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1. Population pharmacokinetics and pharmacogenetics of ritonavir-boosted darunavir in the presence of raltegravir or tenofovir disoproxil fumarate/emtricitabine in HIV-infected adults and the relationship with virological response:a sub-study of the NEAT001/ANRS143 randomized trial

Author

Dickinson L., Gurjar R., Stohr W., Bonora S., Owen A., D'Avolio A., Cursley A., Molina J. -M., Faetkenheuer G., Vandekerckhove L., Di Perri G., Pozniak A., Richert L., Raffi F., Boffito M., Dedes N., Chene G., Allavena C., Autran B., Antinori A., Bucciardini R., Vella S., Horban A., Arribas J., Babiker A. G., Pillay D., Franquet X., Schwarze S., Grarup J., Fischer A., Wallet C., Diallo A., Saillard J., Moecklinghoff C., Stellbrink H. -J., Vanleeuwen R., Gatell J., Sandstrom E., Flepp M., Ewings F., George E. C., Hudson F., Pearce G., Quercia R., Rogatto F., Leavitt R., Nguyen B. -Y., Peto T., Goebel F., Marcotullio S., Miller V., Sasieni P., Arnault F., Boucherie C., Jean D., Paniego V., Paraina F., Rouch E., Schwimmer C., Soussi M., Taieb A., Termote M., Touzeau G., Babiker A., Dodds W., Hoppe A., Kummeling I., Pacciarini F., Paton N., Russell C., Taylor K., Ward D., Aagaard B., Eid M., Gey D., Gramjensen B., Jakobsen M. -L., Jansson P. O., Jensen K., Mariajoensen Z., Moseholmlarsen E., Pahl C., Pearson M., Nielsen B. R., Reilev So. S., Christ I., Lathouwers D., Manting C., Van Leeuwen R., Mendy B., Metro A., Couffin-Cadiergues S., Knellwolf A. -L., Palmisiano L., Aznar E., Barea C., Cotarelo M., Esteban H., Girbau I., Moyano B., Ramirez M., Saiz C., Sanchez I., Yllescas M., Binelli A., Colasanti V., Massella M., Anagnostou O., Gioukari V., Touloumi G., Schmied B., Rieger A., Vetter N., Dewit S., Florence E., Gerstoft J., Mathiesen L., Katlama C., Cabie A., Cheret A., Dupon M., Ghosn J., Girard P. -M., Goujard C., Levy Y., Morlat P., Neau D., Obadia M., Perre P., Piroth L., Reynes J., Tattevin P., Ragnaud J. M., Weiss L., Yazdan Y., Yeni P., Zucman D., Esser S., Fatkenheuer G., Hoffmann C., Jessen H., Rockstroh J., Schmidt R., Stephan C., Unger S., Hatzakis A., Daikos G. L., Papadopoulos A., Skoutelis A., Banhegyi D., Mallon P., Mulcahy F., Andreoni M., Castelli F., D'Arminiomonforte A., Diperri G., Galli M., Lazzarin A., Mazzotta F., Torti C., Vullo V., Prins J., Richter C., Verhagen D., Vaneeden A., Doroana M., Antunes F., Maltez F., Sarmento-Castro R., Gonzalez Garcia J., Aldeguer J. L., Clotet B., Domingo P., Gatell J. M., Knobel H., Marquez M., Pilarmiralles M., Portilla J., Soriano V., Tellez M., Thalme A., Blaxhult A., Gisslen M., Winston A., Fox J., Gompels M., Herieka E., Johnson M., Leen C., Teague A., Williams I., Boyd M., Moller N. F., Moseholmlarsen E. F., Lemoing V., Wit F. W. N. M., Kowalska J., Berenguer J., Moreno S., Muller N. J., Torok E., Post F., Angus B., Calvez V., Boucher C., Collins S., Dunn D., Lambert S., Marcelin A. -G., Perno C. F., White E., Ammassari A., Schmidt R. E., Odermarsky M., Smith C., Thiebaut R., Delaserna J. I. B., Castagna A., De Wit S., Furrer H. -J., Mocroft A., Reiss P., Fragola V., Lauriola M., Murri R., Nieuwkerk P., Spire B., Volny-Anne A., West B., Amieva H., Llibre Codina J., Braggion M., Foca E., Dickinson, L., Gurjar, R., Stohr, W., Bonora, S., Owen, A., D'Avolio, A., Cursley, A., Molina, J. -M., Faetkenheuer, G., Vandekerckhove, L., Di Perri, G., Pozniak, A., Richert, L., Raffi, F., Boffito, M., Dedes, N., Chene, G., Allavena, C., Autran, B., Antinori, A., Bucciardini, R., Vella, S., Horban, A., Arribas, J., Babiker, A. G., Pillay, D., Franquet, X., Schwarze, S., Grarup, J., Fischer, A., Wallet, C., Diallo, A., Saillard, J., Moecklinghoff, C., Stellbrink, H. -J., Vanleeuwen, R., Gatell, J., Sandstrom, E., Flepp, M., Ewings, F., George, E. C., Hudson, F., Pearce, G., Quercia, R., Rogatto, F., Leavitt, R., Nguyen, B. -Y., Peto, T., Goebel, F., Marcotullio, S., Miller, V., Sasieni, P., Arnault, F., Boucherie, C., Jean, D., Paniego, V., Paraina, F., Rouch, E., Schwimmer, C., Soussi, M., Taieb, A., Termote, M., Touzeau, G., Babiker, A., Dodds, W., Hoppe, A., Kummeling, I., Pacciarini, F., Paton, N., Russell, C., Taylor, K., Ward, D., Aagaard, B., Eid, M., Gey, D., Gramjensen, B., Jakobsen, M. -L., Jansson, P. O., Jensen, K., Mariajoensen, Z., Moseholmlarsen, E., Pahl, C., Pearson, M., Nielsen, B. R., Reilev, So. S., Christ, I., Lathouwers, D., Manting, C., Van Leeuwen, R., Mendy, B., Metro, A., Couffin-Cadiergues, S., Knellwolf, A. -L., Palmisiano, L., Aznar, E., Barea, C., Cotarelo, M., Esteban, H., Girbau, I., Moyano, B., Ramirez, M., Saiz, C., Sanchez, I., Yllescas, M., Binelli, A., Colasanti, V., Massella, M., Anagnostou, O., Gioukari, V., Touloumi, G., Schmied, B., Rieger, A., Vetter, N., Dewit, S., Florence, E., Gerstoft, J., Mathiesen, L., Katlama, C., Cabie, A., Cheret, A., Dupon, M., Ghosn, J., Girard, P. -M., Goujard, C., Levy, Y., Morlat, P., Neau, D., Obadia, M., Perre, P., Piroth, L., Reynes, J., Tattevin, P., Ragnaud, J. M., Weiss, L., Yazdan, Y., Yeni, P., Zucman, D., Esser, S., Fatkenheuer, G., Hoffmann, C., Jessen, H., Rockstroh, J., Schmidt, R., Stephan, C., Unger, S., Hatzakis, A., Daikos, G. L., Papadopoulos, A., Skoutelis, A., Banhegyi, D., Mallon, P., Mulcahy, F., Andreoni, M., Castelli, F., D'Arminiomonforte, A., Diperri, G., Galli, M., Lazzarin, A., Mazzotta, F., Torti, C., Vullo, V., Prins, J., Richter, C., Verhagen, D., Vaneeden, A., Doroana, M., Antunes, F., Maltez, F., Sarmento-Castro, R., Gonzalez Garcia, J., Aldeguer, J. L., Clotet, B., Domingo, P., Gatell, J. M., Knobel, H., Marquez, M., Pilarmiralles, M., Portilla, J., Soriano, V., Tellez, M., Thalme, A., Blaxhult, A., Gisslen, M., Winston, A., Fox, J., Gompels, M., Herieka, E., Johnson, M., Leen, C., Teague, A., Williams, I., Boyd, M., Moller, N. F., Moseholmlarsen, E. F., Lemoing, V., Wit, F. W. N. M., Kowalska, J., Berenguer, J., Moreno, S., Muller, N. J., Torok, E., Post, F., Angus, B., Calvez, V., Boucher, C., Collins, S., Dunn, D., Lambert, S., Marcelin, A. -G., Perno, C. F., White, E., Ammassari, A., Schmidt, R. E., Odermarsky, M., Smith, C., Thiebaut, R., Delaserna, J. I. B., Castagna, A., De Wit, S., Furrer, H. -J., Mocroft, A., Reiss, P., Fragola, V., Lauriola, M., Murri, R., Nieuwkerk, P., Spire, B., Volny-Anne, A., West, B., Amieva, H., Llibre Codina, J., Braggion, M., Foca, E., Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, Global Health, APH - Personalized Medicine, APH - Mental Health, and Medical Psychology

Subjects
0301 basic medicine, Microbiology (medical), Adult, Male, medicine.medical_specialty, Anti-HIV Agents, 030106 microbiology, HIV Infections, Emtricitabine, 030226 pharmacology & pharmacy, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, immune system diseases, Internal medicine, Raltegravir Potassium, medicine, Humans, Pharmacology (medical), Tenofovir, Darunavir, Constitutive Androstane Receptor, Pharmacology, Ritonavir, biology, business.industry, Liver-Specific Organic Anion Transporter 1, virus diseases, Lopinavir, Viral Load, Raltegravir, Multidrug Resistance-Associated Protein 2, 3. Good health, NONMEM, SISTM, Infectious Diseases, Pharmacogenetics, biology.protein, Female, SLCO1B1, business, medicine.drug
Abstract

Objectives NEAT001/ANRS143 demonstrated non-inferiority of once-daily darunavir/ritonavir (800/100 mg) + twice-daily raltegravir (400 mg) versus darunavir/ritonavir + tenofovir disoproxil fumarate/emtricitabine (245/200 mg once daily) in treatment-naive patients. We investigated the population pharmacokinetics of darunavir, ritonavir, tenofovir and emtricitabine and relationships with demographics, genetic polymorphisms and virological failure. Methods Non-linear mixed-effects models (NONMEM v. 7.3) were applied to determine pharmacokinetic parameters and assess demographic covariates and relationships with SNPs (SLCO3A1, SLCO1B1, NR1I2, NR1I3, CYP3A5*3, CYP3A4*22, ABCC2, ABCC10, ABCG2 and SCL47A1). The relationship between model-predicted darunavir AUC0–24 and C24 with time to virological failure was evaluated by Cox regression. Results Of 805 enrolled, 716, 720, 347 and 361 were included in the darunavir, ritonavir, tenofovir and emtricitabine models, respectively (11% female, 83% Caucasian). No significant effect of patient demographics or SNPs was observed for darunavir or tenofovir apparent oral clearance (CL/F); coadministration of raltegravir did not influence darunavir or ritonavir CL/F. Ritonavir CL/F decreased by 23% in NR1I2 63396C>T carriers and emtricitabine CL/F was linearly associated with creatinine clearance (P Conclusions Darunavir concentrations were unaltered in the presence of raltegravir and not associated with virological failure. Polymorphisms investigated had little impact on study-drug pharmacokinetics. Darunavir/ritonavir + raltegravir may be an appropriate option for patients experiencing NRTI-associated toxicity.

Published
2020

2. Strategies to manage hepatitis C virus (HCV) disease burden

Author

Wedemeyer, H., Duberg, A. S., Buti, M., Rosenberg, W. M., Frankova, S., Esmat, G., Örmeci, N., Van Vlierberghe, H., Gschwantler, M., Akarca, U., Aleman, S., Balk, İ., Berg, T., Bihl, F., Bilodeau, M., Blasco, A. J., Brandão Mello, C. E., Bruggmann, P., Calinas, F., Calleja, J. L., Cheinquer, H., Christensen, P. B., Clausen, M., Coelho, H. S. M., Cornberg, M., Cramp, M. E., Dore, G. J., Doss, W., El-Sayed, M. H., Ergör, G., Estes, C., Falconer, K., Félix, J., Ferraz, M. L. G., Ferreira, P. R., García-Samaniego, J., Gerstoft, J., Giria, J. A., Gonçales, F. L., Jr, Guimarães Pessôa, M., Hézode, C., Hindman, S. J., Hofer, H., Husa, P., Idilman, R., Kåberg, M., Kaita, K. D. E., Kautz, A., Kaymakoglu, S., Krajden, M., Krarup, H., Laleman, W., Lavanchy, D., Lázaro, P., Marinho, R. T., Marotta, P., Mauss, S., Mendes Correa, M. C., Moreno, C., Müllhaupt, B., Myers, R. P., Nemecek, V., vrehus, A. L. H., Parkes, J., Peltekian, K. M., Ramji, A., Razavi, H., Reis, N., Roberts, S. K., Roudot-Thoraval, F., Ryder, S. D., Sarmento-Castro, R., Sarrazin, C., Semela, D., Sherman, M., Shiha, G. E., Sperl, J., Stärkel, P., Stauber, R. E., Thompson, A. J., Urbanek, P., Van Damme, P., van Thiel, I., Vandijck, D., Vogel, W., Waked, I., Weis, N., Wiegand, J., Yosry, A., Zekry, A., Negro, F., Sievert, W., and Gower, E.

