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1. Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries.

Author

Lodi, S, Del Amo, J, Moreno, S, Bucher, HC, Furrer, H, Logan, R, Sterne, J, Pérez-Hoyos, S, Jarrín, I, Phillips, A, Olson, A, Van Sighem, A, Reiss, P, Sabin, C, Jose, S, Justice, A, Goulet, J, Miró, JM, Ferrer, E, Meyer, L, Seng, R, Vourli, G, Antoniadou, A, Dabis, F, Vandenhede, MA, Costagliola, D, Abgrall, S, Hernán, MA, Hernan, M, Bansi, L, Hill, T, Dunn, D, Porter, K, Glabay, A, Orkin, C, Thomas, R, Jones, K, Fisher, M, Perry, N, Pullin, A, Churchill, D, Gazzard, B, Nelson, M, Asboe, D, Bulbeck, S, Mandalia, S, Clarke, J, Delpech, V, Anderson, J, Munshi, S, Post, F, Easterbrook, P, Khan, Y, Patel, P, Karim, F, Duffell, S, Gilson, R, Man, SL, Williams, I, Gompels, M, Dooley, D, Schwenk, A, Ainsworth, J, Johnson, M, Youle, M, Lampe, F, Smith, C, Grabowska, H, Chaloner, C, Ismajani Puradiredja, D, Walsh, J, Weber, J, Kemble, C, Mackie, N, Winston, A, Leen, C, Wilson, A, Bezemer, DO, Gras, LAJ, Kesselring, AM, Van Sighem, AI, Zaheri, S, Van Twillert, G, Kortmann, W, Branger, J, Prins, JM, Kuijpers, TW, Scherpbier, HJ, Van Der Meer, JTM, Wit, FWMN, Godfried, MH, Van Der Poll, T, Nellen, FJB, and Lange, JMA

Subjects
Humans, AIDS-Related Opportunistic Infections, HIV Infections, Neoplasms, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Incidence, Developed Countries, Adolescent, Adult, Aged, Middle Aged, United States, Europe, Female, Male, Young Adult, HIV, immune reconstitution inflammatory syndrome, incidence, inverse probability weighting, unmasking, Antiretroviral Therapy, Highly Active, HIV/AIDS, Infectious Diseases, Genetics, Behavioral and Social Science, Infection, Rare Diseases, Lymphoma, Cancer, Hematology, Tuberculosis, Virology, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences
Abstract

BackgroundThere is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis.MethodsWe identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, had CD4 cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4 cell count and HIV-RNA via inverse probability weighting.ResultsOut of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis.ConclusionWith the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries.

