-1), considerably lower than the Φc > 63 vol% permeability threshold determined for crystal-free basaltic andesite melts. The percolation threshold decrease is observed when the microlites comprise ≥~20 vol% and can be explained by the onset of yield strength, which occurs when the crystals form a loosely packed, touching framework. [ABSTRACT FROM AUTHOR]

Published
2017
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19. Presence of uterine pinopodes at the embryo-endometrial interface during human implantation in vitro.

Author

Bentin-Ley, U, Sjögren, A, Nilsson, L, Hamberger, L, Larsen, JF, Horn, T, and Larsen, J F

Abstract

In order to study changes occurring on the surfaces of human endometrial epithelial cells in the presence of an implanted blastocyst, we used scanning electron microscopy for investigation of five endometrial biopsies and three human implantation sites obtained in vitro. All specimens showed areas with endometrial pinopodes, separated by cells displaying microvilli or cilia at the apical surface. Pinopode formation was more pronounced in endometrial biopsies than in cell cultures. All blastocysts adhered to pinopode presenting cells. Endometrial surface changes were not seen around the blastocysts. The results of this study demonstrate that cultured endometrial epithelial cells are capable of pinopode formation. Furthermore, endometrial epithelial pinopodes, generally considered as a marker of endometrial receptivity, seem to be directly involved in the adhesion of the blastocyst to the endometrial surface. [ABSTRACT FROM AUTHOR]

Published
1999
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26. Ultrastructure of a human implantation site.

Author

Knoth, Mogens, Larsen, Jørgen Falck, Knoth, M, and Larsen, J F

Abstract

The fins structure of the trophoblast from a previllous human ovum is described. The extra-embryonal mesoderm was lined by cylotrophoblasts, which were beginning to form the primary villi. The ultrastructure of these cells was similar to that of the Langhans' cells of the definitive villus. The syncytiotrophoblast was located peripherally and consisted of a mixture of giant cells and syncytial masses. This cell type was well differentiated, with its cytoplasm occupied by large amounts of granular endoplasmic reticulum. Golgi elements, and vesicles. The syncytiotrophoblast had many microvilli and pinocytotic vesicles at the surface, lining the lacunae which contained maternal blood cells. Close contact was observed between the trophoblast and the cells of the maternal glands. The trophoblastic invasion of a maternal vessel is described, and the trophoblastic invasion is discussed. [ABSTRACT FROM AUTHOR]

Published
1972
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27. Ultrastructure of the anchoring villi and trophoblastic shell in the second week of placentation.

Author

Larsen, Jørgen Falck, Knoth, Mogens, Larsen, J F, and Knoth, M

Abstract

The fine structure of the anchoring villi and the trophoblastic shell of a human embryo with four somites is described. The ultrastructure of the cytotro-phoblast of the proximal part of the anchoring villi was similar to that of the Langhans' cells of the free villi. The distal cytotrophoblasts had irregular nuclei and contained more rough endoplasmic reticulum. The cytotrophoblasts of the base of the villi were large and contained large amounts of glycogen. The basal plate comprised a variety of trophoblastic cells. Most commonly seen was the mononuclear giant cell, which was rich in rough endoplasmic reticulum, glycogen and fibrils. In the periphery of the placental site, the trophoblasts were scattered among the maternal cells. Foetal and maternal cells were often found side by side without any reaction. However, the cell membranes of trophoblastic giant cells and those of the uterine gland cells were closely apposed and desmosomes were observed between the foetal and maternal cells. In other places cell membranes between trophoblastic cells and uterine epithelium seemed to disintegrate. [ABSTRACT FROM AUTHOR]

Published
1971
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28. Ultrastructure of a granulosa cell tumour.

Author

Pedersen, Poul Hjortkjær, Larsen, Jørgen Falck, Pedersen, P H, and Larsen, J F

Abstract

. The fine structure of a hormonal active granulosa cell tumour is described. The greater part of the tumour consisted of a cell type resembling the granulosa cell of the normal follicle. It contained many Golgi elements but was poor in smooth and rough endoplasmic reticulum. Another type of cell was found in the proximity of strands of connective tissue. The second type had large amounts of smooth endoplasmic reticulum and lipid droplets. This type is probably the thecal element and its ultrastructure indicates that it represents the endocrine active part of the tumour. [ABSTRACT FROM AUTHOR]

Published
1970
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31. Testing a present value model of forest land

Author

Larsen, J. F. and Riis, J.

Subjects
METHODOLOGY, ECONOMICS, FOREST management
Abstract

The empirical validity of a simple present value model describing forest land prices according to economic fundamentals is examined. The implications of the model are derived and tested by use of time series econometric methods on Danish rent and price data in the period 1911- -92, A necessary condition of the model is rejected by the data, probably due to an under parameterization of the model. An extension of the model, including the omitted variable, is suggested and discussed theoretically. Key words: Cointegration, land rents. [ABSTRACT FROM AUTHOR]

Published
1997
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32. Distribution of dissolved water in magmatic glass records growth and resorption of bubbles.

Author

McIntosh, I. M., Llewellin, E. W., Humphreys, M. C. S., Nichols, A. R. L., Burgisser, A., Schipper, C. I., and Larsen, J. F.

Subjects
*MAGMATISM, *BUBBLES, *VOLCANIC eruptions, *QUENCHING (Chemistry), *SPATIAL distribution (Quantum optics), *WATER distribution
Abstract

Volcanic eruptions are driven by the growth of gas bubbles in magma. Bubbles grow when dissolved volatile species, principally water, diffuse through the silicate melt and exsolve at the bubble wall. On rapid cooling, the melt quenches to glass, preserving the spatial distribution of water concentration around the bubbles (now vesicles), offering a window into pre-eruptive conditions. We measure the water distribution around vesicles in experimentally-vesiculated samples, with high spatial resolution. We find that, contrary to expectation, water concentration increases towards vesicles, indicating that water is resorbed from bubbles during cooling; textural evidence suggests that resorption occurs largely before the melt solidifies. Speciation data indicate that the molecular water distribution records resorption, whilst the hydroxyl distribution records earlier decompressive growth. Our results challenge the emerging paradigm that resorption indicates fluctuating pressure conditions, and lay the foundations for a new tool for reconstructing the eruptive history of natural volcanic products. [ABSTRACT FROM AUTHOR]

Published
2014
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