Published
2014
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3. The present and future disease burden of hepatitis C virus (HCV) infection with todayʼs treatment paradigm

Author

Razavi, H., Waked, I., Sarrazin, C., Myers, R. P., Idilman, R., Calinas, F., Vogel, W., Mendes Correa, M. C., Hézode, C., Lázaro, P., Akarca, U., Aleman, S., Balk, İ., Berg, T., Bihl, F., Bilodeau, M., Blasco, A. J., Brandão Mello, C. E., Bruggmann, P., Buti, M., Calleja, J. L., Cheinquer, H., Christensen, P. B., Clausen, M., Coelho, H. S. M., Cramp, M. E., Dore, G. J., Doss, W., Duberg, A. S., El-Sayed, M. H., Ergör, G., Esmat, G., Falconer, K., Félix, J., Ferraz, M. L. G., Ferreira, P. R., Frankova, S., García-Samaniego, J., Gerstoft, J., Giria, J. A., Gonçales, F. L., Jr, Gower, E., Gschwantler, M., Guimarães Pessôa, M., Hindman, S. J., Hofer, H., Husa, P., Kåberg, M., Kaita, K. D. E., Kautz, A., Kaymakoglu, S., Krajden, M., Krarup, H., Laleman, W., Lavanchy, D., Marinho, R. T., Marotta, P., Mauss, S., Moreno, C., Murphy, K., Negro, F., Nemecek, V., Örmeci, N., vrehus, A. L. H., Parkes, J., Pasini, K., Peltekian, K. M., Ramji, A., Reis, N., Roberts, S. K., Rosenberg, W. M., Roudot-Thoraval, F., Ryder, S. D., Sarmento-Castro, R., Semela, D., Sherman, M., Shiha, G. E., Sievert, W., Sperl, J., Stärkel, P., Stauber, R. E., Thompson, A. J., Urbanek, P., Van Damme, P., van Thiel, I., Van Vlierberghe, H., Vandijck, D., Wedemeyer, H., Weis, N., Wiegand, J., Yosry, A., Zekry, A., Cornberg, M., Müllhaupt, B., and Estes, C.

Published
2014
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4. Historical epidemiology of hepatitis C virus (HCV) in selected countries

Author

Bruggmann, P., Berg, T., vrehus, A. L. H., Moreno, C., Brandão Mello, C. E., Roudot-Thoraval, F., Marinho, R. T., Sherman, M., Ryder, S. D., Sperl, J., Akarca, U., Balk, İ., Bihl, F., Bilodeau, M., Blasco, A. J., Buti, M., Calinas, F., Calleja, J. L., Cheinquer, H., Christensen, P. B., Clausen, M., Coelho, H. S. M., Cornberg, M., Cramp, M. E., Dore, G. J., Doss, W., Duberg, A. S., El-Sayed, M. H., Ergör, G., Esmat, G., Estes, C., Falconer, K., Félix, J., Ferraz, M. L. G., Ferreira, P. R., Frankova, S., García-Samaniego, J., Gerstoft, J., Giria, J. A., Gonçales, F. L., Jr, Gower, E., Gschwantler, M., Guimarães Pessôa, M., Hézode, C., Hofer, H., Husa, P., Idilman, R., Kåberg, M., Kaita, K. D. E., Kautz, A., Kaymakoglu, S., Krajden, M., Krarup, H., Laleman, W., Lavanchy, D., Lázaro, P., Marotta, P., Mauss, S., Mendes Correa, M. C., Müllhaupt, B., Myers, R. P., Negro, F., Nemecek, V., Örmeci, N., Parkes, J., Peltekian, K. M., Ramji, A., Razavi, H., Reis, N., Roberts, S. K., Rosenberg, W. M., Sarmento-Castro, R., Sarrazin, C., Semela, D., Shiha, G. E., Sievert, W., Stärkel, P., Stauber, R. E., Thompson, A. J., Urbanek, P., van Thiel, I., Van Vlierberghe, H., Vandijck, D., Vogel, W., Waked, I., Wedemeyer, H., Weis, N., Wiegand, J., Yosry, A., Zekry, A., Van Damme, P., Aleman, S., and Hindman, S. J.

Published
2014
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7. HIV Med

Author

ALEJOS, B., STELLA-ASCARIZ, N., MONTEJANO, R., RODRIGUEZ-CENTENO, J., SCHWIMMER, Christine, BERNARDINO, J. I., RODES, B., ESSER, S., GOUJARD, C., SARMENTO-CASTRO, R., DE MIGUEL, R., ESTEBAN-CANTOS, A., WALLET, C., RAFFI, F., and ARRIBAS, J. R.

Published
2019

8. Hepatitis C treatment outcome in former or current intravenous drug users coinfected with HIV, with or without directly observed therapy.

Author

Sarmento-Castro, R., Méndez, J., Horta, A., Gonçalves, C., Vasconcelos, O., Seabra, J., Abreu, M., Gonçalves, M. J., Santos, M. J., and Tavares, A. P.

Subjects
*DIRECTLY observed therapy, *HEPATITIS C, *TREATMENT effectiveness, *HIV, *HEPATITIS C virus
Abstract

Intravenous drug users (IDUs) with hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfection are recognised as a high-risk, vulnerable group. Between February 2015 and April 2018, a single-centre, non-interventional cohort study was conducted in an outpatient setting, to evaluate the sustained virologic response (SVR12) and assess treatment uptake models. The study included 385 former or recent IDUs divided into two groups: A-without use of opioid substitution treatment (OST) and B-patients taking opioid substitution; patients in group B received OST and self-administered therapy (B1) or OST and therapy under DOT (B2). Patients were characterised by demographic and clinical features and compared for treatment response. Correlations between SVR12 and independent variables were determined by logistic regression. Patients were mostly males (88.3%) with a mean age of 46 ± 5 years and HCV genotype 1a (63.7%). Approximately 28% were treatment-experienced and 84.9% received sofosbuvir/ledipasvir. The mean CD4+T count was 649 cells/mm3, and most individuals were on antiretroviral therapy with undetectable viral loads (97.4%). SVR12 was achieved in 94.8%, and only eight patients relapsed. No significant differences were found in treatment effect between individuals taking opioid substitutes under different treatment models. Correlations were found between HCV viral response and both HIV suppression and albumin levels. IDU with HCV/HIV coinfection, including individuals on self-administration of HCV therapy and opioid substitution treatments or in DOT programmes, are no longer considered a difficult-to-treat group, as they achieve high rates of SVR12. [ABSTRACT FROM AUTHOR]

Published
2021
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9. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: A modelling study

Author

Blach, S. Zeuzem, S. Manns, M. Altraif, I. Duberg, A.-S. Muljono, D.H. Waked, I. Alavian, S.M. Lee, M.-H. Negro, F. Abaalkhail, F. Abdou, A. Abdulla, M. Abou Rached, A. Aho, I. Akarca, U. Al Ghazzawi, I. Al Kaabi, S. Al Lawati, F. Al Namaani, K. Al Serkal, Y. Al-Busafi, S.A. Al-Dabal, L. Aleman, S. Alghamdi, A.S. Aljumah, A.A. Al-Romaihi, H.E. Andersson, M.I. Arendt, V. Arkkila, P. Assiri, A.M. Baatarkhuu, O. Bane, A. Ben-Ari, Z. Bergin, C. Bessone, F. Bihl, F. Bizri, A.R. Blachier, M. Blasco, A.J. Brandao Mello, C.E. Bruggmann, P. Brunton, C.R. Calinas, F. Chan, H.L.Y. Chaudhry, A. Cheinquer, H. Chen, C.-J. Chien, R.-N. Choi, M.S. Christensen, P.B. Chuang, W.-L. Chulanov, V. Cisneros, L. Clausen, M.R. Cramp, M.E. Craxi, A. Croes, E.A. Dalgard, O. Daruich, J.R. De Ledinghen, V. Dore, G.J. El-Sayed, M.H. Ergor, G. Esmat, G. Estes, C. Falconer, K. Farag, E. Ferraz, M.L.G. Ferreira, P.R. Flisiak, R. Frankova, S. Gamkrelidze, I. Gane, E. Garcia-Samaniego, J. Khan, A.G. Gountas, I. Goldis, A. Gottfredsson, M. Grebely, J. Gschwantler, M. Guimaraes Pessoa, M. Gunter, J. Hajarizadeh, B. Hajelssedig, O. Hamid, S. Hamoudi, W. Hatzakis, A. Himatt, S.M. Hofer, H. Hrstic, I. Hui, Y.-T. Hunyady, B. Idilman, R. Jafri, W. Jahis, R. Janjua, N.Z. Jarčuška, P. Jeruma, A. Jonasson, J.G. Kamel, Y. Kao, J.-H. Kaymakoglu, S. Kershenobich, D. Khamis, J. Kim, Y.S. Kondili, L. Koutoubi, Z. Krajden, M. Krarup, H. Lai, M.-S. Laleman, W. Lao, W.-C. Lavanchy, D. Lazaro, P. Leleu, H. Lesi, O. Lesmana, L.A. Li, M. Liakina, V. Lim, Y.-S. Luksic, B. Mahomed, A. Maimets, M. Makara, M. Malu, A.O. Marinho, R.T. Marotta, P. Mauss, S. Memon, M.S. Mendes Correa, M.C. Mendez-Sanchez, N. Merat, S. Metwally, A.M. Mohamed, R. Moreno, C. Mourad, F.H. Mullhaupt, B. Murphy, K. Nde, H. Njouom, R. Nonkovic, D. Norris, S. Obekpa, S. Oguche, S. Olafsson, S. Oltman, M. Omede, O. Omuemu, C. Opare-Sem, O. Ovrehus, A.L.H. Owusu-Ofori, S. Oyunsuren, T.S. Papatheodoridis, G. Pasini, K. Peltekian, K.M. Phillips, R.O. Pimenov, N. Poustchi, H. Prabdial-Sing, N. Qureshi, H. Ramji, A. Razavi-Shearer, D. Razavi-Shearer, K. Redae, B. Reesink, H.W. Ridruejo, E. Robbins, S. Roberts, L.R. Roberts, S.K. Rosenberg, W.M. Roudot-Thoraval, F. Ryder, S.D. Safadi, R. Sagalova, O. Salupere, R. Sanai, F.M. Sanchez Avila, J.F. Saraswat, V. Sarmento-Castro, R. Sarrazin, C. Schmelzer, J.D. Schreter, I. Seguin-Devaux, C. Shah, S.R. Sharara, A.I. Sharma, M. Shevaldin, A. Shiha, G.E. Sievert, W. Sonderup, M. Souliotis, K. Speiciene, D. Sperl, J. Starkel, P. Stauber, R.E. Stedman, C. Struck, D. Su, T.-H. Sypsa, V. Tan, S.-S. Tanaka, J. Thompson, A.J. Tolmane, I. Tomasiewicz, K. Valantinas, J. Van Damme, P. Van Der Meer, A.J. Van Thiel, I. Van Vlierberghe, H. Vince, A. Vogel, W. Wedemeyer, H. Weis, N. Wong, V.W.S. Yaghi, C. Yosry, A. Yuen, M.-F. Yunihastuti, E. Yusuf, A. Zuckerman, E. Razavi, H. The Polaris Observatory HCV Collaborators

Abstract

Background The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation. © 2017 Elsevier Ltd

Published
2017

10. Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study

Author

Razavi, H. Robbins, S. Zeuzem, S. Negro, F. Buti, M. Duberg, A. Roudot-Thoraval, F. Craxi, A. Manns, M. Marinho, R.T. Hunyady, B. Colombo, M. Aleman, S. Antonov, K. Arkkila, P. Athanasakis, K. Blach, S. Blachier, M. Blasco, A.J. Calinas, F. Calleja, J.L. Christensen, P.B. Cramp, M.E. Croes, E. de Knegt, R.J. de Ledinghen, V. Delile, J.-M. Estes, C. Falconer, K. Färkkilä, M. Flisiak, R. Frankova, S. Gamkrelidze, I. García-Samaniego, J. Genov, J. Gerstoft, J. Gheorghe, L. Goldis, A. Gountas, I. Gregorčič, S. Gschwantler, M. Gunter, J. Halota, W. Harcouet, L. Hézode, C. Hoffmann, P. Horvath, G. Hrstic, I. Jarčuška, P. Jelev, D. Jeruma, A. Kåberg, M. Kieran, J. Kondili, L.A. Kotzev, I. Krarup, H. Kristian, P. Lagging, M. Laleman, W. Lázaro, P. Liakina, V. Lukšić, B. Maimets, M. Makara, M. Mateva, L. Maticic, M. Mennini, F.S. Mitova, R. Moreno, C. Mossong, J. Murphy, K. Nde, H. Nemecek, V. Nonkovic, D. Norris, S. Oltman, M. Øvrehus, A.L.H. Papatheodoridis, G. Pasini, K. Razavi-Shearer, D. Razavi-Shearer, K. Reesink, H.W. Reic, T. Rozentale, B. Ryder, S.D. Salupere, R. Sarmento-Castro, R. Sarrazin, C. Schmelzer, J.D. Schréter, I. Seguin-Devaux, C. Simojoki, K. Simonova, M. Smit, P.J. Souliotis, K. Speiciene, D. Sperl, J. Stärkel, P. Struck, D. Sypsa, V. Thornton, L. Tolmane, I. Tomasiewicz, K. Valantinas, J. Van Damme, P. van de Vijver, D. van der Meer, A.J. van Santen, D. Van Vlierberghe, H. Vandijck, D. Vella, S. Videčnik-Zorman, J. Vogel, W. Weis, N. Hatzakis, A. The European Union HCV Collaborators

