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25 results on '"Mikiashvili L."'

1. Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB:HIV study

Author

Karpov, I., Vassilenko, A., Skrahina, A., Klimuk, D., Skrahin, A., Kondratenko, O., Zalutskaya, A., Bondarenko, V., Mitsura, V., Kozorez, E., Tumash, O., Suetnov, O., Paduto, D., Iljina, V., Kummik, T., Bolokadze, N., Mshvidobadze, K., Lanchava, N., Goginashvili, L., Mikiashvili, L., Bablishvili, N., Rozentale, B., Zeltina, I., Janushkevich, I., Caplinskiene, I., Caplinskas, S., Kancauskiene, Z., Podlasin, R., Wiercinska-Drapalo, A., Thompson, M., Kozlowska, J., Grezesczuk, A., Bura, M., Knysz, B., Inglot, M., Garlicki, A., Loster, J., Tetradov, S., Duiculescu, D., Rakhmanova, A., Panteleeva, O., Yakovlev, A., Kozlov, A., Tyukalova, A., Vlasova, Y., Panteleev, A., Trofimov, T., Kyselyova, G., Andersen, A.B., Thorsteinsson, K., Payen, M.C., Kabeya, K., Necsoi, C., Dabis, F., Bruyand, M., Morlat, P., Dupont, A., Gerard, Y., Bonnal, F., Ceccaldi, J., De Witte, S., Monlun, E., Lataste, P., Chossat, I., Miller, R., Vora, N., Cooke, G., Mullaney, S., Wilkins, E., George, V., Collini, P., Dockrell, D., Post, F., Campbell, L., Brum, R., Mabonga, E., Saigal, P., Kegg, S., Ainsworth, J., Waters, A., Dhar, J., Mashonganyika, L., Girardi, E., Rianda, A., Galati, V., Pinnetti, C., Tommasi, C., Lapadula, G., Di Biagio, A., Parisini, A., Carbonara, S., Angarano, G., Purgatorio, M., Matteelli, A., Apostoli, A., Toibaro, J., Macias, L. Moreno, Warley, E., Tavella, S., Garcia Messina, O., Gear, O., Laplume, H., Marson, C., Contarelia, J., Michaan, M., Scapellato, P., Alessandro, D.D., Bartoletti, B., Palmero, D., Elias, C., Cortes, C., Crabtree, B., Mosqueda Gomez, J.L., Villanueva, A., Gonzalez Hernandez, L.A., Efsen, A.M.W., Schultze, A., Miller, R.F., Podlekareva, D.N., Miro, J.M., Furrer, H., Losso, M.H., Caylà, J.A., Mocroft, A., Lundgren, J.D., Post, F.A., and Kirk, O.

Published
2018
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3. Impact of Prior Tuberculosis Treatment With New/Companion Drugs on Clinical Outcomes in Patients Receiving Concomitant Bedaquiline and Delamanid for Multidrug- and Rifampicin-Resistant Tuberculosis.

Author

Mikiashvili, L, Kempker, R R, Chakhaia, T S, Bablishvili, N, Avaliani, Z, Lomtadze, N, Schechter, M C, and Kipiani, M

Subjects
*DRUG therapy for tuberculosis, *COMBINATION drug therapy, *RESEARCH funding, *PATIENT safety, *QUESTIONNAIRES, *RETROSPECTIVE studies, *DESCRIPTIVE statistics, *ANTITUBERCULAR agents, *LONGITUDINAL method, *DRUG efficacy, *RIFAMPIN, *DRUG resistance
Abstract

Background There are scarce data on the clinical outcomes of persons retreated with new/companion anti-tuberculosis (TB) drugs for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). We sought to evaluate the efficacy and safety of bedaquiline and delamanid containing regimens among patients with and without prior exposure to the new/companion drugs (bedaquiline, delamanid, linezolid, clofazimine, and fluoroquinolones). Methods We conducted a retrospective cohort study among patients with pulmonary MDR/RR-TB in Georgia who received bedaquiline and delamanid combination as a part of a salvage regimen from November 2017 to December 2020 in a programmatic setting. Results Among 106 persons with a median age of 39.5 years, 44 (41.5%) were previously treated with new/companion TB drugs. Patients with prior exposure to new/companion drugs had higher rates of baseline resistance compared to those without exposure to new/companion TB drugs (bedaquiline 15.2% vs 1.8%, linezolid 22.2% vs 16.7%). Sputum culture conversion rates among patients exposed and not exposed to new/companion drugs were 65.9% vs 98.0%, respectively (P <.001). Among patients with and without prior new/companion TB drug use, favorable outcome rates were 41.0% and 82.3%, respectively (P <.001). Treatment adherence in 32 (30.2%) patients was ≤80%. Five of 21 patients (23.8%) who had a baseline and repeat susceptibility test had acquired bedaquiline resistance. QTC/F prolongation (>500 ms) was rare (2.8%). Conclusions Prior exposure to new/companion TB drugs was associated with poor clinical outcomes and acquired drug resistance. Tailoring the TB regimen to each patient's drug susceptibility test results and burden of disease and enhancing adherence support may improve outcomes. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Healthcare delivery for HIV-positive people with tuberculosis in Europe

Author

Bentzon, A, Panteleev, A, Mitsura, V, Borodulina, E, Skrahina, A, Denisova, E, Tetradov, S, Podlasin, R, Riekstina, V, Kancauskiene, Z, Paduto, D, Mocroft, A, Trofimova, T, Miller, R, Post, F, Grezesczuk, A, Lundgren, J, Inglot, M, Podlekareva, D, Bolokadze, N, Kirk, O, Karpov, I, Vassilenko, A, Klimuk, D, Skrahin, A, Kondratenko, O, Zalutskaya, A, Bondarenko, V, Kozorez, E, Tumash, O, Suetnov, O, Iljina, V, Kummik, T, Mshvidobadze, K, Lanchava, N, Goginashvili, L, Mikiashvili, L, Bablishvili, N, Rozentale, B, Zeltina, I, Janushkevich, I, Caplinskiene, I, Caplinskas, S, Wiercinska-Drapalo, A, Thompson, M, Kozlowska, J, Bura, M, Knysz, B, Garlicki, A, Loster, J, Duiculescu, D, Rakhmanova, A, Panteleeva, O, Yakovlev, A, Kozlov, A, Tyukalova, A, Vlasova, Y, Trofimov, T, Kyselyova, G, Obel, N, Gerstoft, J, Kronborg, G, Payen, M, Kabeya, K, Necsoi, C, Dabis, F, Tsaranazy, A, Cazanave, C, Furrer, H, Sagette, M, Rickenbach, M, Elzi, L, Battegay, M, Sculier, D, Calmy, A, Cavassini, M, Bruno, A, Bernasconi, E, Hoffmann, M, Vernazza, P, Fehr, J, Weber, R, Vora, N, Cooke, G, Mullaney, S, Wilkins, E, George, V, Collini, P, Dockrell, D, Campbell, L, Brum, R, Mabonga, E, Saigal, P, Kegg, S, Ainsworth, J, Waters, A, Dhar, J, Ellis, K, Spallanzani, O, Girardi, E, Rianda, A, Galati, V, Pinnetti, C, Tommasi, C, San Gerardo, A, Lapadula, G, Di Biagio, A, Parisini, A, Carbonara, S, Angarano, G, Purgatorio, M, Matteelli, A, Apostoli, A, Miro, J, Manzardo, C, Ligero, C, Gonzalez, J, Martinez-Martinez, J, Sanchez, F, Knobel, H, Salvado, M, Lopez-Colomes, J, Martinez-Lacasa, X, Cuchi, E, Falco, V, Curran, A, Tortola, M, Ocana, I, Vidal, R, Sambeat, M, Pomar, V, Coll, P, Pozamczer, D, Saumoy, M, Alcaide, F, Cayla, J, Moreno, A, Millet, J, Orcau, A, Fina, L, Romero, A, Roldan, L, Iribarren, J, Ibarguren, M, Moreno, S, Gonzalez, A, Miralles, P, Aldamiz-Echevarria, T, Losso, M, Toibaro, J, Gambardella, L, Ramos Mejia, J, Moreno Macias, L, Warley, E, Tavella, S, Garcia Messina, O, Gear, O, Laplume, H, Marson, C, Contarelia, J, Michaan, M, Scapellato, P, Bartoletti, B, Palmero, D, Elias, C, Cortes, C, Crabtree, B, Mosqueda Gomez, J, Villanueva, J, Gonzalez Hernandez, L, Badial, F, Bentzon A. K., Panteleev A., Mitsura V., Borodulina E., Skrahina A., Denisova E., Tetradov S., Podlasin R., Riekstina V., Kancauskiene Z., Paduto D., Mocroft A., Trofimova T., Miller R., Post F., Grezesczuk A., Lundgren J. D., Inglot M., Podlekareva D., Bolokadze N., Kirk O., Karpov I., Vassilenko A., Klimuk D., Skrahin A., Kondratenko O., Zalutskaya A., Bondarenko V., Kozorez E., Tumash O., Suetnov O., Iljina V., Kummik T., Mshvidobadze K., Lanchava N., Goginashvili L., Mikiashvili L., Bablishvili N., Rozentale B., Zeltina I., Janushkevich I., Caplinskiene I., Caplinskas S., Wiercinska-Drapalo A., Thompson M., Kozlowska J., Bura M., Knysz B., Garlicki A., Loster J., Duiculescu D., Rakhmanova A., Panteleeva O., Yakovlev A., Kozlov A., Tyukalova A., Vlasova Y., Trofimov T., Kyselyova G., Obel N., Gerstoft J., Kronborg G., Payen M. C., Kabeya K., Necsoi C., Dabis F., Tsaranazy A., Cazanave C., Furrer H., Sagette M., Rickenbach M., Elzi L., Battegay M., Sculier D., Calmy A., Cavassini M., Bruno A., Bernasconi E., Hoffmann M., Vernazza P., Fehr J., Weber R., Vora N., Cooke G., Mullaney S., Wilkins E., George V., Collini P., Dockrell D., Campbell L., Brum R., Mabonga E., Saigal P., Kegg S., Ainsworth J., Waters A., Dhar J., Ellis K., Spallanzani O. L., Girardi E., Rianda A., Galati V., Pinnetti C., Tommasi C., San Gerardo A. O., Lapadula G., Di Biagio A., Parisini A., Carbonara S., Angarano G., Purgatorio M., Matteelli A., Apostoli A., Miro J. M., Manzardo C., Ligero C., Gonzalez J., Martinez-Martinez J. A., Sanchez F., Knobel H., Salvado M., Lopez-Colomes J. L., Martinez-Lacasa X., Cuchi E., Falco V., Curran A., Tortola M. T., Ocana I., Vidal R., Sambeat M. A., Pomar V., Coll P., Pozamczer D., Saumoy M., Alcaide F., Cayla J., Moreno A., Millet J. P., Orcau A., Fina L., Romero A., Roldan L. L., Iribarren J. A., Ibarguren M., Moreno S., Gonzalez A., Miralles P., Aldamiz-Echevarria T., Losso M., Toibaro J., Gambardella L., Ramos Mejia J. M., Moreno Macias L., Warley E., Tavella S., Garcia Messina O., Gear O., Laplume H., Marson C., Contarelia J., Michaan M., Scapellato P., Bartoletti B., Palmero D., Elias C., Cortes C., Crabtree B., Mosqueda Gomez J. L., Villanueva J. A., Gonzalez Hernandez L. A., Badial F., Bentzon, A, Panteleev, A, Mitsura, V, Borodulina, E, Skrahina, A, Denisova, E, Tetradov, S, Podlasin, R, Riekstina, V, Kancauskiene, Z, Paduto, D, Mocroft, A, Trofimova, T, Miller, R, Post, F, Grezesczuk, A, Lundgren, J, Inglot, M, Podlekareva, D, Bolokadze, N, Kirk, O, Karpov, I, Vassilenko, A, Klimuk, D, Skrahin, A, Kondratenko, O, Zalutskaya, A, Bondarenko, V, Kozorez, E, Tumash, O, Suetnov, O, Iljina, V, Kummik, T, Mshvidobadze, K, Lanchava, N, Goginashvili, L, Mikiashvili, L, Bablishvili, N, Rozentale, B, Zeltina, I, Janushkevich, I, Caplinskiene, I, Caplinskas, S, Wiercinska-Drapalo, A, Thompson, M, Kozlowska, J, Bura, M, Knysz, B, Garlicki, A, Loster, J, Duiculescu, D, Rakhmanova, A, Panteleeva, O, Yakovlev, A, Kozlov, A, Tyukalova, A, Vlasova, Y, Trofimov, T, Kyselyova, G, Obel, N, Gerstoft, J, Kronborg, G, Payen, M, Kabeya, K, Necsoi, C, Dabis, F, Tsaranazy, A, Cazanave, C, Furrer, H, Sagette, M, Rickenbach, M, Elzi, L, Battegay, M, Sculier, D, Calmy, A, Cavassini, M, Bruno, A, Bernasconi, E, Hoffmann, M, Vernazza, P, Fehr, J, Weber, R, Vora, N, Cooke, G, Mullaney, S, Wilkins, E, George, V, Collini, P, Dockrell, D, Campbell, L, Brum, R, Mabonga, E, Saigal, P, Kegg, S, Ainsworth, J, Waters, A, Dhar, J, Ellis, K, Spallanzani, O, Girardi, E, Rianda, A, Galati, V, Pinnetti, C, Tommasi, C, San Gerardo, A, Lapadula, G, Di Biagio, A, Parisini, A, Carbonara, S, Angarano, G, Purgatorio, M, Matteelli, A, Apostoli, A, Miro, J, Manzardo, C, Ligero, C, Gonzalez, J, Martinez-Martinez, J, Sanchez, F, Knobel, H, Salvado, M, Lopez-Colomes, J, Martinez-Lacasa, X, Cuchi, E, Falco, V, Curran, A, Tortola, M, Ocana, I, Vidal, R, Sambeat, M, Pomar, V, Coll, P, Pozamczer, D, Saumoy, M, Alcaide, F, Cayla, J, Moreno, A, Millet, J, Orcau, A, Fina, L, Romero, A, Roldan, L, Iribarren, J, Ibarguren, M, Moreno, S, Gonzalez, A, Miralles, P, Aldamiz-Echevarria, T, Losso, M, Toibaro, J, Gambardella, L, Ramos Mejia, J, Moreno Macias, L, Warley, E, Tavella, S, Garcia Messina, O, Gear, O, Laplume, H, Marson, C, Contarelia, J, Michaan, M, Scapellato, P, Bartoletti, B, Palmero, D, Elias, C, Cortes, C, Crabtree, B, Mosqueda Gomez, J, Villanueva, J, Gonzalez Hernandez, L, Badial, F, Bentzon A. K., Panteleev A., Mitsura V., Borodulina E., Skrahina A., Denisova E., Tetradov S., Podlasin R., Riekstina V., Kancauskiene Z., Paduto D., Mocroft A., Trofimova T., Miller R., Post F., Grezesczuk A., Lundgren J. D., Inglot M., Podlekareva D., Bolokadze N., Kirk O., Karpov I., Vassilenko A., Klimuk D., Skrahin A., Kondratenko O., Zalutskaya A., Bondarenko V., Kozorez E., Tumash O., Suetnov O., Iljina V., Kummik T., Mshvidobadze K., Lanchava N., Goginashvili L., Mikiashvili L., Bablishvili N., Rozentale B., Zeltina I., Janushkevich I., Caplinskiene I., Caplinskas S., Wiercinska-Drapalo A., Thompson M., Kozlowska J., Bura M., Knysz B., Garlicki A., Loster J., Duiculescu D., Rakhmanova A., Panteleeva O., Yakovlev A., Kozlov A., Tyukalova A., Vlasova Y., Trofimov T., Kyselyova G., Obel N., Gerstoft J., Kronborg G., Payen M. C., Kabeya K., Necsoi C., Dabis F., Tsaranazy A., Cazanave C., Furrer H., Sagette M., Rickenbach M., Elzi L., Battegay M., Sculier D., Calmy A., Cavassini M., Bruno A., Bernasconi E., Hoffmann M., Vernazza P., Fehr J., Weber R., Vora N., Cooke G., Mullaney S., Wilkins E., George V., Collini P., Dockrell D., Campbell L., Brum R., Mabonga E., Saigal P., Kegg S., Ainsworth J., Waters A., Dhar J., Ellis K., Spallanzani O. L., Girardi E., Rianda A., Galati V., Pinnetti C., Tommasi C., San Gerardo A. O., Lapadula G., Di Biagio A., Parisini A., Carbonara S., Angarano G., Purgatorio M., Matteelli A., Apostoli A., Miro J. M., Manzardo C., Ligero C., Gonzalez J., Martinez-Martinez J. A., Sanchez F., Knobel H., Salvado M., Lopez-Colomes J. L., Martinez-Lacasa X., Cuchi E., Falco V., Curran A., Tortola M. T., Ocana I., Vidal R., Sambeat M. A., Pomar V., Coll P., Pozamczer D., Saumoy M., Alcaide F., Cayla J., Moreno A., Millet J. P., Orcau A., Fina L., Romero A., Roldan L. L., Iribarren J. A., Ibarguren M., Moreno S., Gonzalez A., Miralles P., Aldamiz-Echevarria T., Losso M., Toibaro J., Gambardella L., Ramos Mejia J. M., Moreno Macias L., Warley E., Tavella S., Garcia Messina O., Gear O., Laplume H., Marson C., Contarelia J., Michaan M., Scapellato P., Bartoletti B., Palmero D., Elias C., Cortes C., Crabtree B., Mosqueda Gomez J. L., Villanueva J. A., Gonzalez Hernandez L. A., and Badial F.