Published
2014

2. Development of a definition for rapid progression (RP) of renal function in HIV-positive persons:the D:A:D study

Author

Kamara, David A., Ryom, Lene, Ross, Michael, Kirk, Ole, Reiss, Peter, Morlat, Philippe, Moranne, Olivier, Fux, Christoph A., Mocroft, Amanda, Sabin, Caroline, Lundgren, Jens D., Smith, Colette J, D:A:D study, Group., Quiros, Roldan, Powderly B, M. E., Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Ryom, L, Sabin, Ca, Kamara, D, Smith, C, Phillips, A, Mocroft, A, Tverland, J, Mansfeld, M, Nielsen, J, Raben, D, Lundgren, Jd, Brandt, R, Rickenbach, M, Fanti, I, Krum, E, Hillebregt, M, Geffard, S, Sundström, A, Delforge, M, Fontas, E, Torres, F, Mcmanus, H, Wright, S, Kjær, J, Sjøl, A, Meidahl, P, Helweg-Larsen, J, Iversen, J, Kirk, O, Reiss, P, Ross, M, Fux, Ca, Morlat, P, Moranne, O, Kesselring, Am, Kamara, Da, Weber, R, Pradier, C, Friis-Møller, N, Kowalska, J, Sabin, C, Law, M, d'Arminio Monforte, A, Dabis, F, Bruyand, M, Bower, M, Fätkenheuer, G, Donald, A, Grulich, A, Zaheri, S, Gras, L, Prins, Jm, Kuijpers, Tw, Scherpbier, Hj, van der Meer JT, Wit, Fw, Godfried, Mh, van der Poll, D, Nellen, Fj, Lange, Jm, Geerlings, Se, van Vugt, M, Pajkrt, D, Bos, D, van der Valk, D, Grijsen, Ml, Wiersinga, Wj, Goorhuis, A, Hovius, Jw, Lowe, S, Lashof, A, Posthouwer, D, Ammerlaan, Hs, Pronk, Mj, van der Ende ME, de Vries-Sluijs TE, Schurink, Ca, Nouwen, Jl, Verbon, A, Rijnders, Bj, van Gorp EC, van der Feltz, M, Driessen, Gj, van Rossum AM, Branger, J, Schippers, F, van Nieuwkoop, C, van Elzakker EP, Groeneveld, Ph, Bouwhuis, Jw, Soetekouw, R, ten Kate RW, Kroon, Fp, van Dissel JT, Arend, Sm, de Boer MG, Jolink, H, ter Vollaard HJ, Bauer, Mp, den Hollander JG, Pogany, K, van Twillert, D, Kortmann, W, Stuart, Jw, Diederen, Bm, Leyten, Ms, Gelinck, Lb, Kootstra, Gj, Delsing, Ce, Brinkman, K, Blok, Wl, Frissen, Ph, Schouten, We, van den Berk GE, van Kasteren ME, Brouwer, Ae, Veenstra, J, Lettinga, Kd, Mulder, Jw, Vrouenraets, Sm, Lauw, Fn, van Eeden, A, Verhagen, Dw, Sprenger, Hg, Doedens, R, Scholvinck, Eh, van Assen, S, Bierman, Wf, Koopmans, Pp, Keuter, M, van der Ven AJ, ter Hofstede HJ, Dofferhoff, As, Warris, A, van Crevel, R, Hoepelman, Ai, Mudrikova, T, Schneider, Mm, Ellerbroek, Pm, Oosterheert, Jj, Arends, Je, Wassenberg, Mw, Barth, Re, van Agtmael, M, Perenboom, Rm, Claessen, Fa, Bomers, M, Peters, Ej, Geelen, Sp, Wolfs, Tf, Bont, Lj, Richter, C, van der Berg JP, Gisolf, Eh, van den Berge, M, Stegeman, A, van Vonderen MG, van Houte DP, Weijer, S, el Moussaoui, R, Winkel, C, Muskiet, F, Durand, Voigt, R, Chêne, G, Lawson-Ayayi, S, Thiébaut, R, Bonnal, F, Bonnet, F, Bernard, N, Caunègre, L, Cazanave, C, Ceccaldi, J, Chambon, D, Chossat, I, Dauchy, Fa, De Witte, S, Dupon, M, Duffau, P, Dutronc, H, Farbos, S, Gaborieau, V, Gemain, Mc, Gerard, Y, Greib, C, Hessamfar, M, Lacoste, D, Lataste, P, Lafarie, S, Lazaro, E, Malvy, D, Meraud, Jp, Mercié, P, Monlun, E, Neau, D, Ochoa, A, Pellegrin, Jl, Pistone, T, Ragnaud, Jm, Receveur, Mc, Tchamgoué, S, Vandenhende, Ma, Viallard, Jf, Moreau, Jf, Pellegrin, I, Fleury, H, Lafon, Me, Masquelier, B, Trimoulet, P, Breilh, D, Haramburu, F, Miremont-Salamé, G, Blaizeau, Mj, Decoin, M, Delaune, J, Delveaux, S, D'Ivernois, C, Hanapier, C, Leleux, O, Uwamaliya-Nziyumvira, B, Sicard, X, Palmer, G, Touchard, D, Petoumenos, K, Bendall, C, Moore, R, Edwards, S, Hoy, J, Watson, K, Roth, N, Nicholson, J, Bloch, M, Franic, T, Baker, D, Vale, R, Carr, A, Cooper, D, Chuah, J, Ngieng, M, Nolan, D, Skett, J, Calvo, G, Mateu, S, Domingo, P, Sambeat, Ma, Gatell, J, Del Cacho, E, Cadafalch, J, Fuster, M, Codina, C, Sirera, G, Vaqué, A, De Wit, S, Clumeck, N, Necsoi, C, Gennotte, Af, Gerard, M, Kabeya, K, Konopnicki, D, Libois, A, Martin, C, Payen, Mc, Semaille, P, Van Laethem, Y, Neaton, J, Bartsch, G, El-Sadr, Wm, Thompson, G, Wentworth, D, Luskin-Hawk, R, Telzak, E, Abrams, Di, Cohn, D, Markowitz, N, Arduino, R, Mushatt, D, Friedland, G, Perez, G, Tedaldi, E, Fisher, E, Gordin, F, Crane, Lr, Sampson, J, Baxter, J, Lundgren, J, Cozzi-Lepri, A, Grint, D, Podlekareva, D, Peters, L, Reekie, J, Fischer, Ah, Losso, M, Elias, C, Vetter, N, Zangerle, R, Karpov, I, Vassilenko, A, Mitsura, Vm, Suetnov, O, Colebunders, R, Vandekerckhove, L, Hadziosmanovic, V, Kostov, K, Machala, L, Begovac, J, Jilich, D, Sedlacek, D, Kronborg, G, Gerstoft, J, Benfield, T, Larsen, M, Katzenstein, T, Hansen, Ab, Skinhøj, P, Pedersen, C, Ostergaard, L, Zilmer, K, Smidt, J, Ristola, M, Katlama, C, Viard, J, Girard, P, Livrozet, Jm, Vanhems, P, Rockstroh, J, Schmidt, R, van