Abstract

Background Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide. In the European Union (EU), treatment and cure of HCV with direct-acting antiviral therapies began in 2014. WHO targets are to achieve a 65% reduction in liver-related deaths, a 90% reduction of new viral hepatitis infections, and 90% of patients with viral hepatitis infections being diagnosed by 2030. This study assessed the prevalence of HCV in the EU and the level of intervention required to achieve WHO targets for HCV elimination. Methods We populated country Markov models for the 28 EU countries through a literature search of PubMed and Embase between Jan 1, 2000, and March 31, 2016, and a Delphi process to gain expert consensus and validate inputs. We aggregated country models to create a regional EU model. We used the EU model to forecast HCV disease progression (considering the effect of immigration) and developed a strategy to acehive WHO targets. We used weighted average sustained viral response rates and fibrosis restrictions to model the effect of current therapeutic guidelines. We used the EU model to forecast HCV disease progression (considering the effect of immigration) under current screening and therapeutic guidelines. Additionally, we back-calculated the total number of patients needing to be screened and treated to achieve WHO targets. Findings We estimated the number of viraemic HCV infections in 2015 to be 3 238 000 (95% uncertainty interval [UI] 2 106 000–3 795 000) of a total population of 509 868 000 in the EU, equating to a prevalence of viraemic HCV of 0·64% (95% UI 0·41–0·74). We estimated that 1 180 000 (95% UI 1 003 000–1 357 000) people were diagnosed with viraemia (36·4%), 150 000 (12 000–180 000) were treated (4·6% of the total infected population or 12·7% of the diagnosed population), 133 000 (106 000–160 000) were cured (4·1%), and 57 900 (43 900–67 300) were newly infected (1·8%) in 2015. Additionally, 30 400 (26 600–42 500) HCV-positive immigrants entered the EU. To achieve WHO targets, unrestricted treatment needs to increase from 150 000 patients in 2015 to 187 000 patients in 2025 and diagnosis needs to increase from 88 800 new cases annually in 2015 to 180 000 in 2025. Interpretation Given its advanced health-care infrastructure, the EU is uniquely poised to eliminate HCV; however, expansion of screening programmes is essential to increase treatment to achieve the WHO targets. A united effort, grounded in sound epidemiological evidence, will also be necessary. Funding Gilead Sciences. © 2017 Elsevier Ltd

Published
2017

11. Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort

Author

GUARD C, Study Group, Hassanein, T, Bakalos, G, Ahlers, S, Shiffman, Ml, Tallarico, L, Reddy, Kr, Orlandini, A, Ferenci, P, Derbala, M, Coppola, C, Foster, Gr, Basho, J, Shabanaj, G, Harxhi, A, Debzi, N, Afredj, N, Guessab, N, Mahindad, N, Mahiou, H, Aissaoui, M, Al Qameesh, J, Al Ghandoor, Z, Assene, C, Bastens, B, Brixko, C, Cool, M, De Galocsy, C, Delwaide, J, George, C, Laukens, P, Lefebvre, V, Mulkay, Jp, Nevens, F, Servais, B, Van Vlierberghe, H, Horsmans, Y, Henrion, J, Sprengers, D, Michielsen, P, Bourgeois, S, Lasser, L, Langlet, P, Robaeys, G, Martinet, Jp, Warzee, P, Hoste, P, Reynaert, H, Juriens, I, Decaestecker, J, Van Der Meersch, F, Janssens, F, Ahmetagic, S, Verhaz, A, Bevanda, M, Calkic, L, Ibrahimpasic, N, Mesihovic, R, Mello, Ce, Ruiz, Fj, Martins Junior, E, Ferraz, Ml, Silva, G, Mendes, C, Lyra, A, Silva, Mh, Gomide, G, Fernandes, Jc, Pereira, P, Correa, Mc, Teixeira, R, Yousry, A, Hanno, A, Gabr, M, Omar, A, Esmat, G, Karatapanis, S, Nikolopoulou, V, Giannoulis, G, Manolakopoulos, S, Elefsiniotis, I, Drakoulis, C, Dimitroulopoulos, D, Kanatakis, S, Ketikoglou, I, Mimidis, K, Evgenidis, N, Akriviades, E, Vafiadi Zoubouli, I, Tsianos, E, Mela, M, Orfanou, E, Mousoulis, G, Karagiannis, I, Manesis, E, Varga, M, Nemesánszky, E, Fried, K, Schuller, J, Szalay, F, Lengyel, G, Tornai, I, Banyai, T, Lesch, M, Nagy, I, Gervain, J, Tusnadi, A, Schneider, F, Szentgyörgyi, L, Hunyady, B, Vincze, A, Tolvaj, G, Varkonyi, I, Makkai, E, Enyedi, J, Racz, I, Hausinger, P, Váczi, Z, Patai, Á, Ozsvár, Z, Lakner, L, Ribiczey, P, Bhalla, A, Somani, S, Luaia, R, Rao, P, Philip, M, Lawate, P, Nagral, A, Sood, A, Parikh, S, Merat, S, Nassiri Toosi, M, Alavian, Sm, Zali, Mr, Daryani, Ne, Drenaggi, D, Attili, Af, Bandiera, F, Bassi, P, Bellati, G, Bellantani, S, Brunetto, MAURIZIA ROSSANA, Bruno, S, Castelli, F, Castellacci, R, Cattelan, Am, Colombo, M, Craxi, A, D'Angelo, S, Colombo, S, Demelia, L, Di Perri, G, Di Giacomo, A, Ferrari, C, Francisci, D, Casinelli, K, Ganga, R, Costa, C, Mangia, A, Russo, Fp, Matarazzo, F, Mazzella, G, Mazzeo, M, Memoli, M, Montalbano, M, Montalto, G, Pieri, A, Passariello, N, Picciotto, A, Pietrangelo, A, Pirisi, M, Quirino, T, Raimondo, G, Rapaccini, Gl, Rizzardini, G, Rizzetto, M, Russello, M, Sabusco, G, Santantonio, T, Soardo, G, Amedea, A, Verucchi, G, Vinelli, F, Zignego, Al, Zuin, M, Ascione, A, Vinci, M, Pigozzi, Mg, Tundo, P, Saracco, Gm, Amoroso, P, Andreoni, M, Colletta, C, Erne, E, Megna, As, Biglino, A, Chiriaco, P, Foti, G, Spinzi, G, D'Amico, E, Paik, Sw, Ahn, Sh, Lee, Yn, Kim, Y, Yang, J, Han, Sy, Varghese, R, Al Gharabally, A, Askar, H, Sharara, A, Yaghi, C, Rached, Aa, Houmani, Z, Zaarour, F, Dohaibi, A, Ivanovski, L, Joksimovic, N, Abbas, Z, Memon, S, Mohsin, A, Masood, S, Hashmi, Z, Halota, W, Deron, Z, Mazur, W, Flisiak, R, Lipczynski, A, Musialik, J, Piekarska, A, Augustyniak, K, Baka Cwierz, B, Simon, K, Gietka, A, Berak, H, Sieklucki, J, Radowska, D, Szlauer, B, Piekos, T, Olszok, I, Jablkowski, M, Orszulak, G, Warakomska, I, Aleixo, Mj, Valente, C, Macedo, G, Sarmento Castro, R, Roxo, F, Faria, T, Mansinho, K, Velez, J, Ramos, Jp, Guerreiro, H, Alberto, S, Monteverde, C, Serejo, F, Peixe, P, Malhado, J, Curescu, M, Streinu Cercel, A, Caruntu, F, Livia, H, Preotescu, L, Arama, V, Ancuta, I, Gheorghe, L, Stanciu, C, Trifan, A, Acalovschi, M, Andreica, V, Pascu, O, Lencu, M, Sporea, I, Olteanu, D, Ionita Radu, F, Fierbinteanu Braticevici, C, Motoc, A, Silaghi, R, Musat, M, Coman, F, Stan, M, Cijevschi, C, Miftode, E, Delic, D, Jesic, R, Nozic, D, Svorcan, P, Fabri, M, Konstantinovic, L, Pelemis, M, Jankovic, G, Todorovic, Z, Nagorni, A, Kupcova, V, Skladany, L, Szantova, M, Krkoska, D, Jarcuska, P, Schreter, I, Oltman, M, Bocakova, J, Bunganic, I, Holoman, J, Giguere, A, Abdou, A. M., Basic (bio-) Medical Sciences, Gastroenterology, Laboratory of Molecullar and Cellular Therapy, Liver Cell Biology, Michielsen, Peter, GUARD-C Study Group, Graham R. Foster, Carmine Coppola, Moutaz Derbala, Peter Ferenci, Alessandra Orlandini, K. Rajender Reddy, Ludovico Tallarico, Mitchell L. Shiffman, Silke Ahler, Georgios Bakalo, Tarek Hassanein, GUARD-C Study Group: [.., Davide Drenaggi, Adolfo Francesco Attili, Franco Bandiera, Paolo Bassi, Giorgio Bellati, Stefano Bellantani, Maurizia Brunetto, Savino Bruno, Francesco Castelli, Roberto Castellacci, Anna Maria Cattelan, Massimo Colombo, Antonio Craxi, Salvatore D'angelo, Silvia Colombo, Luigi Demelia, Giovanni Di Perri, Antonio Di Giacomo, Carlo Ferrari, Daniela Francisci, Katia Casinelli, Roberto Ganga, Chiara Costa, Alessandra Mangia, Francesco Paolo Russo, Filippo Matarazzo, Giuseppe Mazzella, Maurizio Mazzeo, Massimo Memoli, Marzia Montalbano, Giuseppe Montalto, Alessandro Pieri, Nicola Passariello, Antonio Picciotto, Antonello Pietrangelo, Mario Pirisi, Tiziana Quirino, Giovanni Raimondo, Gian Ludovico Rapaccini, Giuliano Rizzardini, Mario Rizzetto, Maurizio Russello, Giuseppe Sabusco, Teresa Santantonio, Giorgio Soardo, Alessandri Amedea, Gabriella Verucchi, Francesco Vinelli, Anna Linda Zignego, Massimo Zuin, Antonio Ascione, Maria Vinci, Maria Graziella Pigozzi, Paolo Tundo, Giorgio Maria Saracco, Pietro Amoroso, Massimo Andreoni, Cosimo Colletta, Elke Erne, Angelo Salomone Megna, Alberto Biglino, Piergiorgio Chiriaco, Giuseppe Foti, Giancarlo Spinzi, Emilio D'amico, …], Foster G.R., Coppola C., Derbala M., Ferenci P., Orlandini A., Reddy K.R., Tallarico L., Shiffman M.L., Ahlers S., Bakalos G., Hassanein T., Basho J., Shabanaj G., Harxhi A., Debzi N., Afredj N., Guessab N., Mahindad N., Mahiou H., Aissaoui M., Al Qameesh J., Al Ghandoor Z., Assene C., Bastens B., Brixko C., Cool M., De Galocsy C., Delwaide J., George C., Laukens P., Lefebvre V., Mulkay J.-P., Nevens F., Servais B., Van Vlierberghe H., Horsmans Y., Henrion J., Sprengers D., Michielsen P., Bourgeois S., Lasser L., Langlet P., Robaeys G., Martinet J.-P., Warzee P., Hoste P., Reynaert H., Juriens I., Decaestecker J., Van Der Meersch F., Janssens F., Ahmetagic S., Verhaz A., Bevanda M., Calkic L., Ibrahimpasic N., Mesihovic R., Mello C.E., Ruiz F.J., Junior E.M., Ferraz M.L., Silva G., Mendes C., Lyra A., Silva M.H., Gomide G., Fernandes J.C., Pereira P., Correa M.C., Teixeira R., Yousry A., Hanno A., Gabr M., Omar A., Esmat G., Karatapanis S., Nikolopoulou V., Giannoulis G., Manolakopoulos S., Elefsiniotis I., Drakoulis C., Dimitroulopoulos D., Kanatakis S., Ketikoglou I., Mimidis K., Evgenidis N., Akriviades E., Vafiadi-Zoubouli I., Tsianos E., Mela M., Orfanou E., Mousoulis G., Karagiannis I., Manesis E., Varga M., Nemesanszky E., Fried K., Schuller J., Szalay F., Lengyel G., Tornai I., Banyai T., Lesch M., Nagy I., Gervain J., Tusnadi A., Schneider F., Szentgyorgyi L., Hunyady B., Vincze A., Tolvaj G., Varkonyi I., Makkai E., Enyedi J., Racz I., Hausinger P., Vaczi Z., Patai A., Ozsvar Z., Lakner L., Ribiczey P., Bhalla A., Somani S., Luaia R., Rao P., Philip M., Lawate P., Nagral A., Sood A., Parikh S., Merat S., Nassiri-Toosi M., Alavian S.-M., Zali M.R., Daryani N.E., Drenaggi D., Attili A.F., Bandiera F., Bassi P., Bellati G., Bellantani S., Brunetto M., Bruno S., Castelli F., Castellacci R., Cattelan A.M., Colombo M., Craxi A., D'angelo S., Colombo S., Demelia L., Di Perri G., Di Giacomo A., Ferrari C., Francisci D., Casinelli K., Ganga R., Costa C., Mangia A., Russo F.P., Matarazzo F., Mazzella G., Mazzeo M., Memoli M., Montalbano M., Montalto G., Pieri A., Passariello N., Picciotto A., Pietrangelo A., Pirisi M., Quirino T., Raimondo G., Rapaccini G.L., Rizzardini G., Rizzetto M., Russello M., Sabusco G., Santantonio T., Soardo G., Amedea A., Verucchi G., Vinelli F., Zignego A.L., Zuin M., Ascione A., Vinci M., Pigozzi M.G., Tundo P., Saracco G.M., Amoroso P., Andreoni M., Colletta C., Erne E., Megna A.S., Biglino A., Chiriaco P., Foti G., Spinzi G., D'amico E., Paik S.W., Ahn S.-H., Lee Y.N., Kim Y., Yang J., Han S.Y., Varghese R., Al Gharabally A., Askar H., Sharara A., Yaghi C., Abou Rached A., Houmani Z., Zaarour F., Dohaibi A., Ivanovski L., Joksimovic N., Abbas Z., Memon S., Mohsin A., Masood S., Hashmi Z., Halota W., Deron Z., Mazur W., Flisiak R., Lipczynski A., Musialik J., Piekarska A., Augustyniak K., Baka-Cwierz B., Simon K., Gietka A., Berak H., Sieklucki J., Radowska D., Szlauer B., Piekos T., Olszok I., Jablkowski M., Orszulak G., Warakomska I., Aleixo M.J., Valente C., Macedo G., Sarmento-Castro R., Roxo F., Faria T., Mansinho K., Velez J., Ramos J.P., Guerreiro H., Alberto S., Monteverde C., Serejo F., Peixe P., Malhado J., Curescu M., Streinu-Cercel A., Caruntu F., Livia H., Preotescu L., Arama V., Ancuta I., Gheorghe L., Stanciu C., Trifan A., Acalovschi M., Andreica V., Pascu O., Lencu M., Sporea I., Olteanu D., Ionita-Radu F., Fierbinteanu-Braticevici C., Motoc A., Silaghi R., Musat M., Coman F., Stan M., Cijevschi C., Miftode E., Delic D., Jesic R., Nozic D., Svorcan P., Fabri M., Konstantinovic L., Pelemis M., Jankovic G., Todorovic Z., Nagorni A., Kupcova V., Skladany L., Szantova M., Krkoska D., Jarcuska P., Schreter I., Oltman M., Bocakova J., Bunganic I., Holoman J., Giguere A., Abdou A.M.S., UCL - SSS/IREC-Institut de recherche expérimentale et clinique, UCL - SSS/IREC/GAEN-Pôle d'Hépato-gastro-entérologie, and UCL - (SLuc) Service de gastro-entérologie