Abstract

Background: In a 2013 survey, we reported distinct discrepancies in delivery of tuberculosis (TB) and HIV services in eastern Europe (EE) vs. western Europe (WE). Objectives: To verify the differences in TB and HIV services in EE vs. WE. Methods: Twenty-three sites completed a survey in 2018 (EE, 14; WE, nine; 88% response rate). Results were compared across as well as within the two regions. When possible, results were compared with the 2013 survey. Results: Delivery of healthcare was significantly less integrated in EE: provision of TB and HIV services at one site (36% in EE vs. 89% in WE; P = 0.034), and continued TB follow-up in one location (42% vs. 100%; P = 0.007). Although access to TB diagnostics, standard TB and HIV drugs was generally good, fewer sites in EE reported unlimited access to rifabutin/multi-drug-resistant TB (MDR-TB) drugs, HIV integrase inhibitors and opioid substitution therapy (OST). Compared with 2013, routine usage of GeneXpert was more common in EE in 2018 (54% vs. 92%; P = 0.073), as was access to moxifloxacin (46% vs. 91%; P = 0.033), linezolid (31% vs. 64%; P = 0.217), and bedaquiline (0% vs. 25%; P = 0.217). Integration of TB and HIV services (46% vs. 39%; P = 1.000) and provision of OST to patients with opioid dependency (54% vs. 46%; P = 0.695) remained unchanged. Conclusion: Delivery of TB and HIV healthcare, including integration of TB and HIV care and access to MDR-TB drugs, still differs between WE and EE, as well as between individual EE sites.

Published
2021

5. Delayed diagnosis of tuberculosis in persons living with HIV in Eastern Europe: associated factors and effect on mortality—a multicentre prospective cohort study

Author

Kraef, C, Bentzon, A, Panteleev, A, Skrahina, A, Bolokadze, N, Tetradov, S, Podlasin, R, Karpov, I, Borodulina, E, Denisova, E, Azina, I, Lundgren, J, Johansen, I, Mocroft, A, Podlekareva, D, Kirk, O, Vassilenko, A, Klimuk, D, Kondratenko, O, Zalutskaya, A, Bondarenko, V, Mitsura, V, Kozorez, E, Tumash, O, Suetnov, O, Paduto, D, Iljina, V, Kummik, T, Mshvidobadze, K, Lanchava, N, Goginashvili, L, Mikiashvili, L, Bablishvili, N, Rozentale, B, Zeltina, I, Janushkevich, I, Caplinskiene, I, Caplinskas, S, Kancauskiene, Z, Wiercinska-Drapalo, A, Thompson, M, Kozlowska, J, Grezesczuk, A, Bura, M, Knysz, B, Inglot, M, Garlicki, A, Loster, J, Uiculescu, D, Rakhmanova, A, Panteleev, O, Yakovlev, A, Kozlov, A, Tyukalova, A, Vlasova, Y, Rofimov, T, Kyselyova, G, Obel, N, Gerstoft, J, Kronborg, G, Payen, M, Abeya, K, Necsoi, C, Dabis, F, Tsaranazy, A, Cazanave, C, Furrer, H, Sagette, M, Rickenbach, M, Sculier, D, Calmy, A, Cavassini, M, Bruno, A, Bernasconi, E, Hoffmann, M, Vernazza, P, Fehr, J, Weber, R, Miller, R, Vora, N, Cooke, G, Mullaney, S, Wilkins, E, George, V, Collini, P, Dockrell, D, Post, F, Campbell, L, Brum, R, Mabonga, E, Saigal, P, Kegg, S, Ainsworth, J, Waters, A, Dhar, J, Ellis, K, Girardi, E, Rianda, A, Galati, V, Pinnetti, C, Tommasi, C, Lapadula, G, Di Biagio, A, Parisini, A, Carbonara, S, Angarano, G, Purgatorio, M, Matteelli, A, Apostoli, A, Miro, J, Manzardo, C, Ligero, C, Gonzalez, J, Martinez-Martinez, J, Sanchez, F, Knobel, H, Salvado, M, Lopez-Colomes, J, Martinez-Lacasa, X, Cuchi, E, Falco, V, Curran, A, Tortola, M, Ocana, I, Vidal, R, Sambeat, M, Pomar, V, Coll, P, Pozamczer, D, Saumoy, M, Alcaide, F, Cayla, J, Moreno, A, Millet, J, Orcau, A, Fina, L, Romero, A, Roldan, L, Iribarren, J, Ibarguren, M, Moreno, S, Gonzalez, A, Miralles, P, Aldamiz-Echevarria, T, Losso, M, Toibaro, J, Gambardella, L, Moreno Macias, L, Warley, E, Tavella, S, Garcia Messina, O, Gear, O, Laplume, H, Marson, C, Contarelia, J, Michaan, M, Scapellato, P, Bartoletti, B, Palmero, D, Elias, C, Cortes, C, Crabtree, B, Mosqueda Gomez, J, Villanueva, J, Gonzalez Hernandez, L, Badial, F, Kraef C., Bentzon A., Panteleev A., Skrahina A., Bolokadze N., Tetradov S., Podlasin R., Karpov I., Borodulina E., Denisova E., Azina I., Lundgren J., Johansen I. S., Mocroft A., Podlekareva D., Kirk O., Vassilenko A., Klimuk D., Kondratenko O., Zalutskaya A., Bondarenko V., Mitsura V., Kozorez E., Tumash O., Suetnov O., Paduto D., Iljina V., Kummik T., Mshvidobadze K., Lanchava N., Goginashvili L., Mikiashvili L., Bablishvili N., Rozentale B., Zeltina I., Janushkevich I., Caplinskiene I., Caplinskas S., Kancauskiene Z., Wiercinska-Drapalo A., Thompson M., Kozlowska J., Grezesczuk A., Bura M., Knysz B., Inglot M., Garlicki A., Loster J., uiculescu D. D., Rakhmanova A., Panteleev O., Yakovlev A., Kozlov A., Tyukalova A., Vlasova Y., rofimov T. T., Kyselyova G., Obel N., Gerstoft J., Kronborg G., Payen M. C., abeya K. K., Necsoi C., Dabis F., Tsaranazy A., Cazanave C., Furrer H., Sagette M., Rickenbach M., Sculier D., Calmy A., Cavassini M., Bruno A., Bernasconi E., Hoffmann M., Vernazza P., Fehr J., Weber R., Miller R., Vora N., Cooke G., Mullaney S., Wilkins E., George V., Collini P., Dockrell D., Post F., Campbell L., Brum R., Mabonga E., Saigal P., Kegg S., Ainsworth J., Waters A., Dhar J., Ellis K., Girardi E., Rianda A., Galati V., Pinnetti C., Tommasi C., Lapadula G., Di Biagio A., Parisini A., Carbonara S., Angarano G., Purgatorio M., Matteelli A., Apostoli A., Miro J. M., Manzardo C., Ligero C., Gonzalez J., Martinez-Martinez J. A., Sanchez F., Knobel H., Salvado M., Lopez-Colomes J. L., Martinez-Lacasa X., Cuchi E., Falco V., Curran A., Tortola M. T., Ocana I., Vidal R., Sambeat M. A., Pomar V., Coll P., Pozamczer D., Saumoy M., Alcaide F., Cayla J., Moreno A., Millet J. P., Orcau A., Fina L., Romero A., Roldan L. L., Iribarren J. A., Ibarguren M., Moreno S., Gonzalez A., Miralles P., Aldamiz-Echevarria T., Losso M., Toibaro J., Gambardella L., Moreno Macias L., Warley E., Tavella S., Garcia Messina O., Gear O., Laplume H., Marson C., Contarelia J., Michaan M., Scapellato P., Bartoletti B., Palmero D., Elias C., Cortes C., Crabtree B., Mosqueda Gomez J. L., Villanueva J. A., Gonzalez Hernandez L. A., Badial F., Kraef, C, Bentzon, A, Panteleev, A, Skrahina, A, Bolokadze, N, Tetradov, S, Podlasin, R, Karpov, I, Borodulina, E, Denisova, E, Azina, I, Lundgren, J, Johansen, I, Mocroft, A, Podlekareva, D, Kirk, O, Vassilenko, A, Klimuk, D, Kondratenko, O, Zalutskaya, A, Bondarenko, V, Mitsura, V, Kozorez, E, Tumash, O, Suetnov, O, Paduto, D, Iljina, V, Kummik, T, Mshvidobadze, K, Lanchava, N, Goginashvili, L, Mikiashvili, L, Bablishvili, N, Rozentale, B, Zeltina, I, Janushkevich, I, Caplinskiene, I, Caplinskas, S, Kancauskiene, Z, Wiercinska-Drapalo, A, Thompson, M, Kozlowska, J, Grezesczuk, A, Bura, M, Knysz, B, Inglot, M, Garlicki, A, Loster, J, Uiculescu, D, Rakhmanova, A, Panteleev, O, Yakovlev, A, Kozlov, A, Tyukalova, A, Vlasova, Y, Rofimov, T, Kyselyova, G, Obel, N, Gerstoft, J, Kronborg, G, Payen, M, Abeya, K, Necsoi, C, Dabis, F, Tsaranazy, A, Cazanave, C, Furrer, H, Sagette, M, Rickenbach, M, Sculier, D, Calmy, A, Cavassini, M, Bruno, A, Bernasconi, E, Hoffmann, M, Vernazza, P, Fehr, J, Weber, R, Miller, R, Vora, N, Cooke, G, Mullaney, S, Wilkins, E, George, V, Collini, P, Dockrell, D, Post, F, Campbell, L, Brum, R, Mabonga, E, Saigal, P, Kegg, S, Ainsworth, J, Waters, A, Dhar, J, Ellis, K, Girardi, E, Rianda, A, Galati, V, Pinnetti, C, Tommasi, C, Lapadula, G, Di Biagio, A, Parisini, A, Carbonara, S, Angarano, G, Purgatorio, M, Matteelli, A, Apostoli, A, Miro, J, Manzardo, C, Ligero, C, Gonzalez, J, Martinez-Martinez, J, Sanchez, F, Knobel, H, Salvado, M, Lopez-Colomes, J, Martinez-Lacasa, X, Cuchi, E, Falco, V, Curran, A, Tortola, M, Ocana, I, Vidal, R, Sambeat, M, Pomar, V, Coll, P, Pozamczer, D, Saumoy, M, Alcaide, F, Cayla, J, Moreno, A, Millet, J, Orcau, A, Fina, L, Romero, A, Roldan, L, Iribarren, J, Ibarguren, M, Moreno, S, Gonzalez, A, Miralles, P, Aldamiz-Echevarria, T, Losso, M, Toibaro, J, Gambardella, L, Moreno Macias, L, Warley, E, Tavella, S, Garcia Messina, O, Gear, O, Laplume, H, Marson, C, Contarelia, J, Michaan, M, Scapellato, P, Bartoletti, B, Palmero, D, Elias, C, Cortes, C, Crabtree, B, Mosqueda Gomez, J, Villanueva, J, Gonzalez Hernandez, L, Badial, F, Kraef C., Bentzon A., Panteleev A., Skrahina A., Bolokadze N., Tetradov S., Podlasin R., Karpov I., Borodulina E., Denisova E., Azina I., Lundgren J., Johansen I. S., Mocroft A., Podlekareva D., Kirk O., Vassilenko A., Klimuk D., Kondratenko O., Zalutskaya A., Bondarenko V., Mitsura V., Kozorez E., Tumash O., Suetnov O., Paduto D., Iljina V., Kummik T., Mshvidobadze K., Lanchava N., Goginashvili L., Mikiashvili L., Bablishvili N., Rozentale B., Zeltina I., Janushkevich I., Caplinskiene I., Caplinskas S., Kancauskiene Z., Wiercinska-Drapalo A., Thompson M., Kozlowska J., Grezesczuk A., Bura M., Knysz B., Inglot M., Garlicki A., Loster J., uiculescu D. D., Rakhmanova A., Panteleev O., Yakovlev A., Kozlov A., Tyukalova A., Vlasova Y., rofimov T. T., Kyselyova G., Obel N., Gerstoft J., Kronborg G., Payen M. C., abeya K. K., Necsoi C., Dabis F., Tsaranazy A., Cazanave C., Furrer H., Sagette M., Rickenbach M., Sculier D., Calmy A., Cavassini M., Bruno A., Bernasconi E., Hoffmann M., Vernazza P., Fehr J., Weber R., Miller R., Vora N., Cooke G., Mullaney S., Wilkins E., George V., Collini P., Dockrell D., Post F., Campbell L., Brum R., Mabonga E., Saigal P., Kegg S., Ainsworth J., Waters A., Dhar J., Ellis K., Girardi E., Rianda A., Galati V., Pinnetti C., Tommasi C., Lapadula G., Di Biagio A., Parisini A., Carbonara S., Angarano G., Purgatorio M., Matteelli A., Apostoli A., Miro J. M., Manzardo C., Ligero C., Gonzalez J., Martinez-Martinez J. A., Sanchez F., Knobel H., Salvado M., Lopez-Colomes J. L., Martinez-Lacasa X., Cuchi E., Falco V., Curran A., Tortola M. T., Ocana I., Vidal R., Sambeat M. A., Pomar V., Coll P., Pozamczer D., Saumoy M., Alcaide F., Cayla J., Moreno A., Millet J. P., Orcau A., Fina L., Romero A., Roldan L. L., Iribarren J. A., Ibarguren M., Moreno S., Gonzalez A., Miralles P., Aldamiz-Echevarria T., Losso M., Toibaro J., Gambardella L., Moreno Macias L., Warley E., Tavella S., Garcia Messina O., Gear O., Laplume H., Marson C., Contarelia J., Michaan M., Scapellato P., Bartoletti B., Palmero D., Elias C., Cortes C., Crabtree B., Mosqueda Gomez J. L., Villanueva J. A., Gonzalez Hernandez L. A., and Badial F.