Lunzen, J, Degen, O, Stellbrink, Hj, Staszewski, S, Bickel, M, Kosmidis, J, Gargalianos, P, Xylomenos, G, Perdios, J, Panos, G, Filandras, A, Karabatsaki, E, Sambatakou, H, Banhegyi, D, Mulcahy, F, Yust, I, Turner, D, Burke, M, Pollack, S, Hassoun, G, Maayan, S, Vella, S, Esposito, R, Mazeu, I, Mussini, C, Arici, C, Pristera, R, Mazzotta, F, Gabbuti, A, Vullo, V, Lichtner, M, Chirianni, A, Montesarchio, E, Gargiulo, M, Antonucci, G, Testa, A, Narciso, P, Vlassi, C, Zaccarelli, M, Lazzarin, A, Castagna, A, Gianotti, N, Galli, M, Ridolfo, A, Rozentale, B, Zeltina, I, Chaplinskas, S, Hemmer, R, Staub, T, Ormaasen, V, Maeland, A, Bruun, J, Knysz, B, Gasiorowski, J, Horban, A, Bakowska, E, Grzeszczuk, A, Flisiak, R, Boron-Kaczmarska, A, Pynka, M, Parczewski, M, Beniowski, M, Mularska, E, Trocha, H, Jablonowska, E, Malolepsza, E, Wojcik, K, Antunes, F, Doroana, M, Caldeira, L, Mansinho, K, Maltez, F, Duiculescu, D, Rakhmanova, A, Babes, V, Zakharova, N, Jevtovic, D, Mokráš, M, Staneková, D, Tomazic, J, González-Lahoz, J, Soriano, V, Labarga, P, Medrano, J, Moreno, S, Rodriguez, Jm, Clotet, B, Jou, A, Paredes, R, Tural, C, Puig, J, Bravo, I, Gatell, Jm, Miró, Jm, Gutierrez, M, Karlsson, A, Mateo, G, Flamholc, L, Ledergerber, B, Francioli, P, Cavassini, M, Hirschel, B, Boffi, E, Kravchenko, E, Furrer, H, Battegay, M, Elzi, L, Chentsova, N, Frolov, V, Kutsyna, G, Servitskiy, S, Krasnov, M, Barton, S, Johnson, Am, Mercey, D, Johnson, Ma, Murphy, M, Weber, J, Scullard, G, Fisher, M, Leen, C, Morfeldt, L, Thulin, G, Åkerlund, B, Koppel, K, Håkangård, C, Moroni, M, Angarano, G, Antinori, A, Armignacco, O, Castelli, F, Cauda, R, Di Perri, G, Iardino, R, Ippolito, G, Perno, Cf, von Schloesser, F, Viale, P, Ceccherini-Silberstein, F, Girardi, E, Lo Caputo, S, Puoti, M, Andreoni, M, Ammassari, A, Balotta, C, Bonfanti, P, Bonora, S, Borderi, M, Capobianchi, Mr, Cingolani, A, Cinque, P, De Luca, A, Di Biagio, A, Gori, A, Guaraldi, G, Lapadula, G, Madeddu, G, Maggiolo, F, Marchetti, G, Marcotullio, S, Monno, L, Quiros, E, Rusconi, S, Cicconi, P, Formenti, T, Galli, L, Lorenzini, P, Giacometti, A, Costantini, A, Santoro, C, Suardi, C, Vanino, E, Verucchi, G, Quiros Roldan, E, Minardi, C, Quirino, T, Abeli, C, Manconi, Pe, Piano, P, Vecchiet, J, Falasca, K, Sighinolfi, L, Segala, D, Cassola, G, Viscoli, G, Alessandrini, A, Piscopo, R, Mazzarello, G, Mastroianni, C, Belvisi, V, Caramma, I, Castelli, Ap, Rizzardini, G, Ridolfo, Al, Piolini, R, Salpietro, S, Carenzi, L, Moioli, Mc, Puzzolante, C, Onofrio, M, Abrescia, N, Guida, Mg, Baldelli, F, Francisci, D, Parruti, G, Ursini, T, Magnani, G, Ursitti, Ma, d' Avino, A, Gallo, L, Nicastri, E, Acinapura, R, Capozzi, M, Libertone, R, Tebano, G, Cattelan, A, Mura, Ms, Caramello, P, Orofino, Gc, Sciandra, M, Pellizzer, G, Manfrin, V, Caissotti, C, Dellamonica, P, Bernard, E, Cua, E, De Salvador- Guillouet, F, Durant, J, Ferrando, S, Mondain-Miton, V, Naqvi, A, Perbost, I, Prouvost-Keller, B, Pillet, S, Pugliese, P, Rahelinirina, V, Roger, Pm, Dollet, K, Aubert, V, Barth, J, Bernasconi, E, Böni, J, Bucher, Hc, Burton- Jeangros, C, Calmy, A, Egger, M, Fehr, J, Fellay, J, Gorgievski, M, Günthard, H, Haerry, D, Hasse, B, Hirsch, Hh, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kovari, H, Martinetti, G, de Tejada BM, Metzner, K, Müller, N, Nadal, D, Pantaleo, G, Rauch, A, Regenass, A, Rudin, C, Schmid, P, Schultze, D, Schöni-Affolter, F, Schüpbach, J, Speck, R, Taffé, P, Tarr, P, Telenti, A, Trkola, A, Vernazza, P, Yerly, S., AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Other departments, Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, General Internal Medicine, Dermatology, Medical Microbiology and Infection Prevention, Sea to Shore Alliance, University of Florida [Gainesville] (UF), Observatoire des Micro et Nano Technologies (OMNT - UMS 2920), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Structures et propriétés d'architectures moléculaire (SPRAM - UMR 5819), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Département de santé publique, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital Larchet, Service de néphrologie, Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Department of primary care and population sciences, University College of London [London] (UCL), Research Department of Infection and Population Health [London], Economics, Umeå University, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut Nanosciences et Cryogénie (INAC), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
Adult, Male, CHRONIC KIDNEY-DISEASE, Internationality, FUNCTION DECLINE, diagnosis, nephrology, Chronic kidney disease, Estimated glomerular filtration rate, HIV, Kidney disease, Rapid progression, D:A:D study Group, HIV Infections, urologic and male genital diseases, Sensitivity and Specificity, Severity of Illness Index, GLOMERULAR-FILTRATION-RATE, renal insufficiency, NO, MORTALITY RISK, ANTIRETROVIRAL THERAPY, 80 and over, Humans, chronic kidney disease, estimated glomerular filtration rate, hiv, kidney disease, rapid progression, adult, aged, aged, 80 and over, diagnosis, computer-assisted, disease progression, female, glomerular filtration rate, hiv infections, humans, internationality, male, middle aged, renal insufficiency, chronic, reproducibility of results, sensitivity and specificity, algorithms, severity of illness index, Diagnosis, Computer-Assisted, Renal Insufficiency, Chronic, ComputingMilieux_MISCELLANEOUS, BODY-SURFACE AREA, POPULATION, Aged, Aged, 80 and over, INFECTED PATIENTS, Reproducibility of Results, 1103 Clinical Sciences, ASSOCIATION, Urology & Nephrology, Middle Aged, chronic, INDIVIDUALS, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, computer-assisted, Disease Progression, Female, Algorithms, Research Article, Glomerular Filtration Rate
Abstract