Subjects
Genetics and Molecular Biology (all), Male, Chronic Hepatitis, Hepacivirus, Ribavirin/adverse effects, Asthenia/chemically induced, Polyethylene Glycol, Biochemistry, Polyethylene Glycols, Body Mass Index, Chronic Liver Disease, 0302 clinical medicine, Neutropenia/chemically induced, Interferon-alpha/adverse effects, Medicine, Chronic, lcsh:Science, Liver Diseases, virus diseases, Antiviral Agents/adverse effects, Cohort, Science & Technology - Other Topics, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Cohort study, Human, medicine.medical_specialty, Alpha interferon, Gastroenterology and Hepatology, Antiviral Agents, Microbiology, Dose-Response Relationship, 03 medical and health sciences, Pharmacotherapy, Hepatitis C, Chronic/drug therapy, Dose Prediction Methods, Drug Therapy, Anemia/chemically induced, Humans, Hemoglobin, Aged, Medicine and health sciences, Biochemistry, Genetics and Molecular Biology (all), Hepaciviru, Science & Technology, Dose-Response Relationship, Drug, Flaviviruses, lcsh:R, Organisms, Biology and Life Sciences, Proteins, medicine.disease, digestive system diseases, chemistry, Agricultural and Biological Sciences (all), Withholding Treatment, Asthenia, Immunology, Proportional Hazards Model, lcsh:Q, Human medicine, RNA viruses, Physiology, lcsh:Medicine, Peginterferon-alfa, Polyethylene Glycols/adverse effects, Adult, Anemia, Cohort Studies, Female, Hepatitis C, Chronic, Host-Pathogen Interactions, Interferon-alpha, Middle Aged, Neutropenia, Outcome Assessment (Health Care), Proportional Hazards Models, RNA, Viral, Recombinant Proteins, Ribavirin, Medicine (all), chemistry.chemical_compound, Outcome Assessment, Health Care, Medicine and Health Sciences, 030212 general & internal medicine, Viral, Pathology and laboratory medicine, Multidisciplinary, biology, Hepatitis C virus, Pharmaceutics, Hepatitis C, Hematology, Recombinant Protein, Outcome Assessment (Health Care)/methods, Medical microbiology, Host-Pathogen Interaction, Multidisciplinary Sciences, Physiological Parameters, Research Design, Combination, Viruses, Drug, Pathogens, Host-Pathogen Interactions/drug effects, Research Article, Clinical Research Design, Research and Analysis Methods, Internal medicine, Recombinant Proteins/adverse effects, RNA, Viral/blood, Antiviral Agent, business.industry, Body Weight, Hepacivirus/drug effects, Viral pathogens, biology.organism_classification, Hepatitis viruses, Microbial pathogens, RNA, Adverse Events, Cohort Studie, business
Abstract

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA

Published
2015

12. Determinants of blood telomere length in antiretroviral treatment‐naïve HIV‐positive participants enrolled in the NEAT 001/ANRS 143 clinical trial.

Author

Alejos, B, Stella‐Ascariz, N, Montejano, R, Rodriguez‐Centeno, J, Schwimmer, C, Bernardino, JI, Rodes, B, Esser, S, Goujard, C, Sarmento‐Castro, R, De Miguel, R, Esteban‐Cantos, A, Wallet, C, Raffi, F, and Arribas, JR

Subjects
HIV infection transmission, ANTIRETROVIRAL agents, AGE distribution, CLINICAL trials, CONFIDENCE intervals, HIV infections, HIV-positive persons, MULTIVARIATE analysis, POLYMERASE chain reaction, REGRESSION analysis, RNA, STATISTICS, TELOMERES, WHITE people, VIRAL load, QUANTITATIVE research, CROSS-sectional method, DESCRIPTIVE statistics, CD4 lymphocyte count
Abstract

Objectives: Our aim was to investigate factors associated with baseline blood telomere length in participants enrolled in NEAT 001/ANRS 143, a randomized, open‐label trial comparing ritonavir‐boosted darunavir (DRV/r) plus raltegravir (RAL) with DRV/r plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in antiretroviral therapy (ART)‐naïve HIV‐positive adults. Methods: A cross‐sectional study of 201 randomly selected participants who had stored samples available was carried out. We measured telomere length (i.e. the relative telomere length, calculated as the telomere to single copy gene ratio) at baseline with monochrome quantitative multiplex polymerase chain reaction (PCR). We used multivariable predictive linear regression to calculate mean differences and 95% confidence intervals (CIs) for the association between baseline telomere length and baseline characteristics. Results: The baseline characteristics of the 201 participants did not differ from those of the 805 participants in the parent trial population: 89% were male, the mean age was 39 years, 83.6% were Caucasian, 93% acquired HIV infection via sexual transmission, the mean estimated time since HIV diagnosis was 2.1 years, the mean HIV‐1 RNA load was 4.7 log10 HIV‐1 RNA copies/mL, the mean nadir and baseline CD4 counts were 301 and 324 cells/μL, respectively, and the mean CD4:CD8 ratio was 0.4. In the univariate analysis, shorter telomere length was associated with older age (per 10 years) (P < 0.001), HIV‐1 RNA ≥ 100 000 copies/mL (P = 0.001), CD4 count < 200 cells/μL (P = 0.037), lower CD4:CD8 ratio (P = 0.018), statin treatment (P = 0.004), and current alcohol consumption (P = 0.035). In the multivariable analysis, older age (P < 0.001) and HIV RNA ≥ 100 000 copies/mL (P = 0.054) were independently associated with shorter telomere length. Conclusions: Both age and HIV RNA viral load correlated with shorter blood telomere length in untreated persons living with HIV. These results suggest that HIV infection and age have synergistic and independent impacts upon immunosenescence. [ABSTRACT FROM AUTHOR]

Published
2019
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13. Host and disease factors are associated with cognitive function in European HIV-infected adults prior to initiation of antiretroviral therapy

Author

Winston, A, Stohr, W, Antinori, A, Arenas Pinto, A, Llibre, J, Amieva, H, Cabie, A, Williams, I, Di Perri, G, Tellez, M, Rockstroh, J, Babiker, A, Pozniak, A, Raffi, F, Richert, L, Dedes, N, Chene, G, Allavena, C, Autran, B, Bucciardini, R, Vella, S, Horban, A, Arribas, J, Boffito, M, Pillay, D, Franquet, X, Schwarze, S, Grarup, J, Fischer, A, Wallet, C, Diallo, A, Molina, J, Saillard, J, Moecklinghoff, C, Stellbrink, H, Leeuwen, R, Gatell, J, Sandstrom, E, Flepp, M, Ewings, F, George, E, Hudson, F, Pearce, G, Quercia, R, Rogatto, F, Leavitt, R, Nguyen, B, Goebel, F, Marcotullio, S, Kaur, N, Sasieni, P, Spencer Drake, C, Peto, T, Miller, V, Arnault, F, Boucherie, C, Jean, D, Paniego, V, Rouch, E, Schwimmer, C, Soussi, M, Taieb, A, Termote, M, Touzeau, G, Cursley, A, Dodds, W, Hoppe, A, Kummeling, I, Pacciarini, F, Paton, N, Russell, C, Taylor, K, Ward, D, Aagaard, B, Eid, M, Gey, D, Jensen, B, Jakobsen, M, Jansson, P, Jensen, K, Joensen, Z, Larsen, E, Pahl, C, Pearson, M, Nielsen, B, Reilev, S, Christ, I, Lathouwers, D, Manting, C, Mendy, B, Metro, A, Couffin Cadiergues, S, Knellwolf, A, Palmisiano, L, Aznar, E, Barea, C, Cotarelo, M, Esteban, H, Girbau, I, Moyano, B, Ramirez, M, Saiz, C, Sanchez, I, Yllescas, M, Binelli, A, Colasanti, V, Massella, M, Anagnostou, O, Gioukari, V, Touloumi, G, Schmied, B, Rieger, A, Vetter, N, Wit, S, Florence, E, Vandekerckhove, L, Gerstoft, J, Mathiesen, L, Katlama, C, Cheret, A, Dupon, M, Ghosn, J, Girard, P, Goujard, C, Levy, Y, Morlat, P, Neau, D, Obadia, M, Perre, P, Piroth, L, Reynes, J, Tattevin, P, Ragnaud, J, Weiss, L, Yazdan, Y, Yeni, P, Zucman, D, Behrens, G, Esser, S, Fatkenheuer, G, Hoffmann, C, Jessen, H, Schmidt, R, Stephan, C, Unger, S, Hatzakis, A, Daikos, G, Papadopoulos, A, Skoutelis, A, Banhegyi, D, Mallon, P, Mulcahy, F, Andreoni, M, Bonora, S, Castelli, F, Monforte, A, Galli, M, Lazzarin, A, Mazzotta, F, Carlo, T, Vullo, V, Prins, J, Richter, C, Verhagen, D, Eeden, A, Doroana, M, Antunes, F, Maltez, F, Sarmento Castro, R, Garcia, J, Aldeguer, J, Clotet, B, Domingo, P, Knobel, H, Marquez, M, Miralles, M, Portilla, J, Soriano, V, Thalme, A, Blaxhult, A, Gisslen, M, Fox, J, Gompels, M, Herieka, E, Johnson, M, Leen, C, Teague, A, Boyd, M, Moller, N, Frosig, E, Moing, V, Wit, F, Kowalska, J, Berenguer, J, Moreno, S, Muhller, N, Torok, E, Post, F, Angus, B, Calvez, V, Boucher, C, Collins, S, Dunn, D, Lambert, S, Marcelin, A, Perno, Cf, White, E, Ammassari, A, Stoehr, W, Odermarsky, M, Smith, C, Thiebaut, R, Laserna, B, Castagna, A, Furrer, H, Mocroft, A, Reiss, P, Fragola, V, Lauriola, M, Murri, R, Nieuwkerk, P, Spire, B, Volny Anne, A, West, B, Maria, J, Braggion, M, Foca, E, Amsterdam institute for Infection and Immunity, Infectious diseases, Global Health, Amsterdam Public Health, Medical Psychology, Winston, A., Stohr, W., Antinori, A., Arenas-Pinto, A., Llibre, J. M., Amieva, H., Cabie, A., Williams, I., Di Perri, G., Tellez, M. J., Rockstroh, J., Babiker, A., Pozniak, A., Raffi, F., Richert, L., on beahlf of NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 Study, Group, and Castagna, A.