Abstract

Background: Early diagnosis of tuberculosis (TB) is important to reduce transmission, morbidity and mortality in people living with HIV (PLWH). Methods: PLWH with a diagnosis of TB were enrolled from HIV and TB clinics in Eastern Europe and followed until 24 months. Delayed diagnosis was defined as duration of TB symptoms (cough, weight-loss or fever) for ≥ 1 month before TB diagnosis. Risk factors for delayed TB diagnosis were assessed using multivariable logistic regression. The effect of delayed diagnosis on mortality was assessed using Kaplan–Meier estimates and Cox models. Findings: 480/740 patients (64.9%; 95% CI 61.3–68.3%) experienced a delayed diagnosis. Age ≥ 50 years (vs. < 50 years, aOR = 2.51; 1.18–5.32; p = 0.016), injecting drug use (IDU) (vs. non-IDU aOR = 1.66; 1.21–2.29; p = 0.002), being ART naïve (aOR = 1.77; 1.24–2.54; p = 0.002), disseminated TB (vs. pulmonary TB, aOR = 1.56, 1.10–2.19, p = 0.012), and presenting with weight loss (vs. no weight loss, aOR = 1.63; 1.18–2.24; p = 0.003) were associated with delayed diagnosis. PLWH with a delayed diagnosis were at 36% increased risk of death (hazard ratio = 1.36; 1.04–1.77; p = 0.023, adjusted hazard ratio 1.27; 0.95–1.70; p = 0.103). Conclusion: Nearly two thirds of PLWH with TB in Eastern Europe had a delayed TB diagnosis, in particular those of older age, people who inject drugs, ART naïve, with disseminated disease, and presenting with weight loss. Patients with delayed TB diagnosis were subsequently at higher risk of death in unadjusted analysis. There is a need for optimisation of the current TB diagnostic cascade and HIV care in PLWH in Eastern Europe.

Published
2021

6. Delayed diagnosis of tuberculosis in persons living with HIV in Eastern Europe: associated factors and effect on mortality-a multicentre prospective cohort study

Author

Kraef, Christian, Bentzon, Adrian, Panteleev, Alexander, Skrahina, Alena, Bolokadze, Natalie, Tetradov, Simona, Podlasin, Regina, Karpov, Igor, Borodulina, Elena, Denisova, Elena, Azina, Inga, Lundgren, Jens, Johansen, Isik Somuncu, Mocroft, Amanda, Podlekareva, Daria, Kirk, Ole, Vassilenko, A., Klimuk, D., Kondratenko, O., Zalutskaya, A., Bondarenko, V., Mitsura, V., Kozorez, E., Tumash, O., Suetnov, O., Paduto, D., Iljina, V., Kummik, T., Mshvidobadze, K., Lanchava, N., Goginashvili, L., Mikiashvili, L., Bablishvili, Nino, Rozentale, B., Zeltina, I., Janushkevich, I., Caplinskiene, I., Caplinskas, S., Kancauskiene, Z., Wiercinska-Drapalo, A., Thompson, M., Kozlowska, J., Grezesczuk, A., Bura, M., Knysz, B., Inglot, M., Garlicki, A., Loster, J., uiculescu, D.D., Rakhmanova, A., Panteleev, O., Yakovlev, A., Kozlov, A., Tyukalova, A., Vlasova, Y., rofimov, T.T., Kyselyova, G., Obel, N., Gerstoft, J., Kronborg, G., Payen, M.C., abeya, K.K., Necsoi, C., Dabis, F., Tsaranazy, A., Cazanave, C., Furrer, H., Sagette, M., Rickenbach, M., Sculier, D., Calmy, A., Cavassini, Matthias, Bruno, A., Bernasconi, E., Hoffmann, M., Vernazza, P., Fehr, J., Weber, R., Miller, R., Vora, N., Cooke, G., Mullaney, S., Wilkins, E., George, V., Collini, P., Dockrell, D., Post, F., Campbell, L., Brum, R., Mabonga, E., Saigal, P., Kegg, S., Ainsworth, J., Waters, A., Dhar, J., Ellis, K., Girardi, E., Rianda, A., Galati, V., Pinnetti, C., Tommasi, C., Lapadula, G., Di Biagio, A., Parisini, A., Carbonara, S., Angarano, G., Purgatorio, M., Matteelli, A., Apostoli, A., Miro, J.M., Manzardo, C., Ligero, C., Gonzalez, J., Martinez-Martinez, J.A., Sanchez, F., Knobel Freud, Hernando, Salvadó, M., Lopez-Colomes, J.L., Martínez-Lacasa, X., Cuchí, E., Falcó, Vicenç, Curran, Adrian, Tortola, M.T., Ocaña Rivera, Immaculada, Vidal, R., Sambeat, M.A., Pomar, Virginia, Coll, P., Pozamczer, D., Saumoy, M., Alcaide, Fernando, Caylà, Joan A, Moreno Camacho, Asunción, Millet, Joan-Pau, Orcau, Àngels, Fina, L., Romero, A., Roldan, L.L., Iribarren, J.A., Ibarguren, M., Moreno, S., González, A., Miralles, P., Aldámiz-Echevarría, T., Losso, M., Toibaro, J., Gambardella, L., Moreno Macias, L., Warley, E., Tavella, S., Garcia Messina, O., Gear, O., Laplume, H., Marson, C., Contarelia, J., Michaan, M., Scapellato, P., Bartoletti, B., Palmero, D., Elias, C., Cortes, C., Crabtree, B., Mosqueda Gomez, J.L., Villanueva, J.A., Gonzalez Hernandez, L.A., Badial, F., Kraef, C, Bentzon, A, Panteleev, A, Skrahina, A, Bolokadze, N, Tetradov, S, Podlasin, R, Karpov, I, Borodulina, E, Denisova, E, Azina, I, Lundgren, J, Johansen, I, Mocroft, A, Podlekareva, D, Kirk, O, Vassilenko, A, Klimuk, D, Kondratenko, O, Zalutskaya, A, Bondarenko, V, Mitsura, V, Kozorez, E, Tumash, O, Suetnov, O, Paduto, D, Iljina, V, Kummik, T, Mshvidobadze, K, Lanchava, N, Goginashvili, L, Mikiashvili, L, Bablishvili, N, Rozentale, B, Zeltina, I, Janushkevich, I, Caplinskiene, I, Caplinskas, S, Kancauskiene, Z, Wiercinska-Drapalo, A, Thompson, M, Kozlowska, J, Grezesczuk, A, Bura, M, Knysz, B, Inglot, M, Garlicki, A, Loster, J, Uiculescu, D, Rakhmanova, A, Panteleev, O, Yakovlev, A, Kozlov, A, Tyukalova, A, Vlasova, Y, Rofimov, T, Kyselyova, G, Obel, N, Gerstoft, J, Kronborg, G, Payen, M, Abeya, K, Necsoi, C, Dabis, F, Tsaranazy, A, Cazanave, C, Furrer, H, Sagette, M, Rickenbach, M, Sculier, D, Calmy, A, Cavassini, M, Bruno, A, Bernasconi, E, Hoffmann, M, Vernazza, P, Fehr, J, Weber, R, Miller, R, Vora, N, Cooke, G, Mullaney, S, Wilkins, E, George, V, Collini, P, Dockrell, D, Post, F, Campbell, L, Brum, R, Mabonga, E, Saigal, P, Kegg, S, Ainsworth, J, Waters, A, Dhar, J, Ellis, K, Girardi, E, Rianda, A, Galati, V, Pinnetti, C, Tommasi, C, Lapadula, G, Di Biagio, A, Parisini, A, Carbonara, S, Angarano, G, Purgatorio, M, Matteelli, A, Apostoli, A, Miro, J, Manzardo, C, Ligero, C, Gonzalez, J, Martinez-Martinez, J, Sanchez, F, Knobel, H, Salvado, M, Lopez-Colomes, J, Martinez-Lacasa, X, Cuchi, E, Falco, V, Curran, A, Tortola, M, Ocana, I, Vidal, R, Sambeat, M, Pomar, V, Coll, P, Pozamczer, D, Saumoy, M, Alcaide, F, Cayla, J, Moreno, A, Millet, J, Orcau, A, Fina, L, Romero, A, Roldan, L, Iribarren, J, Ibarguren, M, Moreno, S, Gonzalez, A, Miralles, P, Aldamiz-Echevarria, T, Losso, M, Toibaro, J, Gambardella, L, Moreno Macias, L, Warley, E, Tavella, S, Garcia Messina, O, Gear, O, Laplume, H, Marson, C, Contarelia, J, Michaan, M, Scapellato, P, Bartoletti, B, Palmero, D, Elias, C, Cortes, C, Crabtree, B, Mosqueda Gomez, J, Villanueva, J, Gonzalez Hernandez, L, and Badial, F

Subjects
medicine.medical_specialty, Tuberculosis, Delayed Diagnosis, Aged, Europe, Eastern, Humans, Middle Aged, Prospective Studies, HIV Infections, Tuberculosi, Epidemiology, Tuberculosis/diagnosis, HIV Infections/complications, Infectious and parasitic diseases, RC109-216, Eastern Europe, Eastern, Logistic regression, Europa de l'Est, Medical microbiology, Weight loss, Internal medicine, medicine, VIH (Virus), HIV Infection, Europe, Eastern/epidemiology, Prospective cohort study, Epidemiologia, business.industry, Proportional hazards model, Transmission (medicine), HIV (Viruses), Research, Hazard ratio, Delayed Diagnosi, medicine.disease, Europe, Prospective Studie, Infectious Diseases, medicine.symptom, business, Human
Abstract

Background Early diagnosis of tuberculosis (TB) is important to reduce transmission, morbidity and mortality in people living with HIV (PLWH). Methods PLWH with a diagnosis of TB were enrolled from HIV and TB clinics in Eastern Europe and followed until 24 months. Delayed diagnosis was defined as duration of TB symptoms (cough, weight-loss or fever) for ≥ 1 month before TB diagnosis. Risk factors for delayed TB diagnosis were assessed using multivariable logistic regression. The effect of delayed diagnosis on mortality was assessed using Kaplan–Meier estimates and Cox models. Findings 480/740 patients (64.9%; 95% CI 61.3–68.3%) experienced a delayed diagnosis. Age ≥ 50 years (vs. Conclusion Nearly two thirds of PLWH with TB in Eastern Europe had a delayed TB diagnosis, in particular those of older age, people who inject drugs, ART naïve, with disseminated disease, and presenting with weight loss. Patients with delayed TB diagnosis were subsequently at higher risk of death in unadjusted analysis. There is a need for optimisation of the current TB diagnostic cascade and HIV care in PLWH in Eastern Europe.