BACKGROUND: No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011. METHODS: Two definitions were evaluated; RP definition A: An average eGFR decline (slope) ≥5 ml/min/1.73 m2/year over four years of follow-up with ≥3 eGFR measurements/year, last eGFR

Published
2014

3. Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Author

Mocroft, A, Lundgren, JD, Ross, M, Law, M, Reiss, P, Kirk, O, Smith, C, Wentworth, D, Neuhaus, J, Fux, CA, Moranne, O, Morlat, P, Johnson, MA, Ryom, L, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Sabin, CA, Phillips, A, Weber, R, Pradier, C, d'Arminio Monforte, A, Dabis, F, El-Sadr, WM, De Wit, S, Kamara, D, Tverland, J, Mansfeld, M, Nielsen, J, Raben, D, Salbøl Brandt, R, Rickenbach, M, Fanti, I, Krum, E, Hillebregt, M, Geffard, S, Sundström, A, Delforge, M, Fontas, E, Torres, F, McManus, H, Wright, S, Kjær, J, Sjøl, A, Meidahl, P, Helweg-Larsen, J, Schmidt Iversen, J, Kesselring, AM, Friis-Møller, N, Kowalska, J, Sabin, C, Bruyand, M, Bower, M, Fätkenheuer, G, Donald, A, Grulich, A, Prins, JM, Kuijpers, TW, Scherpbier, HJ, van der Meer, JTM, Wit, FWMN, Godfried, MH, van der Poll, T, Nellen, FJB, Geerlings, SE, van Vugt, M, Pajkrt, D, Bos, JC, Wiersinga, WJ, van der Valk, M, Goorhuis, A, Hovius, JW, van Eden, J, Henderiks, A, van Hes, AMH, Mutschelknauss, M, Nobel, HE, Pijnappel, FJJ, Westerman, AM, Jurriaans, S, Back, NKT, Zaaijer, HL, Berkhout, B, Cornelissen, MTE, Schinkel, CJ, Thomas, XV, van den Berge, M, Stegeman, A, Baas, S, Hage de Looff, L, Versteeg, D, Pronk, MJH, Ammerlaan, HSM, Korsten-Vorstermans, EMHM, de Munnik, ES, Jansz, AR, Tjhie, J, Mocroft, A, Lundgren, JD, Ross, M, Law, M, Reiss, P, Kirk, O, Smith, C, Wentworth, D, Neuhaus, J, Fux, CA, Moranne, O, Morlat, P, Johnson, MA, Ryom, L, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Sabin, CA, Phillips, A, Weber, R, Pradier, C, d'Arminio Monforte, A, Dabis, F, El-Sadr, WM, De Wit, S, Kamara, D, Tverland, J, Mansfeld, M, Nielsen, J, Raben, D, Salbøl Brandt, R, Rickenbach, M, Fanti, I, Krum, E, Hillebregt, M, Geffard, S, Sundström, A, Delforge, M, Fontas, E, Torres, F, McManus, H, Wright, S, Kjær, J, Sjøl, A, Meidahl, P, Helweg-Larsen, J, Schmidt Iversen, J, Kesselring, AM, Friis-Møller, N, Kowalska, J, Sabin, C, Bruyand, M, Bower, M, Fätkenheuer, G, Donald, A, Grulich, A, Prins, JM, Kuijpers, TW, Scherpbier, HJ, van der Meer, JTM, Wit, FWMN, Godfried, MH, van der Poll, T, Nellen, FJB, Geerlings, SE, van Vugt, M, Pajkrt, D, Bos, JC, Wiersinga, WJ, van der Valk, M, Goorhuis, A, Hovius, JW, van Eden, J, Henderiks, A, van Hes, AMH, Mutschelknauss, M, Nobel, HE, Pijnappel, FJJ, Westerman, AM, Jurriaans, S, Back, NKT, Zaaijer, HL, Berkhout, B, Cornelissen, MTE, Schinkel, CJ, Thomas, XV, van den Berge, M, Stegeman, A, Baas, S, Hage de Looff, L, Versteeg, D, Pronk, MJH, Ammerlaan, HSM, Korsten-Vorstermans, EMHM, de Munnik, ES, Jansz, AR, and Tjhie, J