Subjects
Gerontology, Male, Antiretroviral naïve, antiretroviral naïve, HIV Infections, 0302 clinical medicine, HIV, antiretroviral naïve, cognitive, neuropsychological tests, Interquartile range, Verbal fluency test, HIV Infection, Pharmacology (medical), 030212 general & internal medicine, Sida, Psychomotor learning, education.field_of_study, biology, NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 Study Group, Health Policy, Cognition, Middle Aged, Settore MED/07 - Microbiologia e Microbiologia Clinica, Cognitive test, Cognitive, Neuropsychological tests, Infectious Diseases, Europe, Anti-Retroviral Agents, Population study, Female, Human, Adult, medicine.medical_specialty, Population, 03 medical and health sciences, Virology, Internal medicine, medicine, Humans, Cognitive Dysfunction, Psychological Tests, education, business.industry, 1103 Clinical Sciences, biology.organism_classification, Psychological Test, neuropsychological test, Anti-Retroviral Agent, business, 030217 neurology & neurosurgery
Abstract

OBJECTIVES: Deficits in cognitive function remain prevalent in HIV-infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in antiretroviral therapy (ART)-naive HIV-infected subjects at the time of enrolment in the NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 study.METHODS: Prior to starting ART, seven cognitive tests exploring domains including episodic memory, verbal fluency, executive function and psychomotor speed were administered with scores standardized to z-score using the study population sample mean and standard deviation. The primary measure was overall z-score average (NPZ). We assessed associations between baseline factors and test results using multivariable regression models.RESULTS: Of 283 subjects with baseline cognitive assessments, 90% were male and 12% of black ethnicity. Median (interquartile range) age, years of education, years of known HIV infection, baseline CD4 count and baseline HIV RNA were 39 (31, 47) years, 13 (11, 17) years, 1 (0, 4) years, 344 (279, 410) cells/μL and 4.74 (4.28, 5.14) log10 HIV-1 RNA copies/mL, respectively. Forty per cent were current smokers. Factors significantly associated with poorer overall cognitive performance in multivariable models included older age, shorter duration of education, black ethnicity, lower height, and lower plasma HIV RNA.CONCLUSIONS: In this large, European-wide, ART-naive population with relatively preserved immunity and early HIV infection, cognitive function scores at the time of ART initiation were associated with demographic and HIV-disease factors. (Less)

Published
2016

14. BEST HOPE - Cohort of HIV newly diagnosed patients in Portugal

Author

Pingarilho, M., Pineda-Peña, A.C., Dias, S., Pimentel, V.F., Libin, P., Aleixo, M.J., Amaral-Alves, D., Ascenção, B., Azevedo, F., Baptista, T., Bredes, C., Brito, P., Cabanas, J., Cabo, J., Caixeiro, M., Caldas, C., Campos, Maria José, Cardoso, S., Carvalho, A.P., Casella, I., Correia, L., Correia-Abreu, R., Côrte-Real, R., Costa, I., Costa, O., Cunha, S., Diogo, I., Faria, D., Faria, T., Feijó, M., Ferreira, J., Germano, I., Gomes, A., Gomes, P., Gonçalves, F., Gonçalves, M.J., Granado, A., Ivo, M.S., Jesus, J., Koch, C., Lino, S., Luís, N., Maio, A., Maltez, F., Mansinho, K., Marques, N., Marques, S., Martins, S., Mateus, E., Mendão, Luís, Messias, C., Monteiro, F., Morais, C., Mota, V., Neves, I., Nunes, S., Oliveira, J., Pacheco, P., Pereira, H., Pereira-Vaz, J., Pessanha, M., Pimenta, A., Piñeiro, C., Pinheiro, S., Pinho, R., Poças, J., Proença, P., Ramos, H., Rocha, Miguel, Rodrigues, C., Rodrigues, P., Rodrigues, R., Roxo, F., Sá, J., Salvado, C., Sarmento-Castro, R., Seixas, D., Serrão, R., Silva, A.R., Silva, E.G., Silva, V., Simão, M., Simões, D., Simões, J., Simões, P., Soares, J., Tavares, R., Teófilo, E., Trigo, D., Theys, K., Martins M.R.O., Vandamme, A.M., Camacho, R.J., and Abecasis AB

Published
2016
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15. Bone mineral density and inflammatory and bone biomarkers after darunavir-ritonavir combined with either raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults with HIV-1: a substudy of the NEAT001/ANRS143 randomised trial

Author

Bernardino, J. I., Mocroft, A., Mallon, P. W., Wallet, C., Gerstoft, J., Russell, C., Reiss, P., Katlama, C., De Wit, S., Richert, L., Babiker, A., Buno, A., Castagna, A., Girard, P. -M., Chene, G., Raffi, F., Arribas, J. R., Dedes, N, Chene, G, Richert, L, Allavena, C, Raffi, F, Autran, B, Antinori, A, Bucciardini, R, Vella, S, Horban, A, Arribas, J, Babiker, Ag, Boffito, M, Pillay, D, Pozniak, A, Franquet, X, Schwarze, S, Grarup, J, Fischer, A, Wallet, C, Diallo, A, Molina, Jm, Saillard, J, Moecklinghoff, C, Stellbrink, Hj, Van Leeuwen, R, Gatell, J, Sandstrom, E, Flepp, M, Ewings, F, George, Ec, Hudson, F, Pearce, G, Quercia, R, Rogatto, F, Leavitt, R, Nguyen, By, Goebel, F, Marcotullio, S, Babiker, A, Kaur, N, Sasieni, P, Spencer-Drake, C, Peto, T, Miller, V, Chêne, G, Arnault, F, Boucherie, C, Jean, D, Paniego, V, Paraina, F, Rouch, E, Schwimmer, C, Soussi, M, Taieb, A, Termote, M, Touzeau, G, Cursley, A, Dodds, W, Hoppe, A, Kummeling, I, Pacciarini, F, Paton, N, Russell, C, Taylor, K, Ward, D, Aagaard, B, Eid, M, Gey, D, Jensen, Bg, Jakobsen, Ml, Jansson, Po, Jensen, K, Joensen, Zm, Larsen, Em, Pahl, C, Pearson, M, Nielsen, Br, Reilev, Ss, Christ, I, Lathouwers, D, Mendy, By, Metro, A, Couffin-Cadiergues, S, Knellwolf, Al, Palmisiano, L, Aznar, E, Barea, C, Cotarelo, M, Esteban, H, Girbau, I, Moyano, B, Ramirez, M, Saiz, C, Sanchez, I, Yllescas, M, Binelli, A, Colasanti, V, Massella, M, Anagnostou, O, Gioukari, V, Touloumi, G, Schmied, B, Rieger, A, Vetter, N, De Wit, S, Florence, E, Vandekerckhove, L, Gerstoft, J, Mathiesen, L, Katlama, C, Cabie, A, Cheret, A, Dupon, M, Ghosn, J, Girard, Pm, Goujard, C, Lévy, Y, Morlat, P, Neau, D, Obadia, M, Perre, P, Piroth, L, Reynes, J, Tattevin, P, Ragnaud, Jm, Weiss, L, Yazdan, Y, Yeni, P, Zucman, D, Behrens, G, Esser, S, Fätkenheuer, G, Hoffmann, C, Jessen, H, Rockstroh, J, Schmidt, R, Stephan, C, Unger, S, Hatzakis, A, Daikos, Gl, Papadopoulos, A, Skoutelis, A, Banhegyi, D, Mallon, P, Mulcahy, F, Andreoni, M, Bonora, S, Castelli, F, Monforte, Ad, Di Perri, G, Galli, M, Lazzarin, A, Mazzotta, F, Carlo, T, Vullo, V, Prins, J, Richter, C, Verhagen, D, Van Eeden, A, Doroana, M, Antunes, F, Maltez, F, Sarmento-Castro, R, Gonzalez Garcia, J, López Aldeguer, J, Clotet, B, Domingo, P, Gatell, Jm, Knobel, H, Marquez, M, Pilar Miralles, M, Portilla, J, Soriano, V, Tellez, Mj, Thalme, A, Blaxhult, A, Gisslen, M, Winston, A, Fox, J, Gompels, M, Herieka, E, Johnson, M, Leen, C, Teague, A, Williams, I, Boyd, Ma, Møller, Nf, Frøsig, E, Larsen, M, Le Moing, V, Wit, Fw, Kowalska, J, Berenguer, J, Moreno, S, Müller, Nj, Török, E, Post, F, Angus, B, Calvez, V, Boucher, C, Collins, S, Dunn, D, Lambert, S, Marcelin, Ag, Perno, Cf, White, E, Ammassari, A, Stoehr, W, Schmidt, Re, Odermarsky, M, Smith, C, Thiébaut, R, De La Serna JI, Castagna, A, Furrer, Hj, Mocroft, A, Reiss, P, Fragola, V, Lauriola, M, Murri, R, Nieuwkerk, P, Spire, B, Volny-Anne, A, West, B, Amieva, H, Codina, Jm, Braggion, Marco, Focà, E, Bernardino Jose, I., Mocroft, Amanda, Mallon Patrick, W., Wallet, Cedrick, Gerstoft, Jan, Russell, Charlotte, Reiss, Peter, Katlama, Christine, De Wit, Stephane, Richert, Laura, Babiker, Abdel, Buno, Antonio, Castagna, Antonella, Girard Pierre, Marie, Chene, Genevieve, Raffi, Francoi, Arribas Jose, R., AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Infectious diseases, and Medical Psychology

Subjects
Male, Bone density, Epidemiology, Infectious Diseases, Immunology, Virology, Osteoporosis, HIV Infections, Comorbidity, Absorptiometry, Photon, Bone Density, Emtricitabine, Darunavir, Middle Aged, Viral Load, Photon, Europe, Osteopetrosis, Combination, Drug Therapy, Combination, Female, Bone Diseases, medicine.drug, Adult, medicine.medical_specialty, Anti-HIV Agents, Biomarkers, Bone Diseases, Metabolic, CD4 Lymphocyte Count, Humans, Inflammation, Raltegravir Potassium, Ritonavir, Tenofovir, Tenofovir alafenamide, Drug Therapy, Internal medicine, medicine, Absorptiometry, business.industry, Abacavir/Lamivudine, Raltegravir, medicine.disease, Surgery, Osteopenia, Regimen, Metabolic, business
Abstract

Osteopenia, osteoporosis, and low bone mineral density are frequent in patients with HIV. We assessed the 96 week loss of bone mineral density associated with a nucleoside or nucleotide reverse transcriptase inhibitor (NtRTI)-sparing regimen. Antiretroviral-naive adults with HIV were enrolled in 78 clinical sites in 15 European countries into a randomised (1:1), open-label, non-inferiority trial (NEAT001/ANRS143) assessing the efficacy and safety of darunavir (800 mg once per day) and ritonavir (100 mg once per day) plus either raltegravir (400 mg twice per day; NtRTI-sparing regimen) or tenofovir (245 mg once per day) and emtricitabine (200 mg once per day; standard regimen). For this bone-health substudy, 20 of the original sites in six countries participated, and any patient enrolled at one of these sites who met the following criteria was eligible: plasma viral loads greater than 1000 HIV RNA copies per mL and CD4 cell counts of fewer than 500 cells per μL, except in those with symptomatic HIV infection. Exclusion criteria included treatment for malignant disease, testing positive for hepatitis B virus surface antigen, pregnancy, creatinine clearance less than 60 mL per min, treatment for osteoporosis, systemic steroids, or oestrogen-replacement therapy. The two primary endpoints were the mean percentage changes in lumbar spine and total hip bone mineral density at week 48, assessed by dual energy x-ray absorptiometry (DXA) scans. We did the analysis with an intention-to-treat-exposed approach with antiretroviral modifications ignored. The parent trial is registered with ClinicalTrials.gov, number NCT01066962, and is closed to new participants. Between Aug 2, 2010, and April 18, 2011, we recruited 146 patients to the substudy, 70 assigned to the NtRTI-sparing regimen and 76 to the standard regimen. DXA data were available for 129, 121 and 107 patients at baseline, 48 and 96 weeks respectively. At week 48, the mean percentage loss in bone mineral density in the lumbar spine was greater in the standard group than in the NtRTI-sparing group (mean percentage change -2.49% vs -1.00%, mean percentage difference -1.49, 95% CI -2.94 to -0.04; p=0.046). Total hip bone mineral density loss was similarly greater at week 48 in the standard group than in the NtRTI-sparing group (mean percentage change -3.30% vs -0.73%; mean percentage difference -2.57, 95% CI -3.75 to -1.35; p

Published
2015

16. Gestão clínica de comorbilidades no envelhecimento da população que vive com VIH: uma revisão de peritos -- Parte I.

Author

Horta, A., Marques, N., Ferreira, A., Carneiro, F., Massano, J., Ferreira, J., Bragança, M., Tomada, N., Freitas, P., Maltez, F., Saraiva da Cunha, J., and Sarmento Castro, R.

Abstract

Copyright of RPDI - Revista Portuguesa de Doenças Infecciosas is the property of Sociedade Portuguesa de Doencas Infecciosas e Microbiologia Clinica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2019

17. Hepatite C em toxicodependentes: acompanhamento e acesso à terapêutica

Author

Sarmento-Castro, R., Valente, C., Ramos, J., Almeida, J., Marinho, R., Branco, T., Andrade, S., and Macedo, A.

Subjects
Hepatite C, Portugal, Abuso de substâncias por via intravenosa, Normas de orientação clínica
Abstract

A hepatite C constitui, actualmente, um grave problema de saúde pública. Estima-se que existam, em todo o mundo, 180 milhões de pessoas com infecção crónica por vírus da hepatite C (VHC) e que a sua prevalência na população portuguesa varie entre 1 e 1,5%. Em Portugal, não existem normas de orientação actualizadas de tratamento, nem recomendações para o diagnóstico e acompanhamento dos doentes com VHC e, em particular, para os UDEVs. O presente artigo reúne informação de consenso relativa à de prática clínica e propõe algumas orientações para o acompanhamento e acessibilidade ao tratamento dos doentes toxicodependentes com infecção crónica por VHC, em Portugal.

Published
2011

19. Linfoma Pulmonar Primário relacionado com infeção por VIH.

Author

Martins, S., Quinaz, C., Xará, S., Vasconcelos, O., Vicente, P., and Sarmento-Castro, R.