Published
2021
Full Text
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7. Healthcare delivery for HIV-positive people with tuberculosis in Europe

Author

Bentzon, A. K., Panteleev, A., Mitsura, V., Borodulina, E., Skrahina, A., Denisova, E., Tetradov, S., Podlasin, R., Riekstina, V., Kancauskiene, Z., Paduto, D., Mocroft, A., Trofimova, T., Miller, R., Post, F., Grezesczuk, A., Lundgren, J. D., Inglot, M., Podlekareva, D., Bolokadze, N., Kirk, O., Karpov, I., Vassilenko, A., Klimuk, D., Skrahin, A., Kondratenko, O., Zalutskaya, A., Bondarenko, V., Kozorez, E., Tumash, O., Suetnov, O., Iljina, V., Kummik, T., Mshvidobadze, K., Lanchava, N., Goginashvili, L., Mikiashvili, L., Bablishvili, N., Rozentale, B., Zeltina, I., Janushkevich, I., Caplinskiene, I., Caplinskas, S., Wiercinska-Drapalo, A., Thompson, M., Kozlowska, J., Bura, M., Knysz, B., Garlicki, A., Loster, J., Duiculescu, D., Rakhmanova, A., Panteleeva, O., Yakovlev, A., Kozlov, A., Tyukalova, A., Vlasova, Y., Trofimov, T., Kyselyova, G., Obel, N., Gerstoft, J., Kronborg, G., Payen, M. C., Kabeya, K., Necsoi, C., Dabis, F., Tsaranazy, A., Cazanave, C., Furrer, H., Sagette, M., Rickenbach, M., Elzi, L., Battegay, M., Sculier, D., Calmy, A., Cavassini, M., Bruno, A., Bernasconi, E., Hoffmann, M., Vernazza, P., Fehr, J., Weber, R., Vora, N., Cooke, G., Mullaney, S., Wilkins, E., George, V., Collini, P., Dockrell, D., Campbell, L., Brum, R., Mabonga, E., Saigal, P., Kegg, S., Ainsworth, J., Waters, A., Dhar, J., Ellis, K., Spallanzani, O. L., Girardi, E., Rianda, A., Galati, V., Pinnetti, C., Tommasi, C., San Gerardo, A. O., Lapadula, G., Di Biagio, A., Parisini, A., Carbonara, S., Angarano, G., Purgatorio, M., Matteelli, A., Apostoli, A., Miro, J. M., Manzardo, C., Ligero, C., Gonzalez, J., Martinez-Martinez, J. A., Sanchez, F., Knobel, H., Salvado, M., Lopez-Colomes, J. L., Martinez-Lacasa, X., Cuchi, E., Falco, V., Curran, A., Tortola, M. T., Ocana, I., Vidal, R., Sambeat, M. A., Pomar, V., Coll, P., Pozamczer, D., Saumoy, M., Alcaide, F., Cayla, J., Moreno, A., Millet, J. P., Orcau, A., Fina, L., Romero, A., Roldan, L. L., Iribarren, J. A., Ibarguren, M., Moreno, S., Gonzalez, A., Miralles, P., Aldamiz-Echevarria, T., Losso, M., Toibaro, J., Gambardella, L., Ramos Mejia, J. M., Moreno Macias, L., Warley, E., Tavella, S., Garcia Messina, O., Gear, O., Laplume, H., Marson, C., Contarelia, J., Michaan, M., Scapellato, P., Bartoletti, B., Palmero, D., Elias, C., Cortes, C., Crabtree, B., Mosqueda Gomez, J. L., Villanueva, J. A., Gonzalez Hernandez, L. A., and Badial, F.

Subjects
0301 basic medicine, medicine.medical_specialty, Rifabutin, Tuberculosis, Tuberculosi, Epidemiology, Antitubercular Agents, HIV Infections, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Moxifloxacin, Internal medicine, medicine, clinical management, VIH (Virus), Humans, Pharmacology (medical), 030212 general & internal medicine, Epidemiologia, coinfection, eastern Europe, HIV, tuberculosis, western Europe, Response rate (survey), GeneXpert MTB/RIF, business.industry, HIV (Viruses), Health Policy, medicine.disease, 030112 virology, Europe, Infectious Diseases, HIV-positive people, chemistry, Coinfection, Bedaquiline, business, Europa, Delivery of Health Care, medicine.drug
Abstract

Background: In a 2013 survey, we reported distinct discrepancies in delivery of tuberculosis (TB) and HIV services in eastern Europe (EE) vs. western Europe (WE). Objectives: To verify the differences in TB and HIV services in EE vs. WE. Methods: Twenty-three sites completed a survey in 2018 (EE, 14; WE, nine; 88% response rate). Results were compared across as well as within the two regions. When possible, results were compared with the 2013 survey. Results: Delivery of healthcare was significantly less integrated in EE: provision of TB and HIV services at one site (36% in EE vs. 89% in WE; P = 0.034), and continued TB follow-up in one location (42% vs. 100%; P = 0.007). Although access to TB diagnostics, standard TB and HIV drugs was generally good, fewer sites in EE reported unlimited access to rifabutin/multi-drug-resistant TB (MDR-TB) drugs, HIV integrase inhibitors and opioid substitution therapy (OST). Compared with 2013, routine usage of GeneXpert was more common in EE in 2018 (54% vs. 92%; P = 0.073), as was access to moxifloxacin (46% vs. 91%; P = 0.033), linezolid (31% vs. 64%; P = 0.217), and bedaquiline (0% vs. 25%; P = 0.217). Integration of TB and HIV services (46% vs. 39%; P = 1.000) and provision of OST to patients with opioid dependency (54% vs. 46%; P = 0.695) remained unchanged. Conclusion: Delivery of TB and HIV healthcare, including integration of TB and HIV care and access to MDR-TB drugs, still differs between WE and EE, as well as between individual EE sites.

Published
2020
Full Text
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8. Healthcare delivery for HIV-positive people with tuberculosis in Europe

Author

Bentzon, A. K., Panteleev, A., Mitsura, V., Borodulina, E., Skrahina, A., Denisova, E., Tetradov, S., Podlasin, R., Riekstina, V., Kancauskiene, Z., Paduto, D., Mocroft, A., Trofimova, T., Miller, R., Post, F., Grezesczuk, A., Lundgren, J. D., Inglot, M., Podlekareva, D., Bolokadze, N., Kirk, O., Karpov, I., Vassilenko, A., Klimuk, D., Skrahin, A., Kondratenko, O., Zalutskaya, A., Bondarenko, V., Kozorez, E., Tumash, O., Suetnov, O., Iljina, V., Kummik, T., Mshvidobadze, K., Lanchava, N., Goginashvili, L., Mikiashvili, L., Bablishvili, N., Rozentale, B., Zeltina, I., Janushkevich, I., Caplinskiene, I., Caplinskas, S., Wiercinska-Drapalo, A., Obel, N., Gerstoft, J., Kronborg, G., Hoffmann, M., Campbell, L., González, A., Bentzon, A. K., Panteleev, A., Mitsura, V., Borodulina, E., Skrahina, A., Denisova, E., Tetradov, S., Podlasin, R., Riekstina, V., Kancauskiene, Z., Paduto, D., Mocroft, A., Trofimova, T., Miller, R., Post, F., Grezesczuk, A., Lundgren, J. D., Inglot, M., Podlekareva, D., Bolokadze, N., Kirk, O., Karpov, I., Vassilenko, A., Klimuk, D., Skrahin, A., Kondratenko, O., Zalutskaya, A., Bondarenko, V., Kozorez, E., Tumash, O., Suetnov, O., Iljina, V., Kummik, T., Mshvidobadze, K., Lanchava, N., Goginashvili, L., Mikiashvili, L., Bablishvili, N., Rozentale, B., Zeltina, I., Janushkevich, I., Caplinskiene, I., Caplinskas, S., Wiercinska-Drapalo, A., Obel, N., Gerstoft, J., Kronborg, G., Hoffmann, M., Campbell, L., and González, A.

Abstract

Background: In a 2013 survey, we reported distinct discrepancies in delivery of tuberculosis (TB) and HIV services in eastern Europe (EE) vs. western Europe (WE). Objectives: To verify the differences in TB and HIV services in EE vs. WE. Methods: Twenty-three sites completed a survey in 2018 (EE, 14; WE, nine; 88% response rate). Results were compared across as well as within the two regions. When possible, results were compared with the 2013 survey. Results: Delivery of healthcare was significantly less integrated in EE: provision of TB and HIV services at one site (36% in EE vs. 89% in WE; P = 0.034), and continued TB follow-up in one location (42% vs. 100%; P = 0.007). Although access to TB diagnostics, standard TB and HIV drugs was generally good, fewer sites in EE reported unlimited access to rifabutin/multi-drug-resistant TB (MDR-TB) drugs, HIV integrase inhibitors and opioid substitution therapy (OST). Compared with 2013, routine usage of GeneXpert was more common in EE in 2018 (54% vs. 92%; P = 0.073), as was access to moxifloxacin (46% vs. 91%; P = 0.033), linezolid (31% vs. 64%; P = 0.217), and bedaquiline (0% vs. 25%; P = 0.217). Integration of TB and HIV services (46% vs. 39%; P = 1.000) and provision of OST to patients with opioid dependency (54% vs. 46%; P = 0.695) remained unchanged. Conclusion: Delivery of TB and HIV healthcare, including integration of TB and HIV care and access to MDR-TB drugs, still differs between WE and EE, as well as between individual EE sites.

Published
2021

9. Delayed diagnosis of tuberculosis in persons living with HIV in Eastern Europe:associated factors and effect on mortality—a multicentre prospective cohort study

Author

Kraef, Christian, Bentzon, Adrian, Panteleev, Alexander, Skrahina, Alena, Bolokadze, Natalie, Tetradov, Simona, Podlasin, Regina, Karpov, Igor, Borodulina, Elena, Denisova, Elena, Azina, Inga, Lundgren, Jens, Johansen, Isik Somuncu, Mocroft, Amanda, Podlekareva, Daria, Kirk, Ole, Vassilenko, A., Klimuk, D., Kondratenko, O., Zalutskaya, A., Bondarenko, V., Mitsura, V., Kozorez, E., Tumash, O., Suetnov, O., Paduto, D., Iljina, V., Kummik, T., Mshvidobadze, K., Lanchava, N., Goginashvili, L., Mikiashvili, L., Bablishvili, N., Rozentale, B., Zeltina, I., Janushkevich, I., Caplinskiene, I., Caplinskas, S., Kancauskiene, Z., Wiercinska-Drapalo, A., Thompson, M., Kozlowska, J., Grezesczuk, A., Bura, M., Knysz, B., Inglot, M., Garlicki, A., Obel, N., Gerstoft, J., Kronborg, G., Kraef, Christian, Bentzon, Adrian, Panteleev, Alexander, Skrahina, Alena, Bolokadze, Natalie, Tetradov, Simona, Podlasin, Regina, Karpov, Igor, Borodulina, Elena, Denisova, Elena, Azina, Inga, Lundgren, Jens, Johansen, Isik Somuncu, Mocroft, Amanda, Podlekareva, Daria, Kirk, Ole, Vassilenko, A., Klimuk, D., Kondratenko, O., Zalutskaya, A., Bondarenko, V., Mitsura, V., Kozorez, E., Tumash, O., Suetnov, O., Paduto, D., Iljina, V., Kummik, T., Mshvidobadze, K., Lanchava, N., Goginashvili, L., Mikiashvili, L., Bablishvili, N., Rozentale, B., Zeltina, I., Janushkevich, I., Caplinskiene, I., Caplinskas, S., Kancauskiene, Z., Wiercinska-Drapalo, A., Thompson, M., Kozlowska, J., Grezesczuk, A., Bura, M., Knysz, B., Inglot, M., Garlicki, A., Obel, N., Gerstoft, J., and Kronborg, G.

Abstract

Background: Early diagnosis of tuberculosis (TB) is important to reduce transmission, morbidity and mortality in people living with HIV (PLWH). Methods: PLWH with a diagnosis of TB were enrolled from HIV and TB clinics in Eastern Europe and followed until 24 months. Delayed diagnosis was defined as duration of TB symptoms (cough, weight-loss or fever) for ≥ 1 month before TB diagnosis. Risk factors for delayed TB diagnosis were assessed using multivariable logistic regression. The effect of delayed diagnosis on mortality was assessed using Kaplan–Meier estimates and Cox models. Findings: 480/740 patients (64.9%; 95% CI 61.3–68.3%) experienced a delayed diagnosis. Age ≥ 50 years (vs. < 50 years, aOR = 2.51; 1.18–5.32; p = 0.016), injecting drug use (IDU) (vs. non-IDU aOR = 1.66; 1.21–2.29; p = 0.002), being ART naïve (aOR = 1.77; 1.24–2.54; p = 0.002), disseminated TB (vs. pulmonary TB, aOR = 1.56, 1.10–2.19, p = 0.012), and presenting with weight loss (vs. no weight loss, aOR = 1.63; 1.18–2.24; p = 0.003) were associated with delayed diagnosis. PLWH with a delayed diagnosis were at 36% increased risk of death (hazard ratio = 1.36; 1.04–1.77; p = 0.023, adjusted hazard ratio 1.27; 0.95–1.70; p = 0.103). Conclusion: Nearly two thirds of PLWH with TB in Eastern Europe had a delayed TB diagnosis, in particular those of older age, people who inject drugs, ART naïve, with disseminated disease, and presenting with weight loss. Patients with delayed TB diagnosis were subsequently at higher risk of death in unadjusted analysis. There is a need for optimisation of the current TB diagnostic cascade and HIV care in PLWH in Eastern Europe.