Abstract

Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7–6.7; median follow-up 6.1 y, range 0.3–9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was −2 (interquartile range –4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0–4, 103 events) and high risk groups (risk score ≥ 5, 505 events), respectiv

Published
2015

4. Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D Study

Author

Mocroft, Amanda, Lundgren, Jens D, Ross, Michael, Law, Matthew, Reiss, Peter, Kirk, Ole, Smith, Colette, Wentworth, Deborah, Neuhaus, Jacqueline, Fux, Christoph A, Moranne, Olivier, Morlat, Phillipe, Johnson, Margaret A, Ryom, Lene, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Sabin, CA, Phillips, A, Weber, R, Pradier, C, d'Arminio Monforte, A, Dabis, F, El-Sadr, WM, De Wit, S, Kamara, D, Tverland, J, Mansfeld, M, Nielsen, J, Raben, D, Salbøl Brandt, R, Rickenbach, M, Fanti, I, Krum, E, Hillebregt, M, Geffard, S, Sundström, A, Delforge, M, Fontas, E, Torres, F, McManus, H, Wright, S, Kjær, J, Sjøl, A, Meidahl, P, Helweg-Larsen, J, Schmidt Iversen, J, Kesselring, AM, Friis-Møller, N, Kowalska, J, Sabin, C, Bruyand, M, Kamara, DA, Bower, M, Fätkenheuer, G, Donald, A, Grulich, A, Prins, JM, Kuijpers, TW, Scherpbier, HJ, van der Meer, JTM, Wit, FWMN, Godfried, MH, van der Poll, T, Nellen, FJB, Geerlings, SE, van Vugt, M, Pajkrt, D, Bos, JC, Wiersinga, WJ, van der Valk, M, Goorhuis, A, Hovius, JW, van Eden, J, Henderiks, A, van Hes, AMH, Mutschelknauss, M, Nobel, HE, Pijnappel, FJJ, Westerman, AM, Jurriaans, S, Back, NKT, Zaaijer, HL, Berkhout, B, Cornelissen, MTE, Schinkel, CJ, Thomas, XV, van den Berge, M, Stegeman, A, Baas, S, Hage de Looff, L, Versteeg, D, Pronk, MJH, Ammerlaan, HSM, Korsten-Vorstermans, EMHM, de Munnik, ES, Jansz, AR, Tjhie, J, Rogers, Gary, Mocroft, Amanda, Lundgren, Jens D, Ross, Michael, Law, Matthew, Reiss, Peter, Kirk, Ole, Smith, Colette, Wentworth, Deborah, Neuhaus, Jacqueline, Fux, Christoph A, Moranne, Olivier, Morlat, Phillipe, Johnson, Margaret A, Ryom, Lene, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Sabin, CA, Phillips, A, Weber, R, Pradier, C, d'Arminio Monforte, A, Dabis, F, El-Sadr, WM, De Wit, S, Kamara, D, Tverland, J, Mansfeld, M, Nielsen, J, Raben, D, Salbøl Brandt, R, Rickenbach, M, Fanti, I, Krum, E, Hillebregt, M, Geffard, S, Sundström, A, Delforge, M, Fontas, E, Torres, F, McManus, H, Wright, S, Kjær, J, Sjøl, A, Meidahl, P, Helweg-Larsen, J, Schmidt Iversen, J, Kesselring, AM, Friis-Møller, N, Kowalska, J, Sabin, C, Bruyand, M, Kamara, DA, Bower, M, Fätkenheuer, G, Donald, A, Grulich, A, Prins, JM, Kuijpers, TW, Scherpbier, HJ, van der Meer, JTM, Wit, FWMN, Godfried, MH, van der Poll, T, Nellen, FJB, Geerlings, SE, van Vugt, M, Pajkrt, D, Bos, JC, Wiersinga, WJ, van der Valk, M, Goorhuis, A, Hovius, JW, van Eden, J, Henderiks, A, van Hes, AMH, Mutschelknauss, M, Nobel, HE, Pijnappel, FJJ, Westerman, AM, Jurriaans, S, Back, NKT, Zaaijer, HL, Berkhout, B, Cornelissen, MTE, Schinkel, CJ, Thomas, XV, van den Berge, M, Stegeman, A, Baas, S, Hage de Looff, L, Versteeg, D, Pronk, MJH, Ammerlaan, HSM, Korsten-Vorstermans, EMHM, de Munnik, ES, Jansz, AR, Tjhie, J, and Rogers, Gary

Published
2015

5. Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per microL in Europe and North America: a pooled cohort observational study