Abstract

Copyright of RPDI - Revista Portuguesa de Doenças Infecciosas is the property of Sociedade Portuguesa de Doencas Infecciosas e Microbiologia Clinica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2017

21. Glycaemic profile changes by highly active antiretroviral therapy in human immunodeficiency virus-infected patients.

Author

Duro, M, Rebelo, I, Barreira, S, Sarmento-Castro, R, Medeiros, R, and Almeida, C

Subjects
DIAGNOSIS of diabetes, HIV infection complications, ANTI-HIV agents, BLOOD sugar, DIABETES, GLUCOSE tolerance tests, HIV, LONGITUDINAL method, RNA, VIRAL load, BODY mass index, HIGHLY active antiretroviral therapy, RETROSPECTIVE studies, CD4 lymphocyte count, MIXED infections
Abstract

To study dysglycaemia in human immunodeficiency virus (HIV)-infected patients we conducted a retrospective cohort study of the glucose profile in HIV-infected patients. The fasting blood glucose was analysed taking into consideration conventional risk factors as well as HIV infection and highly active antiretroviral therapy (HAART). One hundred seventy-three cases were selected for this study. Five risk factors had significant effects (p < 0.05) on glucose levels: age, body mass index (BMI), hepatitis C virus/hepatitis B virus (HCV/HBV) co-infection, viral load (VL), and CD4(+) T-lymphocyte count. Fasting blood glucose levels increased with age (0.59 mg/dL/year), decreased with the VL (-4.1 × 10(-6 )mg/dL/number of viral RNA copies) and the CD4(+) T-lymphocyte count (-0.016 mg/dL/cell count). Furthermore, obese patients and those co-infected with HCV/HBV were more prone to develop dysglycaemia having, on average, 15.4 mg/dL and 13.8 mg/dL higher levels, respectively, of fasting blood glucose. Despite an increase of 1.0% and 8.4% in the glucose levels noticed among HIV patients treated with non-nucleotide inhibitors of reverse transcriptase and protease inhibitors, respectively, HAART did not prove to be a significant predictor of fasting glucose levels as well as lipodystrophy and male gender. Age, BMI, HCV/HBV co-infection and HIV-related (VL and CD4(+) T-lymphocyte count) factors seem to be the most influential on fasting blood glucose levels in HIV-infected individuals. [ABSTRACT FROM AUTHOR]

Published
2015
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22. Efficacy, safety and tolerability of enfuvirtide in a population of Portuguese HIV-1 chronically infected patients

Author

Miranda, AC, primary, Almeida, I, additional, Mendez, J, additional, Mota, M, additional, Teofilo, E, additional, Vera, J, additional, Diniz, A, additional, Maltez, F, additional, Marques, R, additional, Mansinho, K, additional, Sarmento-Castro, R, additional, Camacho, R, additional, Manata, MJ, additional, and Delgado, C, additional

Published
2008
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23. Hipertensão portal não-cirrótica e uso de Didanosina. A propósito de um caso clínico.

Author

Almeida, S., Vasconcelos, O., Pedroto, I., and Sarmento-Castro, R.

Abstract

Copyright of RPDI - Revista Portuguesa de Doenças Infecciosas is the property of Sociedade Portuguesa de Doencas Infecciosas e Microbiologia Clinica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2012

24. Tuberculose em doentes com Sida. Tratamento completo sob observação directa##Projecto de investigação subsidiado pela Comissão Nacional de Luta Contra a SIDA

Author

Sarmento-Castro, R., Sousa Barros, A., Gonzalez, J., Rocha-Marques, Veloso, S., Terceiro, M., Costa, C., Horta, A., Forte, O., Vasconcelos, O., Coelho, H., Vasconcelos, A.L., Viegas, E., Recalde, C., and Braga, J.

Abstract

A co-infecção VIH-tuberculose tem um enorme impacto em termos de saúde pública. A deficiente adesão ao tratamento antibacilar, particularmente em toxicodependentes infectados por VIH, contribui para a elevada morbilidade e mortalidade registadas e, bem assim, para o recrudescimento da multirresistência da bacilo da tuberculose e para a sua disseminação na comunidade.

Published
2001
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25. Global prevalence and genotype distribution of hepatitis C virus infection in 2015:a modelling study

Author

Hans Van Vlierberghe, Soo Aleman, Naveed Z. Janjua, Henry Lik-Yuen Chan, Olufunmilayo A. Lesi, Irena Hrstić, Abdullah M. Assiri, William Rosenberg, Moon sing Lai, Vladimir Chulanov, Jan Sperl, Beat Müllhaupt, Michael Manns, William Sievert, Sabahattin Kaymakoglu, Cesar Yaghi, Evy Yunihastuti, Pierre Van Damme, Jon G. Jonasson, Antonio Javier Blasco, Young Sik Kim, S. Olafsson, Rohani Jahis, Christoph Sarrazin, Manik Sharma, Aasim Yusuf, Omer Hajelssedig, Javier García-Samaniego, Boris Lukšić, Peter Stärkel, Stefan Zeuzem, Stephen Oguche, E. A. Croes, Abdullah S. Alghamdi, Richard Njouom, CE Omuemu, Carlos E Brandão Mello, Adam Mahomed, Behzad Hajarizadeh, Ogu Omede, Said A. Al-Busafi, Sarah Robbins, Peer Brehm Christensen, Ammal M. Metwally, Béla Hunyady, Gamal Esmat, Ivane Gamkrelidze, Maheeba Abdulla, Suzanne Norris, Sarah Blach, Harald Hofer, Maria C Mendes Correa, Devin Razavi-Shearer, Matti Maimets, Chien-Jen Chen, Peter Jarcuska, Marian Oltman, Francesco Negro, Ilias Gountas, Ayman Yosry, Sona Frankova, Adrian Goldis, Laurentius A. Lesmana, Ivan Schréter, Danute Speiciene, Kevork M. Peltekian, Berhane Redae, Stuart K. Roberts, Valentina Liakina, Seyed M Alavian, Wai-cheung C Lao, Ziv Ben-Ari, Imad Al Ghazzawi, Cheryl Brunton, Rudolf E. Stauber, Akram Khan, Tung-Hung Su, Manal H El-Sayed, Kimberly Murphy, Kyriakos Souliotis, Adriana Vince, Ramazan Idilman, Christophe Moreno, Angelos Hatzakis, Lewis R. Roberts, Richard Phillips, Jason Grebely, Michael Gschwantler, Hugo Cheinquer, Vana Sypsa, Samir Shah, Wolfgang Vogel, M. Blachier, Abate Bane, Henri Leleu, Saeed Hamid, Ohene Opare-Sem, Hamad Al-Romaihi, Wan-Long Chuang, Alexander J. Thompson, Agita Jeruma, Robert Flisiak, Catherine A.M. Stedman, Ingo van Thiel, Carole Seguin-Devaux, Jonathan Schmelzer, Juan F.Sanchez Avila, Rui Tato Marinho, Muhammad S. Memon, Nina Weis, Rosmawati Mohamed, Florian Bihl, Moon Seok Choi, David Kershenobich, Vic Arendt, Yee Tak Hui, Mei Hsuan Lee, N. N. Pimenov, Saad Al Kaabi, Ken Pasini, Henrik Krarup, Stefan Mauss, Shahin Merat, Khalid Al Namaani, Rong-Nan Chien, Perttu Arkkila, Henk W. Reesink, Françoise Roudot-Thoraval, Paul Marotta, Shirley Owusu-Ofori, Fadi H. Mourad, Abdul Rahman Bizri, Chris Estes, Heiner Wedemeyer, Faisal M. Sanai, Mihály Makara, Stephen D. Ryder, Mel Krajden, Laura Cisneros, Adriaan J. van der Meer, Eli Zuckerman, Matthew E. Cramp, Rui Sarmento-Castro, Magnus Gottfredsson, Gregory J. Dore, Huma Qureshi, Yasser Kamel, Olga Sagalova, Rifaat Safadi, Wim Laleman, Solomon Obekpa, Karolin Falconer, Edward Gane, Philip Bruggmann, Fernando Bessone, Jia-Horng Kao, Daniel Lavanchy, Riina Salupere, Anne Øvrehus, Ulus Salih Akarca, Monique Andersson, Man-Fung Yuen, Ala I. Sharara, Olav Dalgard, Homie Razavi, Gamal Shiha, Paulo R. Ferreira, George V. Papatheodoridis, Anatoly Shevaldin, Jawad Khamis, Waseem Hamoudi, Kathryn Razavi-Shearer, Vincent Ws Wong, Loreta A. Kondili, Maria Lucia Gomes Ferraz, Wasim Jafri, Pablo Lázaro, Faisal Abaalkhail, David H. Muljono, Youssif Al Serkal, Imam Waked, Zaher Koutoubi, Oidov Baatarkhuu, Nahum Méndez-Sánchez, Abraham O. Malu, Daniel Struck, Helen Nde, Alnoor Ramji, Ahmed Abdou, Antoine Abou Rached, Michael Li, Diana Nonković, Jorge Daruich, Ezequiel Ridruejo, Gül Ergör, Ann-Sofi Duberg, Krzysztof Tomasiewicz, Filipe Calinas, Hossein Poustchi, Layla Al-Dabal, Jessie Gunter, Mark W. Sonderup, Colm Bergin, Mario G. Pessoa, Jonas Valantinas, Asad Chaudhry, Junko Tanaka, Tsendsuren S. Oyunsuren, Soek Siam Tan, Vivek A. Saraswat, Young-Suk Lim, Ibrahim Altraif, Victor de Ledinghen, Faryal Al Lawati, Mette Rye Clausen, Ieva Tolmane, Antonio Craxì, Abdulrahman Aljumah, Elmoubashar Farag, Inka Aho, Sayed Himatt, Nishi Prabdial-Sing, Blach S., Zeuzem S., Manns M., Altraif I., Duberg A.-S., Muljono D.H., Waked I., Alavian S.M., Lee M.-H., Negro F., Abaalkhail F., Abdou A., Abdulla M., Abou Rached A., Aho I., Akarca U., Al Ghazzawi I., Al Kaabi S., Al Lawati F., Al Namaani K., Al Serkal Y., Al-Busafi S.A., Al-Dabal L., Aleman S., Alghamdi A.S., Aljumah A.A., Al-Romaihi H.E., Andersson M.I., Arendt V., Arkkila P., Assiri A.M., Baatarkhuu O., Bane A., Ben-Ari Z., Bergin C., Bessone F., Bihl F., Bizri A.R., Blachier M., Blasco A.J., Brandao Mello C.E., Bruggmann P., Brunton C.R., Calinas F., Chan H.L.Y., Chaudhry A., Cheinquer H., Chen C.-J., Chien R.-N., Choi M.S., Christensen P.B., Chuang W.-L., Chulanov V., Cisneros L., Clausen M.R., Cramp M.E., Craxi A., Croes E.A., Dalgard O., Daruich J.R., De Ledinghen V., Dore G.J., El-Sayed M.H., Ergor G., Esmat G., Estes C., Falconer K., Farag E., Ferraz M.L.G., Ferreira P.R., Flisiak R., Frankova S., Gamkrelidze I., Gane E., Garcia-Samaniego J., Khan A.G., Gountas I., Goldis A., Gottfredsson M., Grebely J., Gschwantler M., Guimaraes Pessoa M., Gunter J., Hajarizadeh B., Hajelssedig O., Hamid S., Hamoudi W., Hatzakis A., Himatt S.M., Hofer H., Hrstic I., Hui Y.-T., Hunyady B., Idilman R., Jafri W., Jahis R., Janjua N.Z., Jarcuska P., Jeruma A., Jonasson J.G., Kamel Y., Kao J.-H., Kaymakoglu S., Kershenobich D., Khamis J., Kim Y.S., Kondili L., Koutoubi Z., Krajden M., Krarup H., Lai M.-S., Laleman W., Lao W.-C., Lavanchy D., Lazaro P., Leleu H., Lesi O., Lesmana L.A., Li M., Liakina V., Lim Y.-S., Luksic B., Mahomed A., Maimets M., Makara M., Malu A.O., Marinho R.T., Marotta P., Mauss S., Memon M.S., Mendes Correa M.C., Mendez-Sanchez N., Merat S., Metwally A.M., Mohamed R., Moreno C., Mourad F.H., Mullhaupt B., Murphy K., Nde H., Njouom R., Nonkovic D., Norris S., Obekpa S., Oguche S., Olafsson S., Oltman M., Omede O., Omuemu C., Opare-Sem O., Ovrehus A.L.H., Owusu-Ofori S., Oyunsuren T.S., Papatheodoridis G., Pasini K., Peltekian K.M., Phillips R.O., Pimenov N., Poustchi H., Prabdial-Sing N., Qureshi H., Ramji A., Razavi-Shearer D., Razavi-Shearer K., Redae B., Reesink H.W., Ridruejo E., Robbins S., Roberts L.R., Roberts S.K., Rosenberg W.M., Roudot-Thoraval F., Ryder S.D., Safadi R., Sagalova O., Salupere R., Sanai F.M., Sanchez Avila J.F., Saraswat V., Sarmento-Castro R., Sarrazin C., Schmelzer J.D., Schreter I., Seguin-Devaux C., Shah S.R., Sharara A.I., Sharma M., Shevaldin A., Shiha G.E., Sievert W., Sonderup M., Souliotis K., Speiciene D., Sperl J., Starkel P., Stauber R.E., Stedman C., Struck D., Su T.-H., Sypsa V., Tan S.-S., Tanaka J., Thompson A.J., Tolmane I., Tomasiewicz K., Valantinas J., Van Damme P., Van Der Meer A.J., Van Thiel I., Van Vlierberghe H., Vince A., Vogel W., Wedemeyer H., Weis N., Wong V.W.S., Yaghi C., Yosry A., Yuen M.-F., Yunihastuti E., Yusuf A., Zuckerman E., Razavi H., Polaris Observ HCV Collaborators, Negro, Francesco, and Ege Üniversitesi

Subjects
Viremia/epidemiology, Population ageing, medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, Delphi Technique, Genotype, Voxilaprevir, Genotype, Global Health, Hepatitis C, Eradication, Modelling study, Medicina Clínica, ddc:616.07, Global Health, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Cost of Illness, Epidemiology, Journal Article, medicine, Global health, Prevalence, Humans, Viremia, 030212 general & internal medicine, Disease Eradication, Disease burden, ddc:616, Hepatology, Hepatitis C, Chronic/epidemiology, business.industry, Gastroenterology, Hepatitis C, Glecaprevir, Hepatitis C, Chronic, medicine.disease, Viremia/epidemiology/genetics, Pibrentasvir, Global Health/statistics & numerical data, HCV, HEPATITIS C, 030211 gastroenterology & hepatology, Medicina Critica y de Emergencia, Human medicine, business, Chronic/epidemiology/genetics/prevention & control, Demography
Abstract

WOS: 000426979400014, PubMed ID: 28404132, Background The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of-and expansion on-the 2014 analysis, which reported 80 million (95% CI 64-103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1.0% (95% uncertainty interval 0.8-1.1) in 2015, corresponding to 71.1 million (62.5-79.4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections., John C Martin Foundation, John C Martin Foundation.