Published
2021

10. TB research amidst the COVID-19 pandemic

Author

Graciaa, D. S., primary, Kempker, R. R., additional, Sanikidze, E., additional, Tukvadze, S., additional, Mikiashvili, L., additional, Aspindzelashvili, R., additional, Alkhazashvili, D., additional, Blumberg, H. M., additional, Avaliani, Z., additional, and Tukvadze, N., additional

Published
2021
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13. Major differences in organization and availability of health care and medicines for HIV/TB coinfected patients across Europe

Author

Mansfeld M., Skrahina A., Shepherd L., Schultze A., Panteleev A., Miller R., Miro J., Zeltina I., Tetradov S., Furrer H., Kirk O., Grzeszczuk A., Bolokadze N., Matteelli A., Post F., Lundgren J., Mocroft A., Efsen A., Podlekareva D., Losso M. H., Toibaro J. J., Palmero D., Bartoletti B. J., E. Warley, Gear O., Messina O. G., Michans M., Laplume H., David D., Marson C., Scapelatto F. P., Dalessandro D., Lupo S., Costilla Campero G., Herbst M., Remondegui C., Elias C., Karpov I., Vassilenko A., Skrahina E., Skrahin A., Zalutskya A., Kondratenko O., Mitsura V., Bondarenko V., Suetnov O., Paduto D., Dewit S., Payen M. C., Noscoi C., Kabeya K., M. Wolff, Cortes C., Obel N., Kronborg G., Iljna V., Kummik T., Bryand M., Dabis F., Lanchava N., Bablishvili N., Goginashvili L., Mikiashvili L., Mshvidobadze K., Girardi E., Di Biagio A., Apostoli A., Barzoni S., Lapadula G., Purgatorio M., Carbonara S., Rozentale B., Janushkevich I., Caplinskas S., Kancauskienne Z., Caplinskienne I., Crabtree B., Pina A., Madero J. S., Mosqueda J., Villanueva J. A., Bura M., Garlicki A., Inglot M., Knysz B., Kozlowska J., Loster J., Mularska E., Podlasin R., Thompson M., Wiercinska-Drapalo A., Duiculescu D., Rakhmanova A., Yakovlev A., Turkalova A., Vlasova Y., Trotimora T., Borodulina E., Chumanova L., Mashkova Y., Miro J. M., Cayla J. A., Moreno A., Millet J. P., Orcau A., Fina L., del Bano L., Roldan L. L., Romero A., Martinez J. A., Manzardo C., Gonzalez J., Tudo G., Knobel H., Sanchez F., Salvado M., Curran A., Tortola M. T., Pozamczer D., Saumoy M., Alcaide F., Martinez-Lacasa X., Cuchi E., Sambeat M. A., Pomar V., Coll P., Miralles P., Moreno S., Iribarren J. A., Ibarguren M., Aldamiz T., Rickenbach M., Sagette M., Post F. A., Miller R. F., Chapman A., Dockrell D., Wilkins E., Cooke G., Ainsworth J., Macallen D., Dhar J., Vora N., Mullaney S., Kegg S., Kyselyova G., Mansfeld, M, Skrahina, A, Shepherd, L, Schultze, A, Panteleev, A, Miller, R, Miro, J, Zeltina, I, Tetradov, S, Furrer, H, Kirk, O, Grzeszczuk, A, Bolokadze, N, Matteelli, A, Post, F, Lundgren, J, Mocroft, A, Efsen, A, Podlekareva, D, Losso, M, Toibaro, J, Palmero, D, Bartoletti, B, E., W, Gear, O, Messina, O, Michans, M, Laplume, H, David, D, Marson, C, Scapelatto, F, Dalessandro, D, Lupo, S, Costilla Campero, G, Herbst, M, Remondegui, C, Elias, C, Karpov, I, Vassilenko, A, Skrahina, E, Skrahin, A, Zalutskya, A, Kondratenko, O, Mitsura, V, Bondarenko, V, Suetnov, O, Paduto, D, Dewit, S, Payen, M, Noscoi, C, Kabeya, K, M., W, Cortes, C, Obel, N, Kronborg, G, Iljna, V, Kummik, T, Bryand, M, Dabis, F, Lanchava, N, Bablishvili, N, Goginashvili, L, Mikiashvili, L, Mshvidobadze, K, Girardi, E, Di Biagio, A, Apostoli, A, Barzoni, S, Lapadula, G, Purgatorio, M, Carbonara, S, Rozentale, B, Janushkevich, I, Caplinskas, S, Kancauskienne, Z, Caplinskienne, I, Crabtree, B, Pina, A, Madero, J, Mosqueda, J, Villanueva, J, Bura, M, Garlicki, A, Inglot, M, Knysz, B, Kozlowska, J, Loster, J, Mularska, E, Podlasin, R, Thompson, M, Wiercinska-Drapalo, A, Duiculescu, D, Rakhmanova, A, Yakovlev, A, Turkalova, A, Vlasova, Y, Trotimora, T, Borodulina, E, Chumanova, L, Mashkova, Y, Cayla, J, Moreno, A, Millet, J, Orcau, A, Fina, L, del Bano, L, Roldan, L, Romero, A, Martinez, J, Manzardo, C, Gonzalez, J, Tudo, G, Knobel, H, Sanchez, F, Salvado, M, Curran, A, Tortola, M, Pozamczer, D, Saumoy, M, Alcaide, F, Martinez-Lacasa, X, Cuchi, E, Sambeat, M, Pomar, V, Coll, P, Miralles, P, Moreno, S, Iribarren, J, Ibarguren, M, Aldamiz, T, Rickenbach, M, Sagette, M, Chapman, A, Dockrell, D, Wilkins, E, Cooke, G, Ainsworth, J, Macallen, D, Dhar, J, Vora, N, Mullaney, S, Kegg, S, and Kyselyova, G

Subjects
Tuberculosi, Coinfection, Health Policy, Antitubercular Agents, HIV, 1103 Clinical Sciences, HIV Infections, Eastern, Health Surveys, Article, Europe, Infectious Diseases, Cross-Sectional Studies, Rifabutin, Delivery of health care, Integrated, Tuberculosis, Europe, Eastern, Humans, Opiate Substitution Treatment, Pharmacology (medical), Virology, 610 Medicine & health
Abstract

Objectives: The aim of the study was to investigate the organization and delivery of HIV and tuberculosis (TB) health care and to analyse potential differences between treatment centres in Eastern (EE) and Western Europe (WE). Methods: Thirty-eight European HIV and TB treatment centres participating in the TB:HIV study within EuroCoord completed a survey on health care management for coinfected patients in 2013 (EE: 17 respondents; WE:21; 76% of all TB:HIV centres). Descriptive statistics were obtained for regional comparisons. The reported data on health care strategies were compared with actual clinical practice at patient level via data derived from the TB:HIV study. Results: Respondent centres in EE comprised: Belarus (n=3), Estonia (1), Georgia (1), Latvia (1), Lithuania (1), Poland (4), Romania (1), the Russian Federation (4) and Ukraine (1); those in WE comprised: Belgium (1), Denmark (1), France (1), Italy (7), Spain (2), Switzerland (1) and UK (8). Compared with WE, treatment of HIV and TB in EE are less often located at the same site (47% in EE versus 100% in WE; P

Published
2015

14. Clinical Outcomes Among Patients With Drug-resistant Tuberculosis Receiving Bedaquiline- or Delamanid-Containing Regimens.

Author

Kempker, R R, Mikiashvili, L, Zhao, Y, Benkeser, D, Barbakadze, K, Bablishvili, N, Avaliani, Z, Peloquin, C A, Blumberg, H M, and Kipiani, M

Subjects
*ANTITUBERCULAR agents, *DRUG side effects, *IMIDAZOLES, *LONGITUDINAL method, *MICROBIAL sensitivity tests, *SCIENTIFIC observation, *QUINOLINE, *SPUTUM, *TREATMENT effectiveness, *DESCRIPTIVE statistics
Abstract

Background Bedaquiline and delamanid are newly available drugs for treating multidrug-resistant tuberculosis (MDR-TB); however, there are limited data guiding their use and no comparison studies. Methods We conducted a prospective, observational study among patients with MDR-TB in Georgia who were receiving a bedaquiline- or delamanid-based treatment regimen. Monthly sputum cultures, minimal inhibitory concentration testing, and adverse event monitoring were performed. Primary outcomes were culture conversion rates and clinical outcomes. Targeted maximum likelihood estimation and super learning were utilized to produce a covariate-adjusted proportion of outcomes for each regimen. Results Among 156 patients with MDR-TB, 100 were enrolled and 95 were receiving a bedaquiline-based (n = 64) or delamanid-based (n = 31) regimen. Most were male (82%) and the median age was 38 years. Rates of previous treatment (56%) and cavitary disease (61%) were high. The most common companion drugs included linezolid, clofazimine, cycloserine, and a fluoroquinolone. The median numbers of effective drugs received among patients on bedaquiline-based (4; interquartile range [IQR], 4–4) and delamanid-based (4; IQR, 3.5–5) regimens were similar. Rates of acquired drug resistance were significantly higher among patients receiving delamanid versus bedaquiline (36% vs 10%, respectively; P <.01). Adjusted rates of sputum culture conversion at 2 months (67% vs 47%, respectively; P =.10) and 6 months (95% vs 74%, respectively; P <.01), as well as more favorable clinical outcomes (96% vs 72%, respectively; P <.01), were higher among patients receiving bedaquiline versus delamanid. Conclusions Among patients with MDR-TB, bedaquiline-based regimens were associated with higher rates of sputum culture conversion, more favorable outcomes, and a lower rate of acquired drug resistance versus delamanid-based regimens. [ABSTRACT FROM AUTHOR]

Published
2020
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15. Major differences in organization and availability of health care and medicines for HIV/TB coinfected patients across Europe