Author

Study Group on Death Rates at High CD4 Count in Antiretroviral Naive Patients, Lodwick, Rk, Sabin, Ca, Porter, K, Ledergerber, B, van Sighem, A, Cozzi Lepri, A, Khaykin, P, Mocroft, A, Jacobson, L, De Wit, S, Obel, N, Castagna, A, Wasmuth, Jc, Gill, J, Klein, Mb, Gange, S, Riera, M, Mussini, C, Gutiérrez, F, Touloumi, G, Carrieri, P, Guest, Jl, Brockmeyer, Nh, Collaborators: Antoniadou A, Phillips A. N., Gargalianos Kakolyris, P, Katsarou, O, Kordossis, T, Lazanas, M, Panos, G, Paparizos, V, Paraskevis, D, Petrikkos, G, Sambatakou, H, Skoutelis, A, Pantazis, N, Bakoyannis, G, Gioukari, V, de Wolf, F, Bezemer, Do, Gras, La, Kesselring, Am, van Sighem AI, Smit, C, Zhang, S, Zaheri, S, Prins, Jm, Schreij, G, Bravenboer, B, van der Ende ME, Kauffmann, Rh, ten Kate RW, Kroon, Fp, Bronsveld, W, Vriesendorp, R, van Houte, D, ten Napel CH, Brinkman, K, van Eeden, A, Mulder, Jw, Juttmann, Jr, Veenstra, J, Koopmans, Pp, Sprenger, Hg, Hoepelman, Im, Danner, Sa, Richter, C, Tanis, Aa, Clumeck, N, Delforge, M, Necsoi, C, Demeester, R, Gennotte, Af, Gerard, M, Guillaume, Mp, Hermans, P, Kabeya, K, Konopnicki, D, Martin, C, Libois, A, Payen, Mc, Semaille, P, Van Laethem, Y, Del Amo, J, Meyer, L, Bucher, Hc, Chêne, G, Pillay, D, Prins, M, Rosinska, M, Sabin, C, Lodi, S, Coughlin, K, Walker, S, Babiker, A, Bucher, H, de Luca, A, Fisher, M, Muga, R, Fätkenheuer, G, Rockstroh, J, Vehreschild, J, Hertenstein, C, Berenguer, J, del Amo, J, García, F, Labarga, P, Moreno, S, Angeles Muñoz, M, Caro Murillo AM, Sobrino, P, Pérez Cachafeiro, S, Jarrín, I, Alejos, B, García, I, Gómez Sirvent, J, Soriano, V, Pulido, F, Iribarren, J, Masiá, M, Vidal, F, Sanz, J, Blanco, Ja, Sola, J, Gerstoft, J, Kronborg, G, Røge, B, Larsen, Cs, Pedersen, G, Laursen, Al, Nielsen, L, Jensen, J, Babacan, E, Bickel, M, Bodtländer, A, Brodt, Hr, Carlebach, A, Gute, P, Haberl, A, Helm, E, Klauke, S, Knecht, G, Lennemann, T, Locher, L, Lutz, T, Mösch, M, Müller, A, Nisius, G, Staszewski, S, Stephan, C, Stürmer, M, von Hentig, N, Wolf, T, Rimland, D, Moanna, A, Moorfield, M, Dorsey, M, Desilva, Ke, Schlueter Wirtz, S, Mindley, R, Dozier, R, Robinson, Y, Brown, P, Moroni, M, Angarano, G, Antinori, A, Carosi, G, Cauda, R, d'Arminio Monforte, A, Di Perri, G, Galli, M, Ghinelli, G, Iardino, R, Ippolito, G, Lazzarin, A, Mazzotta, F, Perno, Cf, Viale, Pl, Von Schlosser, F, Ammassari, A, Balotta, C, Bonfanti, P, Capobianchi, Mr, Ceccherini Silberstein, F, De Luca, A, Gervasoni, C, Girardi, E, Lo Caputo, S, Maggiolo, F, Murri, R, Puoti, M, Torti, Carlo, Salpietro, S, Marangione, M, Galli, L, Gianotti, N, Cossarini, F, Spagnuolo, V, Arendt, G, Esser, S, Jäger, H, Schwarze, S, Stoll, M, Wolf, H, Jansen, K, Michalik, C, Skaletz Rorowski, A, Königs, C, Gingelmaier, A, Margolick, Jb, Jacobson, Lp, Phair, Jp, Wolinsky, Sm, Detels, R, Rinaldo, Cr, Boirot, C, Bouhnik, Ad, Carrieri, Mp, Cassuto, Jp, Chesney, M, Cohen, J, Dellamonica, P, Dujardin, P, Gallais, H, Gastaut, Ja, Kurkdji, P, Lepeu, G, Mechali, D, Moatti, Jp, Moreau, J, Nègre, M, Obadia, Y, Poizot Martin, I, Pradier, C, Préau, M, Rey, D, Roux, P, Rouzioux, C, Sobel, A, Spire, B, Trémolières, F, Villes, V, Vincent, E, Vlahov, D, Borghi, V, Casabona, J, Miró, Jm, Gatell, Jm, López Dieguez Puerta, M, Tural, C, Clotet, B, Podzamczer, D, Ferrer, E, Murillas, J, Segura, F, Navarro, G, Force, L, Vilaró, J, Masabeu, A, Guadarrama, M, Betancourt, Aj, Romero, A, Agustí, C, Battegay, M, Bernasconi, E, Böni, J, Bürgisser, P, Calmy, A, Cavassini, M, Dubs, R, Egger, M, Elzi, L, Fischer, M, Flepp, M, Fontana, A, Francioli, P, Furrer, H, Fux, Ca, Gorgievski, M, Günthard, Hf, Hirsch, Hh, Hirschel, B, Hösli, I, Kahlert, C, Kaiser, L, Karrer, U, Kind, C, Klimkait, T, Martinetti, G, Martinez, B, Müller, N, Nadal, D, Paccaud, F, Pantaleo, G, Rauch, A, Regenass, S, Rickenbach, M, Rudin, C, Schmid, P, Schultze, D, Schöni, F, Schüpbach, J, Speck, R, Taffé, P, Telenti, A, Trkola, A, Vernazza, P, Weber, R, Yerly, S, Ainsworth, J, Anderson, J, Delpech, V, Dunn, D, Easterbrook, P, Gazzard, B, Gilson, R, Gompels, M, Hill, T, Johnson, M, Leen, C, Nelson, M, Orkin, C, Palfreeman, A, Phillips, A, Post, F, Schwenk, A, Walsh, J, Bansi, L, Huntington, S, Glabay, A, Anastos, K, Minkoff, H, Young, M, Greenblatt, R, Levine, A, Cohen, M, and Gange, S.