Published
2017

26. [Guideline for the Treatment and Prevention of Infections Associated with Immunosuppressive Therapy for Autoimmune Diseases].

Author

Valdoleiros SR, Furtado I, Silva C, Correia Gonçalves I, Santos Silva A, Vasconcelos O, Aboim Horta A, Vasconcelos AL, Xará S, Gonçalves MJ, Araújo Abreu M, and Sarmento-Castro R

Subjects
Humans, Immune Tolerance, Immunomodulation, Immunosuppressive Agents, Autoimmune Diseases drug therapy, Immunosuppression Therapy
Abstract

We propose a guideline about the risk, prevention and treatment of infection in the patient under immunomodulatory or immunosuppressive therapy in the context of autoimmune or autoinflammatory disease. It is divided into three sections: drugs and associated risk of infection; immunizations; risk, prevention, and treatment of specific infections. The treatment of autoimmune diseases involves the use of immunosuppressive or immunomodulatory therapies, with an increasing number of new drugs being used. It is associated with an increased risk of infection, which may be present globally or only for specific agents, varying widely depending on the pharmacological class and even within the same class. The prevention strategy and clinical management need to be individually tailored and there are several key factors: characterization of the disease that prompts the immunosuppression, understanding of the mechanism of action of the immunosuppressive drug, knowledge of previous infections, recognition of risk factors, laboratory test results, vaccine administration, monitoring of clinical signs and symptoms and patient education.

Published
2021
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27. Impact of Liver Test Abnormalities and Chronic Liver Disease on the Clinical Outcomes of Patients Hospitalized with COVID-19.

Author

Garrido M, Pereira Guedes T, Alves Silva J, Falcão D, Novo I, Archer S, Rocha M, Maia L, Sarmento-Castro R, and Pedroto I

Abstract

Background and Aims: The impact of SARS-CoV-2 infection on the liver and the possibility of chronic liver disease (CLD) as a risk factor for COVID-19 severity is not fully understood. Our goal was to describe clinical outcomes of COVID-19 inpatients regarding the presence of abnormal liver tests and CLD., Methods: A retrospective analysis of patients with SARS-CoV-2 infection, hospitalized in a tertiary center in Portugal, was performed. Studied outcomes were disease and hospitalization length, COVID-19 severity, admission to intensive care unit (ICU) and mortality, analyzed by the presence of abnormal liver tests and CLD., Results: We included 317 inpatients with a mean age of 70.4 years, 50.5% males. COVID-19 severity was moderate to severe in 57.4% and critical in 12.9%. The mean disease length was 37.8 days, the median hospitalization duration 10.0 days and overall mortality 22.8%. At admission, 50.3% showed abnormal liver tests, and 41.5% showed elevated aminotransferase levels, from which 75.4% were mild. Elevated aminotransferase levels at admission were associated with COVID-19 severity (78.7 vs. 63.3%, p = 0.01), ICU admission (13.1 vs. 5.92%, p = 0.034) and increased mortality (25.8 vs. 13.3%, p = 0.007). However, in a subgroup analysis, only aspartate transaminase (AST) was associated with these worse outcomes. Alkaline phosphatase was elevated in 11.4% of the patients and was associated with critical COVID-19 (21.1 vs. 9.92%, p = 0.044) and mortality (20.4 vs. 9.52%, p = 0.025), while 24.6% of the patients showed elevated γ-glutamyl transferase, which was associated with ICU admission (42.3 vs. 22.8%, p = 0.028). Fourteen patients had baseline CLD (4.42%), 3 with liver cirrhosis. Alcohol ( n = 6) and nonalcoholic fatty liver disease ( n = 6) were the most frequent etiologies. CLD patients had critical COVID-19 in 21.4% ( p = 0.237), mean disease length of 36.6 days ( p = 0.291), median hospitalization duration of 11.5 days ( p = 0.447) and a mortality rate of 28.6% ( p = 0.595), which increased to 66.7% among cirrhotic patients ( p = 0.176)., Conclusions: Liver test abnormalities in COVID-19 patients were frequent but most commonly mild. AST, but not alanine transaminase, was associated with worse clinical outcomes, such as COVID-19 severity and mortality, probably indicating these outcomes were independent of liver injury. A low prevalence of CLD was seen, and a clear impact on COVID-19 outcomes was not seen., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by Sociedade Portuguesa de Gastrenterologia Published by S. Karger AG, Basel.)

Published
2021
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28. Oral ulcer as presentation of cavitating pulmonary tuberculosis.

Author

Fragoso J, Oliveira MM, Gonçalves C, Méndez J, and Sarmento-Castro R

Abstract

Tuberculosis is an indolent infection that can invade any organ. Although the most frequent form of presentation is pulmonary, it can have an extra-pulmonary presentation, including rare cases of oral tuberculosis. We present a clinical case of a 44 year-old man, active smoker, with an ulcerated lesion on the posterior third of the tongue, initially interpreted as a probable neoplasm. The pathological study of the biopsy performed on the lesion, showed alterations compatible with a chronic granulomatous process and the presence of acid-fast bacilli. The concomitant diagnosis of pulmonary tuberculosis was made in a subsequent study. The patient started therapy with isoniazid, rifampin, pyrazinamide and ethambutol with complete resolution of the oral lesion and pulmonary tuberculosis. This case exemplifies the importance of including tuberculosis in the differential diagnosis of ulcerated and neoformative lesions and the value of performing a microbiological study alongside the pathological one., (© 2020 The Authors. Published by Elsevier Ltd.)

Published
2020
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29. Chronic hepatitis C treatment in HIV co-infection in Portugal: Results from a cohort OF 2133 patients presented by GEPCOI (Portuguese Coinfection Study Group).

Author

Miranda AC, Mendez J, Serrão R, Vale F, Manata MJ, Pinto S, Gomes A, Valente C, Pacheco P, Pazos R, Pereira R, Martins A, Germano I, Rocha S, Reis AP, and Sarmento-Castro R

Subjects
Adult, Aged, Drug Therapy, Combination, Female, Genotype, Hepacivirus, Humans, Male, Middle Aged, Nigeria, Portugal, Quality of Life, Sofosbuvir therapeutic use, Treatment Outcome, Young Adult, Antiviral Agents therapeutic use, Coinfection drug therapy, HIV Infections drug therapy, Hepatitis C, Chronic drug therapy
Abstract

Direct-acting antiviral drugs (DAAs) have recently changed the paradigm of hepatitis C therapy, significantly improving treatment response rates, patient life expectancy and quality of life. In Portugal, sofosbuvir (SOF) and SOF/ledipasvir (SOF/LDV) were fully reimbursed by the National Health System since early 2015 and generalized use of interferon-free DAA based regimens became current practice. During 2016, the remaining DAAs were sequentially added and covered by the same health access policy. The Portuguese Study Group of Hepatitis and HIV Co-infection (GEPCOI) collected data from 15 clinical centres in Portugal, pertaining to the HCV treatment experience with DAA regimens. A cohort of 2133 patients was analysed, representing one of the largest DAA treated HCV/HIV co-infected individuals. The global sustained virologic response (SVR) achieved was 95% in this real-life cohort setting. Linear regression analysis showed significant differences in treatment response rates when using SOF plus ribavirin (RBV) combination in genotype 2 or 3 infected individuals (P < .002) and in those with liver cirrhosis (P < .002). These findings corroborate that early treatment is mandatory in HIV/HCV co-infected patients, as response rates may be negatively influenced by higher fibrosis stages and suboptimal DAA regimens. The current national Portuguese health policy should continue to promote wider treatment access and individualized therapy strategies, aiming at the elimination of HCV infection in this high-risk co-infected population., (© 2020 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Published
2020
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30. Nontravel-related invasive Entamoeba histolytica infection with probable heterosexual transmission.

Author

R de Valdoleiros S, Abranches Carvalho J, Gonçalves C, Vasconcelos O, and Sarmento-Castro R

Abstract

Introduction: In industrialized countries, amebiasis usually occurs in migrants and travelers returning from areas where the disease is endemic, primarily by ingestion of contaminated food or water. Person-to-person transmission can occur, mainly by fecal-oral contact, but sexual transmission has also been described [1,[3], [4], [5]]., Presentation of Case: We report a man with Entamoeba histolytica colitis and a large liver abscess (16.5 × 14 cm) in Portugal, who had no relevant travel history and whose only risk factor was his heterosexual partner. The abscess required drainage of 1950 mL of "chocolate-milk" purulent fluid, with rapid symptomatic improvement. The diagnosis was established by real-time reverse transcription PCR for Entamoeba histolytica in the liver aspirate, with positive IgG antibodies. He received a total of 16 days of ceftriaxone and metronidazole followed by 7 days of paromomycin., Conclusion: As enteric infections may be sexually transmitted, in industrialized countries, even in the absence of travel, sexual history should not be neglected.

Published
2019
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31. Benefit of Early versus Deferred Antiretroviral Therapy on Progression of Liver Fibrosis among People with HIV in the START Randomized Trial.

Author

Dharan NJ, Neuhaus J, Rockstroh JK, Peters L, Gordin F, Arenas-Pinto A, Emerson C, Marks K, Hidalgo J, Sarmento-Castro R, Stephan C, Kumarasamy N, Emery S, and Matthews GV

Subjects
Adult, Cohort Studies, Disease Progression, Early Medical Intervention, Female, Humans, Male, Time-to-Treatment, Anti-Retroviral Agents therapeutic use, HIV Infections complications, HIV Infections drug therapy, Liver Cirrhosis etiology
Abstract

The role of antiretroviral therapy (ART) in reducing or contributing to liver fibrosis in persons with human immunodeficiency virus (HIV) is unclear. We evaluated participants in the Strategic Timing of AntiRetroviral Treatment (START) trial for liver fibrosis using the AST to Platelet Ratio Index (APRI) and Fibrosis-4 Index (FIB-4), and assessed for a benefit of early versus delayed ART on liver fibrosis progression. ART-naïve persons with high CD4 counts (>500 cells/µL) from 222 clinical sites in 35 countries were randomized to receive ART either at study enrollment (immediate treatment arm) or when their CD4 count fell below 350 cells/µL (deferred treatment arm). The following outcomes were evaluated: fibrosis (APRI > 0.5 or FIB-4 > 1.45), significant fibrosis (APRI > 1.5 or FIB-4 > 3.25), hepatic flare, and resolution of elevated APRI and FIB-4 scores. Of the 4,684 enrolled into the START study, 104 did not have APRI or FIB-4 results and were excluded. Among 4,580 participants (2,273 immediate treatment; 2,307 deferred treatment), the median age was 36 years, 26.9% were female, and 30.4% were black. Three percent had an alcoholism or substance abuse history, 6.4% had hepatitis B and/or C, and 1.1% had significant fibrosis at baseline. The median CD4 count was 651, and 5.3% had HIV RNA ≤ 200. Immediate arm participants were at lower risk of developing increased fibrosis scores than deferred arm participants (hazard ratio [HR] = 0.66; 95% confidence interval [CI] = 0.57-0.78; P < 0.001) and more likely to have resolution of elevated baseline scores (HR 1.6; 95% CI 1.3-1.9; P < 0.001). Conclusions: Significant liver fibrosis was rare among ART-naïve HIV-positive persons with high CD4 counts. Our findings suggest a benefit of early ART in preventing the development of liver fibrosis., (© 2018 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases.)

Published
2019
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32. [Late Neuroborreliosis in an Erasmus Programme Student].

Author

Santos FV, Cipriano A, Abreu MA, Andrade C, and Sarmento-Castro R

Subjects
Belgium ethnology, Humans, Male, Portugal, Young Adult, Lyme Neuroborreliosis diagnosis, Lyme Neuroborreliosis drug therapy
Abstract

Lyme disease is an endemic zoonosis, the most prevalent tick-transmitted infection in temperate areas of Europe, North America and Asia. It is a multisystemic disease with cutaneous, musculoskeletal, neurologic and cardiac manifestations, according to the stage of the disease. We describe a case of late neuroborreliosis in an Erasmus programme student living in Porto. We discuss the importance of the epidemiological suspicion, the clinical approach, the diagnostic criteria and the most adequate treatment.

Published
2018
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33. Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets.