Author

Mansfeld, M, Skrahina, A, Shepherd, L, Schultze, A, Panteleev, A, Miller, R, Miro, J, Zeltina, I, Tetradov, S, Furrer, H, Kirk, O, Grzeszczuk, A, Bolokadze, N, Matteelli, A, Post, F, Lundgren, J, Mocroft, A, Efsen, A, Podlekareva, D, Losso, M, Toibaro, J, Palmero, D, Bartoletti, B, E., W, Gear, O, Messina, O, Michans, M, Laplume, H, David, D, Marson, C, Scapelatto, F, Dalessandro, D, Lupo, S, Costilla Campero, G, Herbst, M, Remondegui, C, Elias, C, Karpov, I, Vassilenko, A, Skrahina, E, Skrahin, A, Zalutskya, A, Kondratenko, O, Mitsura, V, Bondarenko, V, Suetnov, O, Paduto, D, Dewit, S, Payen, M, Noscoi, C, Kabeya, K, M., W, Cortes, C, Obel, N, Kronborg, G, Iljna, V, Kummik, T, Bryand, M, Dabis, F, Lanchava, N, Bablishvili, N, Goginashvili, L, Mikiashvili, L, Mshvidobadze, K, Girardi, E, Di Biagio, A, Apostoli, A, Barzoni, S, Lapadula, G, Purgatorio, M, Carbonara, S, Rozentale, B, Janushkevich, I, Caplinskas, S, Kancauskienne, Z, Caplinskienne, I, Crabtree, B, Pina, A, Madero, J, Mosqueda, J, Villanueva, J, Bura, M, Garlicki, A, Inglot, M, Knysz, B, Kozlowska, J, Loster, J, Mularska, E, Podlasin, R, Thompson, M, Wiercinska-Drapalo, A, Duiculescu, D, Rakhmanova, A, Yakovlev, A, Turkalova, A, Vlasova, Y, Trotimora, T, Borodulina, E, Chumanova, L, Mashkova, Y, Cayla, J, Moreno, A, Millet, J, Orcau, A, Fina, L, del Bano, L, Roldan, L, Romero, A, Martinez, J, Manzardo, C, Gonzalez, J, Tudo, G, Knobel, H, Sanchez, F, Salvado, M, Curran, A, Tortola, M, Pozamczer, D, Saumoy, M, Alcaide, F, Martinez-Lacasa, X, Cuchi, E, Sambeat, M, Pomar, V, Coll, P, Miralles, P, Moreno, S, Iribarren, J, Ibarguren, M, Aldamiz, T, Rickenbach, M, Sagette, M, Chapman, A, Dockrell, D, Wilkins, E, Cooke, G, Ainsworth, J, Macallen, D, Dhar, J, Vora, N, Mullaney, S, Kegg, S, Kyselyova, G, Mansfeld M., Skrahina A., Shepherd L., Schultze A., Panteleev A., Miller R., Miro J., Zeltina I., Tetradov S., Furrer H., Kirk O., Grzeszczuk A., Bolokadze N., Matteelli A., Post F., Lundgren J., Mocroft A., Efsen A., Podlekareva D., Losso M. H., Toibaro J. J., Palmero D., Bartoletti B. J., E. Warley, Gear O., Messina O. G., Michans M., Laplume H., David D., Marson C., Scapelatto F. P., Dalessandro D., Lupo S., Costilla Campero G., Herbst M., Remondegui C., Elias C., Karpov I., Vassilenko A., Skrahina E., Skrahin A., Zalutskya A., Kondratenko O., Mitsura V., Bondarenko V., Suetnov O., Paduto D., Dewit S., Payen M. C., Noscoi C., Kabeya K., M. Wolff, Cortes C., Obel N., Kronborg G., Iljna V., Kummik T., Bryand M., Dabis F., Lanchava N., Bablishvili N., Goginashvili L., Mikiashvili L., Mshvidobadze K., Girardi E., Di Biagio A., Apostoli A., Barzoni S., Lapadula G., Purgatorio M., Carbonara S., Rozentale B., Janushkevich I., Caplinskas S., Kancauskienne Z., Caplinskienne I., Crabtree B., Pina A., Madero J. S., Mosqueda J., Villanueva J. A., Bura M., Garlicki A., Inglot M., Knysz B., Kozlowska J., Loster J., Mularska E., Podlasin R., Thompson M., Wiercinska-Drapalo A., Duiculescu D., Rakhmanova A., Yakovlev A., Turkalova A., Vlasova Y., Trotimora T., Borodulina E., Chumanova L., Mashkova Y., Miro J. M., Cayla J. A., Moreno A., Millet J. P., Orcau A., Fina L., del Bano L., Roldan L. L., Romero A., Martinez J. A., Manzardo C., Gonzalez J., Tudo G., Knobel H., Sanchez F., Salvado M., Curran A., Tortola M. T., Pozamczer D., Saumoy M., Alcaide F., Martinez-Lacasa X., Cuchi E., Sambeat M. A., Pomar V., Coll P., Miralles P., Moreno S., Iribarren J. A., Ibarguren M., Aldamiz T., Rickenbach M., Sagette M., Post F. A., Miller R. F., Chapman A., Dockrell D., Wilkins E., Cooke G., Ainsworth J., Macallen D., Dhar J., Vora N., Mullaney S., Kegg S., Kyselyova G., Mansfeld, M, Skrahina, A, Shepherd, L, Schultze, A, Panteleev, A, Miller, R, Miro, J, Zeltina, I, Tetradov, S, Furrer, H, Kirk, O, Grzeszczuk, A, Bolokadze, N, Matteelli, A, Post, F, Lundgren, J, Mocroft, A, Efsen, A, Podlekareva, D, Losso, M, Toibaro, J, Palmero, D, Bartoletti, B, E., W, Gear, O, Messina, O, Michans, M, Laplume, H, David, D, Marson, C, Scapelatto, F, Dalessandro, D, Lupo, S, Costilla Campero, G, Herbst, M, Remondegui, C, Elias, C, Karpov, I, Vassilenko, A, Skrahina, E, Skrahin, A, Zalutskya, A, Kondratenko, O, Mitsura, V, Bondarenko, V, Suetnov, O, Paduto, D, Dewit, S, Payen, M, Noscoi, C, Kabeya, K, M., W, Cortes, C, Obel, N, Kronborg, G, Iljna, V, Kummik, T, Bryand, M, Dabis, F, Lanchava, N, Bablishvili, N, Goginashvili, L, Mikiashvili, L, Mshvidobadze, K, Girardi, E, Di Biagio, A, Apostoli, A, Barzoni, S, Lapadula, G, Purgatorio, M, Carbonara, S, Rozentale, B, Janushkevich, I, Caplinskas, S, Kancauskienne, Z, Caplinskienne, I, Crabtree, B, Pina, A, Madero, J, Mosqueda, J, Villanueva, J, Bura, M, Garlicki, A, Inglot, M, Knysz, B, Kozlowska, J, Loster, J, Mularska, E, Podlasin, R, Thompson, M, Wiercinska-Drapalo, A, Duiculescu, D, Rakhmanova, A, Yakovlev, A, Turkalova, A, Vlasova, Y, Trotimora, T, Borodulina, E, Chumanova, L, Mashkova, Y, Cayla, J, Moreno, A, Millet, J, Orcau, A, Fina, L, del Bano, L, Roldan, L, Romero, A, Martinez, J, Manzardo, C, Gonzalez, J, Tudo, G, Knobel, H, Sanchez, F, Salvado, M, Curran, A, Tortola, M, Pozamczer, D, Saumoy, M, Alcaide, F, Martinez-Lacasa, X, Cuchi, E, Sambeat, M, Pomar, V, Coll, P, Miralles, P, Moreno, S, Iribarren, J, Ibarguren, M, Aldamiz, T, Rickenbach, M, Sagette, M, Chapman, A, Dockrell, D, Wilkins, E, Cooke, G, Ainsworth, J, Macallen, D, Dhar, J, Vora, N, Mullaney, S, Kegg, S, Kyselyova, G, Mansfeld M., Skrahina A., Shepherd L., Schultze A., Panteleev A., Miller R., Miro J., Zeltina I., Tetradov S., Furrer H., Kirk O., Grzeszczuk A., Bolokadze N., Matteelli A., Post F., Lundgren J., Mocroft A., Efsen A., Podlekareva D., Losso M. H., Toibaro J. J., Palmero D., Bartoletti B. J., E. Warley, Gear O., Messina O. G., Michans M., Laplume H., David D., Marson C., Scapelatto F. P., Dalessandro D., Lupo S., Costilla Campero G., Herbst M., Remondegui C., Elias C., Karpov I., Vassilenko A., Skrahina E., Skrahin A., Zalutskya A., Kondratenko O., Mitsura V., Bondarenko V., Suetnov O., Paduto D., Dewit S., Payen M. C., Noscoi C., Kabeya K., M. Wolff, Cortes C., Obel N., Kronborg G., Iljna V., Kummik T., Bryand M., Dabis F., Lanchava N., Bablishvili N., Goginashvili L., Mikiashvili L., Mshvidobadze K., Girardi E., Di Biagio A., Apostoli A., Barzoni S., Lapadula G., Purgatorio M., Carbonara S., Rozentale B., Janushkevich I., Caplinskas S., Kancauskienne Z., Caplinskienne I., Crabtree B., Pina A., Madero J. S., Mosqueda J., Villanueva J. A., Bura M., Garlicki A., Inglot M., Knysz B., Kozlowska J., Loster J., Mularska E., Podlasin R., Thompson M., Wiercinska-Drapalo A., Duiculescu D., Rakhmanova A., Yakovlev A., Turkalova A., Vlasova Y., Trotimora T., Borodulina E., Chumanova L., Mashkova Y., Miro J. M., Cayla J. A., Moreno A., Millet J. P., Orcau A., Fina L., del Bano L., Roldan L. L., Romero A., Martinez J. A., Manzardo C., Gonzalez J., Tudo G., Knobel H., Sanchez F., Salvado M., Curran A., Tortola M. T., Pozamczer D., Saumoy M., Alcaide F., Martinez-Lacasa X., Cuchi E., Sambeat M. A., Pomar V., Coll P., Miralles P., Moreno S., Iribarren J. A., Ibarguren M., Aldamiz T., Rickenbach M., Sagette M., Post F. A., Miller R. F., Chapman A., Dockrell D., Wilkins E., Cooke G., Ainsworth J., Macallen D., Dhar J., Vora N., Mullaney S., Kegg S., and Kyselyova G.

Abstract

Objectives: The aim of the study was to investigate the organization and delivery of HIV and tuberculosis (TB) health care and to analyse potential differences between treatment centres in Eastern (EE) and Western Europe (WE). Methods: Thirty-eight European HIV and TB treatment centres participating in the TB:HIV study within EuroCoord completed a survey on health care management for coinfected patients in 2013 (EE: 17 respondents; WE:21; 76% of all TB:HIV centres). Descriptive statistics were obtained for regional comparisons. The reported data on health care strategies were compared with actual clinical practice at patient level via data derived from the TB:HIV study. Results: Respondent centres in EE comprised: Belarus (n=3), Estonia (1), Georgia (1), Latvia (1), Lithuania (1), Poland (4), Romania (1), the Russian Federation (4) and Ukraine (1); those in WE comprised: Belgium (1), Denmark (1), France (1), Italy (7), Spain (2), Switzerland (1) and UK (8). Compared with WE, treatment of HIV and TB in EE are less often located at the same site (47% in EE versus 100% in WE; P<0.001) and less often provided by the same doctors (41% versus 90%, respectively; P=0.002), whereas regular screening of HIV-infected patients for TB (80% versus 40%, respectively; P=0.037) and directly observed treatment (88% versus 20%, respectively; P<0.001) were more common in EE. The reported availability of rifabutin and second- and third-line anti-TB drugs was lower, and opioid substitution therapy (OST) was available at fewer centres in EE compared with WE (53% versus 100%, respectively; P<0.001). Conclusions: Major differences exist between EE and WE in relation to the organization and delivery of health care for HIV/TB-coinfected patients and the availability of anti-TB drugs and OST. Significant discrepancies between reported and actual clinical practices were found in EE.

Published
2015

16. Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB:HIV study

Author

Efsen, A, Schultze, A, Miller, R, Panteleev, A, Skrahin, A, Podlekareva, D, Miro, J, Girardi, E, Furrer, H, Losso, M, Toibaro, J, Cayla, J, Mocroft, A, Lundgren, J, Post, F, Kirk, O, Karpov, I, Vassilenko, A, Skrahina, A, Klimuk, D, Kondratenko, O, Zalutskaya, A, Bondarenko, V, Mitsura, V, Kozorez, E, Tumash, O, Suetnov, O, Paduto, D, Iljina, V, Kummik, T, Bolokadze, N, Mshvidobadze, K, Lanchava, N, Goginashvili, L, Mikiashvili, L, Bablishvili, N, Rozentale, B, Zeltina, I, Janushkevich, I, Caplinskiene, I, Caplinskas, S, Kancauskiene, Z, Podlasin, R, Wiercinska-Drapalo, A, Thompson, M, Kozlowska, J, Grezesczuk, A, Bura, M, Knysz, B, Inglot, M, Garlicki, A, Loster, J, Tetradov, S, Duiculescu, D, Rakhmanova, A, Panteleeva, O, Yakovlev, A, Kozlov, A, Tyukalova, A, Vlasova, Y, Trofimov, T, Kyselyova, G, Andersen, A, Thorsteinsson, K, Payen, M, Kabeya, K, Necsoi, C, Dabis, F, Bruyand, M, Morlat, P, Dupont, A, Gerard, Y, Bonnal, F, Ceccaldi, J, De Witte, S, Monlun, E, Lataste, P, Chossat, I, Vora, N, Cooke, G, Mullaney, S, Wilkins, E, George, V, Collini, P, Dockrell, D, Campbell, L, Brum, R, Mabonga, E, Saigal, P, Kegg, S, Ainsworth, J, Waters, A, Dhar, J, Mashonganyika, L, Rianda, A, Galati, V, Pinnetti, C, Tommasi, C, Lapadula, G, Di Biagio, A, Parisini, A, Carbonara, S, Angarano, G, Purgatorio, M, Matteelli, A, Apostoli, A, Macias, L, Warley, E, Tavella, S, Garcia Messina, O, Gear, O, Laplume, H, Marson, C, Contarelia, J, Michaan, M, Scapellato, P, Alessandro, D, Bartoletti, B, Palmero, D, Elias, C, Cortes, C, Crabtree, B, Mosqueda Gomez, J, Villanueva, A, Gonzalez Hernandez, L, Efsen, AMW, Miller, RF, Podlekareva, DN, Miro, JM, Losso, MH, Cayla, JA, Lundgren, JD, Post, FA, Andersen, AB, Payen, MC, Macias, LM, Alessandro, DD, Mosqueda Gomez, JL, Gonzalez Hernandez, LA, Efsen, A, Schultze, A, Miller, R, Panteleev, A, Skrahin, A, Podlekareva, D, Miro, J, Girardi, E, Furrer, H, Losso, M, Toibaro, J, Cayla, J, Mocroft, A, Lundgren, J, Post, F, Kirk, O, Karpov, I, Vassilenko, A, Skrahina, A, Klimuk, D, Kondratenko, O, Zalutskaya, A, Bondarenko, V, Mitsura, V, Kozorez, E, Tumash, O, Suetnov, O, Paduto, D, Iljina, V, Kummik, T, Bolokadze, N, Mshvidobadze, K, Lanchava, N, Goginashvili, L, Mikiashvili, L, Bablishvili, N, Rozentale, B, Zeltina, I, Janushkevich, I, Caplinskiene, I, Caplinskas, S, Kancauskiene, Z, Podlasin, R, Wiercinska-Drapalo, A, Thompson, M, Kozlowska, J, Grezesczuk, A, Bura, M, Knysz, B, Inglot, M, Garlicki, A, Loster, J, Tetradov, S, Duiculescu, D, Rakhmanova, A, Panteleeva, O, Yakovlev, A, Kozlov, A, Tyukalova, A, Vlasova, Y, Trofimov, T, Kyselyova, G, Andersen, A, Thorsteinsson, K, Payen, M, Kabeya, K, Necsoi, C, Dabis, F, Bruyand, M, Morlat, P, Dupont, A, Gerard, Y, Bonnal, F, Ceccaldi, J, De Witte, S, Monlun, E, Lataste, P, Chossat, I, Vora, N, Cooke, G, Mullaney, S, Wilkins, E, George, V, Collini, P, Dockrell, D, Campbell, L, Brum, R, Mabonga, E, Saigal, P, Kegg, S, Ainsworth, J, Waters, A, Dhar, J, Mashonganyika, L, Rianda, A, Galati, V, Pinnetti, C, Tommasi, C, Lapadula, G, Di Biagio, A, Parisini, A, Carbonara, S, Angarano, G, Purgatorio, M, Matteelli, A, Apostoli, A, Macias, L, Warley, E, Tavella, S, Garcia Messina, O, Gear, O, Laplume, H, Marson, C, Contarelia, J, Michaan, M, Scapellato, P, Alessandro, D, Bartoletti, B, Palmero, D, Elias, C, Cortes, C, Crabtree, B, Mosqueda Gomez, J, Villanueva, A, Gonzalez Hernandez, L, Efsen, AMW, Miller, RF, Podlekareva, DN, Miro, JM, Losso, MH, Cayla, JA, Lundgren, JD, Post, FA, Andersen, AB, Payen, MC, Macias, LM, Alessandro, DD, Mosqueda Gomez, JL, and Gonzalez Hernandez, LA

Abstract

Objectives Mortality among HIV patients with tuberculosis (TB) remains high in Eastern Europe (EE), but details of TB and HIV management remain scarce. Methods In this prospective study, we describe the TB treatment regimens of patients with multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). Results A total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug resistance) and 130 pan-susceptible TB. Adequate initial TB treatment was provided for 8% of patients with MDR-TB compared with 80% of those with pan-susceptible TB. By twelve months, an estimated 57.3% (95%CI 41.5–74.1) of MDR-TB patients had started adequate treatment. While 67% received ART, HIV-RNA suppression was demonstrated in only 23%. Conclusions Our results show that internationally recommended MDR-TB treatment regimens were infrequently used and that ART use and viral suppression was well below the target of 90%, reflecting the challenging patient population and the environment in which health care is provided. Urgent improvement of management of patients with TB/HIV in EE, in particular for those with MDR-TB, is needed and includes widespread access to rapid TB diagnostics, better access to and use of second-line TB drugs, timely ART initiation with viral load monitoring, and integration of TB/HIV care.