Published
2010

6. Immune restoration and onset of new AIDS-defining events with combination antiretroviral therapy in HIV type-1-infected immigrants in the Netherlands.

Author

Kesselring AM, Gras L, Wit FW, Smit C, Geerlings SE, Mulder JW, Schreij G, Sprenger HG, Reiss P, and de Wolf F

Subjects
Acquired Immunodeficiency Syndrome drug therapy, Acquired Immunodeficiency Syndrome immunology, Adult, CD4 Lymphocyte Count, Cohort Studies, Emigrants and Immigrants, Female, HIV Infections ethnology, HIV Infections transmission, Humans, Male, Middle Aged, Netherlands ethnology, Acquired Immunodeficiency Syndrome classification, Acquired Immunodeficiency Syndrome ethnology, Antiretroviral Therapy, Highly Active, HIV Infections immunology, HIV-1 immunology
Abstract

Background: We investigated differences in immune restoration and onset of new AIDS-defining events on combination antiretroviral therapy (cART) among HIV type-1 (HIV-1)-infected patients of different regional origin now living in the Netherlands., Methods: Treatment-naive adults reaching plasma viral load (pVL)<400 copies/ml within 9 months of starting cART were selected from the Netherlands ATHENA cohort. CD4(+) T-cell response on cART was determined over 7 years using mixed models. CD4(+) T-cell counts were excluded from the analyses at the first of two consecutive measurements of pVL≥400 copies/ml following prior suppression to <400 copies/ml. Multivariate analyses included gender, age, CD4(+) T-cell count and pVL prior to cART, hepatitis coinfection, HIV-1 transmission and region of origin (Western Europe/North America [WN], sub-Saharan Africa [SSA], Southeast Asia [SEA], Latin America/Caribbean [LAC] or other)., Results: For 6,057 selected patients (WN 3,947, SSA 989, SEA 237, LAC 695 and other 189), median follow-up was 3.2 years (WN 3.3, SSA 2.9, SEA 3.2, LAC 2.7 and other 2.7). CD4(+) T-cell increase in the first 6 months of cART was lower in males than females (-26 cells/mm(3); P<0.0001) and in patients from SSA compared with WN (-36 cells/mm(3); P<0.0001). Because men from SSA started with lower CD4(+) T-cell counts than men from WN, they continued to lag behind and had lower absolute CD4(+) T-cell counts after 7 years of cART. Furthermore, cumulative tuberculosis incidence after 7 years of cART was higher in SSA compared with WN (4.5% versus 0.5%, hazard ratio 5.08, 95% confidence interval 2.22-11.60)., Conclusions: HIV-1-infected immigrants from SSA have blunted immune restoration on fully suppressive cART and should be identified at an earlier disease stage. Our results call for more intensive screening for both latent and active tuberculosis in these patients.

Published
2010
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7. Risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy.

Author

Kesselring AM, Wit FW, Sabin CA, Lundgren JD, Gill MJ, Gatell JM, Rauch A, Montaner JS, de Wolf F, Reiss P, and Mocroft A

Subjects
Adult, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active adverse effects, Antiretroviral Therapy, Highly Active methods, CD4 Lymphocyte Count, Drug Hypersensitivity etiology, Female, HIV Infections immunology, HIV Infections mortality, Humans, Male, Middle Aged, Nevirapine therapeutic use, Retrospective Studies, Risk Factors, Treatment Outcome, Viral Load, Anti-HIV Agents adverse effects, HIV Infections drug therapy, Nevirapine adverse effects
Abstract