Author

Rb-Silva R, Nobrega C, Reiriz E, Almeida S, Sarmento-Castro R, Correia-Neves M, and Horta A

Subjects
Acquired Immunodeficiency Syndrome complications, Acquired Immunodeficiency Syndrome drug therapy, Adult, Anti-HIV Agents adverse effects, Antiprotozoal Agents therapeutic use, Antiretroviral Therapy, Highly Active adverse effects, Brain diagnostic imaging, Central Nervous System Diseases chemically induced, Central Nervous System Diseases diagnostic imaging, HIV Infections immunology, Humans, Immune Reconstitution Inflammatory Syndrome chemically induced, Immune Reconstitution Inflammatory Syndrome diagnostic imaging, Longitudinal Studies, Magnetic Resonance Imaging, Male, Spinal Cord diagnostic imaging, T-Lymphocyte Subsets immunology, Tomography, X-Ray Computed, Toxoplasmosis, Cerebral complications, Toxoplasmosis, Cerebral diagnostic imaging, Toxoplasmosis, Cerebral drug therapy, Acquired Immunodeficiency Syndrome immunology, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Central Nervous System Diseases immunology, Immune Reconstitution Inflammatory Syndrome immunology, Toxoplasmosis, Cerebral immunology
Abstract

Background: HIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality. Hence, a deeper knowledge of CNS-IRIS pathogenesis is needed., Case Presentation: A 37-year-old man was diagnosed with AIDS and cerebral toxoplasmosis. Anti-toxoplasma treatment was initiated immediately, followed by active antiretroviral therapy (HAART) 1 month later. At 2 months of HAART, he presented with progressive hyposensitivity of the right lower limb associated with brain and dorsal spinal cord lesions, compatible with paradoxical toxoplasmosis-associated CNS-IRIS, a condition with very few reported cases. A stereotactic biopsy was planned but was postponed based on its inherent risks. Patient showed clinical improvement with no requirement of corticosteroid therapy. Routine laboratorial analysis was complemented with longitudinal evaluation of blood T cell subsets at 0, 1, 2, 3 and 6 months upon HAART initiation. A control group composed by 9 HIV-infected patients from the same hospital but with no IRIS was analysed for comparison. The CNS-IRIS patient showed lower percentage of memory CD4 + T cells and higher percentage of activated CD4 + T cells at HAART initiation. The percentage of memory CD4 + T cells drastically increased at 1 month after HAART initiation and became higher in comparison to the control group until clinical recovery onset; the percentage of memory CD8 + T cells was consistently lower throughout follow-up. Interestingly, the percentage of regulatory T cells (Treg) on the CNS-IRIS patient reached a minimum around 1 month before symptoms onset., Conclusion: Although both stereotactic biopsies and steroid therapy might be of use in CNS-IRIS cases and should be considered for these patients, they might be unnecessary to achieve clinical improvement as shown in this case. Immunological characterization of more CNS-IRIS cases is essential to shed some light on the pathogenesis of this condition.

Published
2017
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34. A Prediction Rule to Stratify Mortality Risk of Patients with Pulmonary Tuberculosis.

Author

Bastos HN, Osório NS, Castro AG, Ramos A, Carvalho T, Meira L, Araújo D, Almeida L, Boaventura R, Fragata P, Chaves C, Costa P, Portela M, Ferreira I, Magalhães SP, Rodrigues F, Sarmento-Castro R, Duarte R, Guimarães JT, and Saraiva M

Subjects
Adult, Cohort Studies, Female, Humans, Male, Middle Aged, Risk Factors, Tuberculosis, Pulmonary mortality
Abstract

Tuberculosis imposes high human and economic tolls, including in Europe. This study was conducted to develop a severity assessment tool for stratifying mortality risk in pulmonary tuberculosis (PTB) patients. A derivation cohort of 681 PTB cases was retrospectively reviewed to generate a model based on multiple logistic regression analysis of prognostic variables with 6-month mortality as the outcome measure. A clinical scoring system was developed and tested against a validation cohort of 103 patients. Five risk features were selected for the prediction model: hypoxemic respiratory failure (OR 4.7, 95% CI 2.8-7.9), age ≥50 years (OR 2.9, 95% CI 1.7-4.8), bilateral lung involvement (OR 2.5, 95% CI 1.4-4.4), ≥1 significant comorbidity-HIV infection, diabetes mellitus, liver failure or cirrhosis, congestive heart failure and chronic respiratory disease-(OR 2.3, 95% CI 1.3-3.8), and hemoglobin <12 g/dL (OR 1.8, 95% CI 1.1-3.1). A tuberculosis risk assessment tool (TReAT) was developed, stratifying patients with low (score ≤2), moderate (score 3-5) and high (score ≥6) mortality risk. The mortality associated with each group was 2.9%, 22.9% and 53.9%, respectively. The model performed equally well in the validation cohort. We provide a new, easy-to-use clinical scoring system to identify PTB patients with high-mortality risk in settings with good healthcare access, helping clinicians to decide which patients are in need of closer medical care during treatment., Competing Interests: The authors have declared that no competing interests exist.

Published
2016
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35. Longitudinal evaluation of regulatory T-cell dynamics on HIV-infected individuals during the first 2 years of therapy.

Author

Nobrega C, Horta A, Coutinho-Teixeira V, Martins-Ribeiro A, Baldaia A, Rb-Silva R, Santos CL, Sarmento-Castro R, and Correia-Neves M

Subjects
Adult, Aged, Anti-Retroviral Agents therapeutic use, CD4 Lymphocyte Count, Female, HIV Infections drug therapy, Humans, Longitudinal Studies, Male, Middle Aged, Time Factors, Young Adult, HIV Infections pathology, Immunity, Cellular, T-Lymphocyte Subsets immunology, T-Lymphocytes, Regulatory immunology
Abstract

Objectives: A sizeable percentage of individuals infected by HIV and on antiretroviral therapy (ART) fail to increase their CD4 T-cells to satisfactory levels. The percentage of regulatory T-cells (Tregs) has been suggested to contribute to this impairment. This study aimed to address this question and to expand the analysis of Tregs subpopulations during ART., Design: Longitudinal follow-up of 81 HIV-infected individuals during the first 24 months on ART., Methods: CD4 T-cell counts, Tregs percentages, and specific Tregs subpopulations were evaluated at ART onset, 2, 6, 9, 12, 16, 20, and 24 months of ART (five individuals had no Tregs information at baseline)., Results: The slope of CD4 T-cell recovery was similar for individuals with moderate and with severe lymphopenia at ART onset. No evidence was found for a contribution of the baseline Tregs percentages on the CD4 T-cell counts recovery throughout ART. In comparison to uninfected individuals, Tregs percentages were higher at ART onset only for patients with less than 200 cells/μl at baseline and decreased afterwards reaching normal values. Within Tregs, the percentage of naive cells remained low in these patients. Reduced thymic export and increased proliferation of Tregs vs. conventional CD4 T cells might explain these persistent alterations., Conclusion: No effect of Tregs percentages at baseline was detected on CD4 T-cell recovery. However, profound alterations on Tregs subpopulations were consistently observed throughout ART for patients with severe lymphopenia at ART onset.

Published
2016
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36. Poor immune reconstitution in HIV-infected patients associates with high percentage of regulatory CD4+ T cells.

Author

Horta A, Nobrega C, Amorim-Machado P, Coutinho-Teixeira V, Barreira-Silva P, Boavida S, Costa P, Sarmento-Castro R, Castro AG, and Correia-Neves M

Subjects
Adult, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, Antigens, CD genetics, Antigens, CD immunology, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Case-Control Studies, Female, HIV Infections drug therapy, HIV Infections pathology, HIV Infections virology, Humans, Immunologic Memory drug effects, Immunophenotyping, Lymphocyte Activation drug effects, Male, Middle Aged, T-Lymphocytes, Cytotoxic pathology, T-Lymphocytes, Cytotoxic virology, T-Lymphocytes, Regulatory pathology, T-Lymphocytes, Regulatory virology, Viral Load drug effects, HIV Infections immunology, HIV-1 immunology, T-Lymphocytes, Cytotoxic immunology, T-Lymphocytes, Regulatory immunology
Abstract

CD4(+) regulatory T cells (Tregs) are essential for the maintenance of the immune system's equilibrium, by dampening the activation of potential auto-reactive T cells and avoiding excessive immune activation. To correctly perform their function, Tregs must be maintained at the right proportion with respect to effector T cells. Since this equilibrium is frequently disrupted in individuals infected with the human immunodeficiency virus (HIV), we hypothesize that its deregulation could hamper immune reconstitution in patients with poor CD4(+) T cell recovery under highly active antiretroviral therapy (HAART). We analysed Tregs percentages amongst CD4(+) T cells in 53 HIV-infected patients under HAART, with suppression of viral replication and distinct levels of immune reconstitution. As controls, 51 healthy individuals were also analysed. We observed that amongst the patients with Nadir values (the lowest CD4(+) T cell counts achieved) <200 cells/µL, the individuals with high Tregs percentages (≥10% of total CD4(+) T cells) had the worse CD4(+) T cell reconstitution. In accordance, the well-described direct correlation between the Nadir value and CD4(+) T cell reconstitution is clearly more evident in individuals with high Tregs proportions. Furthermore, we observed a strong negative correlation between Tregs percentages and CD4(+) T cell recovery among immunological non-responder HIV(+) individuals. All together, this work shows that high Tregs frequency is an important factor associated with sub-optimal CD4(+) T cell recovery. This is particularly relevant for immunological non-responders with low Nadir values. Our results suggest that the Tregs proportion might be of clinical relevance to define cut-offs for HAART initiation.

Published
2013
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37. Virologic suppression in treatment-experienced patients after virologic rebound or failure of therapy.

Author

Sarmento-Castro R, Vasconcelos C, Aguas MJ, Marques R, and Oliveira J

Subjects
Clinical Trials as Topic, Drug Resistance, Viral, Humans, Medication Adherence, Treatment Outcome, Viral Load, Anti-HIV Agents administration & dosage, Antiretroviral Therapy, Highly Active methods, HIV Infections drug therapy, HIV Infections virology, Salvage Therapy methods
Abstract

Purpose of Review: To discuss factors related to virologic failure and review data from recent clinical trials evaluating re-suppression of viremia in extensively-treated HIV-infected patients with resistance., Recent Findings: Factors associated with virologic failure can be related to the virus (e.g. resistance), the patient (e.g. adherence) or HIV therapy (e.g. availability) and must be analyzed to minimize the likelihood of a new failure. Recent clinical trials have shown that it is now possible to achieve virologic suppression in a large proportion of treatment-experienced patients with extensive drug resistance, with several newer agents demonstrating favorable potency, tolerability and long-term efficacy., Summary: The benefits of highly active antiretroviral treatment are well recognized, and adding at least two (preferably three) new active drugs to an optimized background regimen can provide effective suppression of viremia even in multidrug-experienced patients. Changing drugs or regimen simplification should be considered when treatment is inadequate, poorly tolerated or associated with poor adherence, and is made easier by the newer agents and formulations now available. Newer antiretrovirals may contribute to a better quality of life and life expectancy in patients with few or no therapy options, although adherence is paramount in ensuring their continued effectiveness.

Published
2011
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38. Impact of peginterferon alpha-2b and ribavirin treatment on liver tissue in patients with HCV or HCV-HIV co-infection.

Author

Sarmento-Castro R, Horta A, Vasconcelos O, Coelho H, Mendez J, Tavares AP, Seabra J, Duarte M, Chaves L, Fortes O, Recalde C, Ventura A, Pires N, Pinho L, Dias N, and Carneiro F

Subjects
Adolescent, Adult, Antiretroviral Therapy, Highly Active, Antiviral Agents administration & dosage, Antiviral Agents adverse effects, Antiviral Agents pharmacology, Drug Therapy, Combination, Female, HIV Infections drug therapy, Hepatitis C complications, Humans, Interferon alpha-2, Interferon-alpha administration & dosage, Interferon-alpha adverse effects, Interferon-alpha pharmacology, Male, Middle Aged, Polyethylene Glycols, Recombinant Proteins, Ribavirin administration & dosage, Ribavirin adverse effects, Ribavirin pharmacology, Treatment Outcome, Antiviral Agents therapeutic use, HIV Infections complications, Hepatitis C drug therapy, Interferon-alpha therapeutic use, Liver drug effects, Ribavirin therapeutic use
Abstract

Objective: To evaluate the effect of treatment with peginterferon alpha-2b and ribavirin on liver histology in patients with chronic hepatitis C (CHC) with or without HIV infection., Methods: Patients received peginterferon alpha-2b (1.5 micro/kg/week during the first 4 weeks; 1.0 micro/kg/week thereafter) plus ribavirin (800-1200 mg/day, adjusted for weight) for 24 (genotypes 2/3) or 48 weeks (genotypes 1/4). Paired liver biopsy specimens were obtained at baseline and at the end of follow-up., Results: 108 paired biopsy specimens were available: 67 from HCV-monoinfected and 41 from co-infected patients. At the end of follow-up, necroinflammatory activity (NIA) was significantly reduced (P<0.001), and fibrosis scores improved by > or = 1 point (Ishak et al criteria) in 65.7% of HCV-monoinfected patients. In co-infected patients, NIA was significantly reduced (P<0.001), and fibrosis scores improved by > or = 1 point in 42.5% of cases. In both groups, results were better for patients who attained sustained virological response (SVR). HCV RNA was undetectable in the second biopsy specimens of all patients who attained SVR., Conclusion: Liver fibrosis is reduced significantly after a course of therapy in patients with chronic hepatitis C. Reduction of fibrosis is more significant in patients who are monoinfected with HCV and in those who attained SVR.

Published
2007
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