Published
2018

17. Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB:HIV study

Author

Efsen, A.M.W., primary, Schultze, A., additional, Miller, R.F., additional, Panteleev, A., additional, Skrahin, A., additional, Podlekareva, D.N., additional, Miro, J.M., additional, Girardi, E., additional, Furrer, H., additional, Losso, M.H., additional, Toibaro, J., additional, Caylà, J.A., additional, Mocroft, A., additional, Lundgren, J.D., additional, Post, F.A., additional, Kirk, O., additional, Karpov, I., additional, Vassilenko, A., additional, Skrahina, A., additional, Klimuk, D., additional, Kondratenko, O., additional, Zalutskaya, A., additional, Bondarenko, V., additional, Mitsura, V., additional, Kozorez, E., additional, Tumash, O., additional, Suetnov, O., additional, Paduto, D., additional, Iljina, V., additional, Kummik, T., additional, Bolokadze, N., additional, Mshvidobadze, K., additional, Lanchava, N., additional, Goginashvili, L., additional, Mikiashvili, L., additional, Bablishvili, N., additional, Rozentale, B., additional, Zeltina, I., additional, Janushkevich, I., additional, Caplinskiene, I., additional, Caplinskas, S., additional, Kancauskiene, Z., additional, Podlasin, R., additional, Wiercinska-Drapalo, A., additional, Thompson, M., additional, Kozlowska, J., additional, Grezesczuk, A., additional, Bura, M., additional, Knysz, B., additional, Inglot, M., additional, Garlicki, A., additional, Loster, J., additional, Tetradov, S., additional, Duiculescu, D., additional, Rakhmanova, A., additional, Panteleeva, O., additional, Yakovlev, A., additional, Kozlov, A., additional, Tyukalova, A., additional, Vlasova, Y., additional, Trofimov, T., additional, Kyselyova, G., additional, Andersen, A.B., additional, Thorsteinsson, K., additional, Payen, M.C., additional, Kabeya, K., additional, Necsoi, C., additional, Dabis, F., additional, Bruyand, M., additional, Morlat, P., additional, Dupont, A., additional, Gerard, Y., additional, Bonnal, F., additional, Ceccaldi, J., additional, De Witte, S., additional, Monlun, E., additional, Lataste, P., additional, Chossat, I., additional, Miller, R., additional, Vora, N., additional, Cooke, G., additional, Mullaney, S., additional, Wilkins, E., additional, George, V., additional, Collini, P., additional, Dockrell, D., additional, Post, F., additional, Campbell, L., additional, Brum, R., additional, Mabonga, E., additional, Saigal, P., additional, Kegg, S., additional, Ainsworth, J., additional, Waters, A., additional, Dhar, J., additional, Mashonganyika, L., additional, Rianda, A., additional, Galati, V., additional, Pinnetti, C., additional, Tommasi, C., additional, Lapadula, G., additional, Di Biagio, A., additional, Parisini, A., additional, Carbonara, S., additional, Angarano, G., additional, Purgatorio, M., additional, Matteelli, A., additional, Apostoli, A., additional, Macias, L. Moreno, additional, Warley, E., additional, Tavella, S., additional, Garcia Messina, O., additional, Gear, O., additional, Laplume, H., additional, Marson, C., additional, Contarelia, J., additional, Michaan, M., additional, Scapellato, P., additional, Alessandro, D.D., additional, Bartoletti, B., additional, Palmero, D., additional, Elias, C., additional, Cortes, C., additional, Crabtree, B., additional, Mosqueda Gomez, J.L., additional, Villanueva, A., additional, and Gonzalez Hernandez, L.A., additional

Published
2018
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18. Tuberculosis-related mortality in people living with HIV in Europe and Latin America: An international cohort study

Author

Podlekareva Daria, N, Efsen Anne Marie, W, Schultze, A, Post Frank, A, Skrahina Alena, M, Panteleev, A, Furrer, H, Miller Robert, F, Losso, M. H, Toibaro, J, Miro Jose, M, Vassilenko, A, Girardi, Enrico, Bruyand, M, Obel, N, Lundgren Jens, D, Mocroft, A, Kirk, O, Karpov, I, Skrahina, A, Klimuk, D, Skrahin, A, Kondratenko, O, Zalutskaya, A, Bondarenko, V, Mitsura, V, Kozorez, E, Tumash, O, Suetnov, O, Paduto, D, Iljina, V, Kummik, T, Bolokadze, N, Mshvidobadze, K, Lanchava, N, Goginashvili, L, Mikiashvili, L, Bablishvili, N, Rozentale, B, Zeltina, I, Janushkevich, I, Caplinskiene, I, Caplinskas, S, Kancauskiene, Z, Podlasin, R, Wiercinska Drapalo, A, Thompson, M, Kozlowska, J, Grezesczuk, A, Bura, M, Knysz, B, Inglot, M, Garlicki, A, Loster, J, Duiculescu, D, Tetradov, S, Rakhmanova, A, Panteleeva, O, Yakovlev, A, Kozlov, A, Tyukalova, A, Vlasova, Y, Trofimov, T, Kyselyova, G, Thorsteinsson, K, Payen, Mc, Kabeya, K, Necsoi, C, Dabis, F, Morlat, P, Dupont, A, Gerard, Y, Bonnal, F, Ceccaldi, J, De Witte, S, Monlun, E, Lataste, P, Chossat, I, Sagette, M, Rickenbach, M, Elzi, L, Battegay, M, Sculier, D, Calmy, A, Cavassini, M, Bruno, A, Bernasconi, E, Hoffmann, M, Vernazza, P, Fehr, J, Weber, R, Aubert, V, Böni, J, Bucher, Hc, Burton Jeangros, C, Dollenmaier, G, Egger, M, Fellay, J, Fux, Ca, Gorgievski, M, Günthard, H, Haerry, D, Hasse, B, Hirsch, Hh, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, R, Kovari, H, Ledergerber, B, Martinetti, G, Martinez de Tejada, B, Metzner, K, Müller, N, Nadal, D, Nicca, D, Pantaleo, G, Rauch, A, Regenass, S, Rudin, C, Schöni Affolter, F, Schmid, P, Schüpbach, J, Speck, R, Tarr, P, Telenti, A, Trkola, A, Yerly, S, Miller, Rf, Vora, N, Cooke, G, Mullaney, S, Wilkins, E, George, V, Collini, P, Dockrell, D, Post, F, Campbell, L, Brum, R, Mabonga, E, Saigal, P, Kegg, S, Ainsworth, J, Waters, A, Dhar, J, Mashonganyika, L, Girardi, E, Rianda, A, Galati, V, Pinnetti, C, Tommasi, C, Lapadula, G, Di Biagio, A, Parisini, A, Carbonara, S, Angarano, G, Purgatorio, M, Matteelli, Alberto, Apostoli, A, Miro, Jm, Manzardo, C, Ligero, C, Gonzalez, J, Martinez Martinez, Ja, Sanchez, F, Knobel, H, Salvadó, M, Lopez Colomes, Jl, Martínez Lacasa, X, Cuchí, E, Falcó, V, Curran, A, Tortola, Mt, Ocaña, I, Vidal, R, Sambeat, Ma, Pomar, V, Coll, P, Pozamczer, D, Saumoy, M, Alcaide, F, Caylà, J, Moreno, A, Millet, Jp, Orcau, A, Fina, L, Romero, A, Roldan, Ll, Iribarren, Ja, Ibarguren, M, Moreno, S, González, A, Miralles, P, Aldámiz Echevarría, T, Losso, M, Gambardella, L, Macias, L, Warley, E, Tavella, S, Messina, O, Gear, O, Laplume, H, Marson, C, Contarelia, J, Michaan, M, Scapellato, P, Alessandro, D, Bartoletti, B, Palmero, D, Elias, C, Cortes, C, Crabtree, B, Gomez, Jl, Hernandez, La, and Badial, F.

Subjects
Adult, Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Latin Americans, Tuberculosis, Anti-HIV Agents, Epidemiology, 030106 microbiology, Population, Infectious Diseases, Immunology, Virology, Antitubercular Agents, HIV Infections, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Tuberculosis, Multidrug-Resistant, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Young adult, Epidemics, education, Prospective cohort study, education.field_of_study, AIDS-Related Opportunistic Infections, business.industry, Mortality rate, Middle Aged, medicine.disease, Europe, Latin America, Female, business, Developed country, Demography, Cohort study
Abstract

Management of tuberculosis in patients with HIV in eastern Europe is complicated by the high prevalence of multidrug-resistant tuberculosis, low rates of drug susceptibility testing, and poor access to antiretroviral therapy (ART). We report 1 year mortality estimates from a multiregional (eastern Europe, western Europe, and Latin America) prospective cohort study: the TB:HIV study.Consecutive HIV-positive patients aged 16 years or older with a diagnosis of tuberculosis between Jan 1, 2011, and Dec 31, 2013, were enrolled from 62 HIV and tuberculosis clinics in 19 countries in eastern Europe, western Europe, and Latin America. The primary endpoint was death within 12 months after starting tuberculosis treatment; all deaths were classified according to whether or not they were tuberculosis related. Follow-up was either until death, the final visit, or 12 months after baseline, whichever occurred first. Risk factors for all-cause and tuberculosis-related deaths were assessed using Kaplan-Meier estimates and Cox models.Of 1406 patients (834 in eastern Europe, 317 in western Europe, and 255 in Latin America), 264 (19%) died within 12 months. 188 (71%) of these deaths were tuberculosis related. The probability of all-cause death was 29% (95% CI 26-32) in eastern Europe, 4% (3-7) in western Europe, and 11% (8-16) in Latin America (p0·0001) and the corresponding probabilities of tuberculosis-related death were 23% (20-26), 1% (0-3), and 4% (2-8), respectively (p0·0001). Patients receiving care outside eastern Europe had a 77% decreased risk of death: adjusted hazard ratio (aHR) 0·23 (95% CI 0·16-0·31). In eastern Europe, compared with patients who started a regimen with at least three active antituberculosis drugs, those who started fewer than three active antituberculosis drugs were at a higher risk of tuberculosis-related death (aHR 3·17; 95% CI 1·83-5·49) as were those who did not have baseline drug-susceptibility tests (2·24; 1·31-3·83). Other prognostic factors for increased tuberculosis-related mortality were disseminated tuberculosis and a low CD4 cell count. 18% of patients were receiving ART at tuberculosis diagnosis in eastern Europe compared with 44% in western Europe and 39% in Latin America (p0·0001); 12 months later the proportions were 67% in eastern Europe, 92% in western Europe, and 85% in Latin America (p0·0001).Patients with HIV and tuberculosis in eastern Europe have a risk of death nearly four-times higher than that in patients from western Europe and Latin America. This increased mortality rate is associated with modifiable risk factors such as lack of drug susceptibility testing and suboptimal initial antituberculosis treatment in settings with a high prevalence of drug resistance. Urgent action is needed to improve tuberculosis care for patients living with HIV in eastern Europe.EU Seventh Framework Programme.

Published
2016

19. Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis.

Author

Conradie, F., Bagdasaryan, T. R., Borisov, S., Howell, P., Mikiashvili, L., Ngubane, N., Samoilova, A., Skornykova, S., Tudor, E., Variava, E., Yablonskiy, P., Everitt, D., Wills, G. H., Sun, E., Olugbosi, M., Egizi, E., Li, M., Holsta, A., Timm, J., and Bateson, A.

Subjects
*TUBERCULOSIS, *LINEZOLID, *PERIPHERAL neuropathy, *DISEASE relapse, *POISONS, *ENTEROCOCCAL infections, *DRUG therapy for tuberculosis, *QUINOLINE, *RESEARCH, *RESEARCH methodology, *AMINOGLYCOSIDES, *EVALUATION research, *TREATMENT effectiveness, *IMIDAZOLES, *COMPARATIVE studies, *RANDOMIZED controlled trials, *ANTITUBERCULAR agents, *RESEARCH funding, *QUINOLONE antibacterial agents, *RIFAMPIN
Abstract

Background: The bedaquiline-pretomanid-linezolid regimen has been reported to have 90% efficacy against highly drug-resistant tuberculosis, but the incidence of adverse events with 1200 mg of linezolid daily has been high. The appropriate dose of linezolid and duration of treatment with this agent to minimize toxic effects while maintaining efficacy against highly drug-resistant tuberculosis are unclear.Methods: We enrolled participants with extensively drug-resistant (XDR) tuberculosis (i.e., resistant to rifampin, a fluoroquinolone, and an aminoglycoside), pre-XDR tuberculosis (i.e., resistant to rifampin and to either a fluoroquinolone or an aminoglycoside), or rifampin-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects. We randomly assigned the participants to receive bedaquiline for 26 weeks (200 mg daily for 8 weeks, then 100 mg daily for 18 weeks), pretomanid (200 mg daily for 26 weeks), and daily linezolid at a dose of 1200 mg for 26 weeks or 9 weeks or 600 mg for 26 weeks or 9 weeks. The primary end point in the modified intention-to-treat population was the incidence of an unfavorable outcome, defined as treatment failure or disease relapse (clinical or bacteriologic) at 26 weeks after completion of treatment. Safety was also evaluated.Results: A total of 181 participants were enrolled, 88% of whom had XDR or pre-XDR tuberculosis. Among participants who received bedaquiline-pretomanid-linezolid with linezolid at a dose of 1200 mg for 26 weeks or 9 weeks or 600 mg for 26 weeks or 9 weeks, 93%, 89%, 91%, and 84%, respectively, had a favorable outcome; peripheral neuropathy occurred in 38%, 24%, 24%, and 13%, respectively; myelosuppression occurred in 22%, 15%, 2%, and 7%, respectively; and the linezolid dose was modified (i.e., interrupted, reduced, or discontinued) in 51%, 30%, 13%, and 13%, respectively. Optic neuropathy developed in 4 participants (9%) who had received linezolid at a dose of 1200 mg for 26 weeks; all the cases resolved. Six of the seven unfavorable microbiologic outcomes through 78 weeks of follow-up occurred in participants assigned to the 9-week linezolid groups.Conclusions: A total of 84 to 93% of the participants across all four bedaquiline-pretomanid-linezolid treatment groups had a favorable outcome. The overall risk-benefit ratio favored the group that received the three-drug regimen with linezolid at a dose of 600 mg for 26 weeks, with a lower incidence of adverse events reported and fewer linezolid dose modifications. (Funded by the TB Alliance and others; ZeNix ClinicalTrials.gov number, NCT03086486.). [ABSTRACT FROM AUTHOR]

Published
2022
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20. The effect of anti-tuberculosis drug pharmacokinetics on QTc prolongation.

Author

Jin Y, Benkeser D, Kipiani M, Maranchick NF, Mikiashvili L, Barbakadze K, Avaliani Z, Alghamdi WA, Alshaer MH, Peloquin CA, Blumberg HM, and Kempker RR

Subjects
Humans, Male, Adult, Female, Antitubercular Agents adverse effects, Antitubercular Agents pharmacokinetics, Prospective Studies, Diarylquinolines adverse effects, Oxazoles adverse effects, Oxazoles pharmacokinetics, Nitroimidazoles adverse effects, Nitroimidazoles pharmacokinetics, Tuberculosis, Multidrug-Resistant drug therapy, Long QT Syndrome chemically induced
Abstract

Background: Implementation of newer anti-tuberculosis (TB) drugs may prolong the QT interval, increasing the risk of arrythmias and sudden cardiac death. The potential for cardiac adverse events has prompted recommendations for frequent cardiac monitoring during treatment. However, unknowns remain, including the association between drug concentrations and QT interval., Methods: An observational prospective cohort study design was used. Patients undergoing treatment for drug-resistant TB in Georgia were assessed. Serial blood samples were collected at 4-6 weeks for pharmacokinetics. Electrocardiograms were recommended to be performed monthly. A generalized estimating equation spline model was used to investigate (1) the effect difference between bedaquiline and delamanid, (2) the cumulative effect of number of anti-TB drugs, and (3) the relationship between serum drug concentrations on QTc interval., Results: Among 94 patients receiving either bedaquiline (n = 64) or delamanid (n = 30)-based treatment, most were male (82%), and the mean age was 39 years. The mean maximum QTc increase during the first six months was 37.5 ms (IQR: 17.8-56.8). Bedaquiline- and delamanid-based regimens displayed similar increased mean QTc change from baseline during drug administration (P = 0.12). Increasing number of anti-TB drugs was associated with an increased QTc (P = 0.01), but participants trended back towards baseline after drug discontinuation (P = 0.25). A significant association between AUC, C min , C max , and increased QTc interval was found for bedaquiline (months 1-6) and levofloxacin (months 1-12)., Conclusion: Bedaquiline- and delamanid-based regimens and increasing number of QT prolonging agents led to modest increases in the QTc interval with minimal clinical effect., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Published
2023
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21. Linezolid Exposure Is Associated with Cytopenias in Patients Treated for Multidrug-Resistant Tuberculosis.

Author

Graciaa DS, Kipiani M, Magee MJ, Mikiashvili L, Barbakadze K, Bablishvili N, Auld SC, Alghamdi WA, Alshaer MH, Peloquin CA, Avaliani Z, Blumberg HM, and Kempker RR

Subjects
Humans, Incidence, Linezolid adverse effects, Prospective Studies, Antitubercular Agents adverse effects, Tuberculosis, Multidrug-Resistant drug therapy
Abstract

Although linezolid is effective for multidrug-resistant TB (MDR-TB) tuberculosis treatment, it is associated with cytopenias after 4 weeks of administration. Data on toxicities with long-term use of linezolid and drug pharmacodynamics in MDR-TB treatment are limited, and concerns about toxicity present barriers to wider implementation. This was a secondary analysis of a prospective cohort study of patients treated for MDR-TB in the country of Georgia from 2015 to 2017. Intensive blood sampling 4 to 6 weeks after treatment initiation with linezolid 600 mg daily was performed for pharmacokinetic (PK) analysis, including linezolid trough concentration ( C min ) and area under the curve from 0 to 24 hours (AUC 0-24 was 0.235 mg/L (interquartile range [IQR], 0.069 to 0.529), and median AUC C was 89.6 mg·h/L (IQR, 69.2 to 116.2). Cytopenias were associated with linezolid PK parameters ( min  > 2 mg/L and AUC 0-24  > 160 mg·h/L). Cytopenias occurred frequently with long-term use of linezolid 600 mg/day and were associated with PK parameters but did not result in the need for treatment interruption in the management of a cohort of patients with MDR-TB.C min  > 2 mg/L and AUC 0-24  > 160 mg·h/L). Cytopenias occurred frequently with long-term use of linezolid 600 mg/day and were associated with PK parameters but did not result in the need for treatment interruption in the management of a cohort of patients with MDR-TB.

Published
2022
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22. Pharmacokinetics of bedaquiline, delamanid and clofazimine in patients with multidrug-resistant tuberculosis.

Author

Alghamdi WA, Al-Shaer MH, Kipiani M, Barbakadze K, Mikiashvili L, Kempker RR, and Peloquin CA

Subjects
Antitubercular Agents therapeutic use, Clofazimine, Diarylquinolines, Humans, Oxazoles, Prospective Studies, Nitroimidazoles, Tuberculosis, Multidrug-Resistant drug therapy
Abstract

Background: Pharmacokinetic data are needed for newly implemented anti-tuberculosis drugs to help optimize their use., Objectives: To help fill existing knowledge gaps, we evaluated the pharmacokinetic parameters of novel and repurposed anti-tuberculosis drugs among patients with drug-resistant pulmonary tuberculosis., Methods: A prospective cohort study among patients ≥16 years with confirmed pulmonary drug-resistant TB was conducted in Tbilisi, Georgia. Patients receiving bedaquiline, delamanid and/or clofazimine were included. Blood samples were collected 4-6 weeks after drug initiation, and serum concentrations were measured using validated liquid chromatography tandem mass spectrometry assays. A non-compartmental analysis was performed, and the association of exposure parameters with covariates was explored., Results: Among 99 patients, the average age and weight were 40 years and 65 kg, respectively. The median Cmin was 0.68 mg/L for bedaquiline, 0.17 mg/L for delamanid, and 0.52 mg/L for clofazimine. The median AUC0-24 was 30.6 mg·h/L for bedaquiline, 16.1 mg·h/L for clofazimine, and the AUC0-12 was 2.9 mg·h/L for delamanid. Among the significant covariates associated with drug exposure parameters were weight and sex for bedaquiline, alcohol use for delamanid, and weight for clofazimine., Conclusions: We found a strong association of weight with bedaquiline and clofazimine exposure parameters, suggesting the need for weight-based dosing for those agents., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2021
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23. Population Pharmacokinetics of Linezolid in Tuberculosis Patients: Dosing Regimen Simulation and Target Attainment Analysis.

Author

Alghamdi WA, Al-Shaer MH, An G, Alsultan A, Kipiani M, Barbakadze K, Mikiashvili L, Ashkin D, Griffith DE, Cegielski JP, Kempker RR, and Peloquin CA

Subjects
Anti-Bacterial Agents therapeutic use, Brazil, Georgia, Humans, Linezolid, Microbial Sensitivity Tests, Monte Carlo Method, Tuberculosis drug therapy, Tuberculosis, Multidrug-Resistant drug therapy
Abstract

The prolonged treatment duration for multidrug-resistant tuberculosis (MDR-TB) makes linezolid dosing difficult because of adverse effects associated with long-term use. We sought to find the optimal dosing regimen for linezolid across different MIC values. Pharmacokinetic (PK) data from TB patients were included from Brazil, Georgia, and two U.S. sites. Population PK modeling and simulation were performed. We used an f AUC (area under the unbound drug concentration-time curve)/MIC ratio of >119 as the PK/pharmacodynamic (PD) target and minimum (trough) concentrations of drug ( C min s) of 2 and 7 mg/liter as thresholds for toxicity. The PK/PD breakpoint was defined as the highest MIC at which the probability of target attainment is >90%. A total of 104 patients with pulmonary TB were included, with a median age and weight of 37 years and 60 kg. Eighty-one percent had drug-resistant TB. The PK data were best described by a one-compartment model. The PK/PD breakpoint was 0.125 mg/liter for a total daily dose of 300 mg, while daily doses of 450 to 600 mg and 900 to 1,200 mg had PK/PD breakpoints of 0.25 and 0.50 mg/liter, respectively. The probability of achieving a C min of ≤2 mg/liter was higher when the dose was given at once than when dividing it into 2 doses. Linezolid at a daily dose of 300 mg may not be optimal. We predicted an excellent and comparable efficacy of linezolid using total daily doses of 900 and 1,200 mg for MICs of ≤0.5 mg/liter but with the potential for more toxicity than with 600 mg daily. The increase in C min was noticeable when the daily dose was divided and may incur greater toxicity., (Copyright © 2020 American Society for Microbiology.)

Published
2020
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24. Fluoroquinolones in Drug-Resistant Tuberculosis: Culture Conversion and Pharmacokinetic/Pharmacodynamic Target Attainment To Guide Dose Selection.

Author

Al-Shaer MH, Alghamdi WA, Alsultan A, An G, Ahmed S, Alkabab Y, Banu S, Barbakadze K, Houpt E, Kipiani M, Mikiashvili L, Cegielski JP, Kempker RR, Heysell SK, and Peloquin CA

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Ciprofloxacin pharmacokinetics, Dose-Response Relationship, Drug, Female, Fluoroquinolones administration & dosage, Humans, Levofloxacin administration & dosage, Levofloxacin pharmacokinetics, Male, Microbial Sensitivity Tests, Middle Aged, Models, Biological, Moxifloxacin administration & dosage, Moxifloxacin pharmacokinetics, Ofloxacin pharmacokinetics, Retrospective Studies, Tuberculosis, Multidrug-Resistant microbiology, Tuberculosis, Pulmonary drug therapy, Tuberculosis, Pulmonary microbiology, Young Adult, Antitubercular Agents administration & dosage, Antitubercular Agents pharmacokinetics, Fluoroquinolones pharmacokinetics, Tuberculosis, Multidrug-Resistant drug therapy
Abstract

Fluoroquinolones are group A drugs in tuberculosis guidelines. We aim to compare the culture conversion between new-generation (levofloxacin and moxifloxacin) and old-generation (ciprofloxacin and ofloxacin) fluoroquinolones, develop pharmacokinetic models, and calculate target attainment for levofloxacin and moxifloxacin. We included three U.S. tuberculosis centers. Patients admitted between 1984 and 2015, infected with drug-resistant tuberculosis, and who had received fluoroquinolones for ≥28 days were included. Demographics, sputum cultures and susceptibility, treatment regimens, and serum concentrations were collected. A time-to-event analysis was conducted, and Cox proportional hazards model was used to compare the time to culture conversion. Using additional data from ongoing studies, pharmacokinetic modelling and Monte Carlo simulations were performed to assess target attainment for different doses. Overall, 124 patients received fluoroquinolones. The median age was 40 years, and the median weight was 60 kg. Fifty-six patients (45%) received old-generation fluoroquinolones. New-generation fluoroquinolones showed a faster time to culture conversion (median 16 versus 40 weeks, P  = 0.012). After adjusting for isoniazid and clofazimine treatment, patients treated with new-generation fluoroquinolones were more likely to have culture conversion (adjusted hazards ratio, 2.16 [95% confidence interval, 1.28 to 3.64]). We included 178 patients in the pharmacokinetic models. Levofloxacin and moxifloxacin were best described by a one-compartment model with first-order absorption and elimination. At least 1,500 to 1,750 mg levofloxacin and 800 mg moxifloxacin may be needed for maximum kill at the current epidemiologic cutoff values. In summary, new-generation fluoroquinolones showed faster time to culture conversion compared to the old generation. For optimal target attainment at the current MIC values, higher doses of levofloxacin and moxifloxacin may be needed., (Copyright © 2019 Al-Shaer et al.)

Published
2019
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25. Cycloserine Population Pharmacokinetics and Pharmacodynamics in Patients with Tuberculosis.

Author

Alghamdi WA, Alsultan A, Al-Shaer MH, An G, Ahmed S, Alkabab Y, Banu S, Barbakadze K, Houpt E, Kipiani M, Mikiashvili L, Schmidt S, Heysell SK, Kempker RR, Cegielski JP, and Peloquin CA

Subjects
Anti-Bacterial Agents therapeutic use, Cycloserine therapeutic use, Humans, Microbial Sensitivity Tests, Monte Carlo Method, Tuberculosis metabolism, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant metabolism, Anti-Bacterial Agents pharmacokinetics, Cycloserine pharmacokinetics, Tuberculosis drug therapy
Abstract

Limited pharmacokinetic/pharmacodynamic (PK/PD) data exist on cycloserine in tuberculosis (TB) patients. We pooled several studies into a large PK data set to estimate the population PK parameters for cycloserine in TB patients. We also performed simulations to provide insight into optimizing the dosing of cycloserine. TB patients were included from Georgia, Bangladesh, and four U.S. sites. Monolix and mlxR package were used for population PK modeling and simulation. We used PK/PD targets for time above MIC of ≥30% and ≥64%, representing bactericidal activity and 80% of the maximum kill, to calculate the probability of target attainment (PTA). Optimal PK/PD breakpoints were defined as the highest MIC to achieve ≥90% of PTA. Data from 247 subjects, including 205 patients with drug-resistant TB, were included. The data were best described by a one-compartment model. In most cases, the PK/PD breakpoints for the simulated regimens were similar for both PK/PD targets. Higher PTA were achieved as the total daily dose was increased. The highest PK/PD breakpoint that resulted from the use of 250 mg dosages was 16 mg/liter. For MICs of >16 mg/liter, doses of at least 500 mg three times daily or 750 mg twice daily were needed. In conclusion, the current dosing for cycloserine, 250 to 500 mg once or twice daily, is not sufficient for MICs of >16mg/liter. Further studies are needed regarding the efficacy and tolerability of daily doses of >1,000 mg. Dividing the dose minimally affected the PK/PD breakpoints while optimizing exposure, which can potentially reduce adverse drug effects., (Copyright © 2019 Alghamdi et al.)

Published
2019
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