Background: This collaboration of seven observational clinical cohorts investigated risk factors for treatment-limiting toxicities in both antiretroviral-naive and experienced patients starting nevirapine-based combination antiretroviral therapy (NVPc)., Methods: Patients starting NVPc after 1 January 1998 were included. CD4 cell count at starting NVPc was classified as high (>400/microl/>250/microl for men/women, respectively) or low. Cox models were used to investigate risk factors for discontinuations due to hypersensitivity reactions (HSR, n = 6547) and discontinuation of NVPc due to treatment-limiting toxicities and/or patient/physician choice (TOXPC, n = 10,186). Patients were classified according to prior antiretroviral treatment experience and CD4 cell count/viral load at start NVPc. Models were stratified by cohort and adjusted for age, sex, nadir CD4 cell count, calendar year of starting NVPc and mode of transmission., Results: Median time from starting NVPc to TOXPC and HSR were 162 days [interquartile range (IQR) 31-737] and 30 days (IQR 17-60), respectively. In adjusted Cox analyses, compared to naive patients with a low CD4 cell count, treatment-experienced patients with high CD4 cell count and viral load more than 400 had a significantly increased risk for HSR [hazard ratio 1.45, confidence interval (CI) 1.03-2.03] and TOXPC within 18 weeks (hazard ratio 1.34, CI 1.08-1.67). In contrast, treatment-experienced patients with high CD4 cell count and viral load less than 400 had no increased risk for HSR 1.10 (0.82-1.46) or TOXPC within 18 weeks (hazard ratio 0.94, CI 0.78-1.13)., Conclusion: Our results suggest it may be relatively well tolerated to initiate NVPc in antiretroviral-experienced patients with high CD4 cell counts provided there is no detectable viremia.

Published
2009
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8. Discontinuation of nevirapine because of hypersensitivity reactions in patients with prior treatment experience, compared with treatment-naive patients: the ATHENA cohort study.

Author

Wit FW, Kesselring AM, Gras L, Richter C, van der Ende ME, Brinkman K, Lange JM, de Wolf F, and Reiss P

Subjects
Adult, CD4 Lymphocyte Count, Chemical and Drug Induced Liver Injury, Cohort Studies, Drug Administration Schedule, Drug Therapy, Combination, Exanthema chemically induced, Female, HIV Infections virology, HIV-1, Humans, Male, Multivariate Analysis, Netherlands, Treatment Outcome, Anti-HIV Agents administration & dosage, Anti-HIV Agents adverse effects, Anti-HIV Agents therapeutic use, Drug Hypersensitivity etiology, HIV Infections drug therapy, Nevirapine administration & dosage, Nevirapine adverse effects, Nevirapine therapeutic use, Reverse Transcriptase Inhibitors administration & dosage, Reverse Transcriptase Inhibitors adverse effects, Reverse Transcriptase Inhibitors therapeutic use
Abstract

Background: Recommendations that nevirapine (NVP) should be avoided in female individuals with CD4 cell counts >250 cells/microL and in male individuals with CD4 cell counts >400 cells/microL are based on findings in treatment-naive patients. It is unclear whether these guidelines also apply to treatment-experienced patients switching to NVP-based combination therapy., Methods: Patients in the ATHENA cohort study who had used NVP-based combination therapy were included. We identified patients who discontinued NVP-based combination therapy because of hypersensitivity reactions (HSRs; rash and/or hepatotoxicity) within 18 weeks after starting such therapy. We grouped patients according to their CD4 cell count at the start of NVP-based combination therapy (current CD4 cell count) as having a high CD4 cell count (for female patients, >250 cells/microL; for male patients, >400 cells/microL) or a low CD4 cell count. Treatment-experienced patients were further subdivided according to the last available CD4 cell count before first receipt of antiretroviral therapy (ART; pre-ART CD4 cell count) using the same criteria. Risk factors for HSR were assessed using multivariate logistic regression., Results: Of 3752 patients receiving NVP-based combination therapy, 231 patients (6.2%) discontinued NVP therapy because of HSRs. Independent risk factors included female sex and Asian ethnicity. Having an undetectable viral load (VL) at the start of NVP therapy was associated with reduced risk of developing an HSR (adjusted odds ratio [OR], 0.52; 95% confidence interval [CI], 0.38-0.71). Pretreated patients with low pre-ART and high current CD4 cell counts and a detectable VL when switching to NVP-based combination therapy had a significantly higher risk of developing an HSR, compared with treatment-naive patients who started NVP therapy with low CD4 cell counts (adjusted OR, 1.87; 95% CI, 1.11-3.12); pretreated patients with low pre-ART CD4 cell counts who switched to NVP therapy with a high current CD4 cell count and an undetectable VL did not have an increased risk of developing an HSR (adjusted OR, 1.03; 95% CI, 0.66-1.61)., Conclusions: Treatment-experienced patients who start NVP-based combination therapy with low pre-ART and high current CD4 cell counts and an undetectable VL have a similar likelihood for discontinuing NVP therapy because of HSRs, compared with treatment-naive patients with low CD4 cell counts. This suggests that NVP-based combination therapy may be safely initiated in such patients. However, in similar patients with a detectable VL, it is prudent to continue to adhere to current CD4 cell count thresholds.

Published
2008
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9. CD4 cell counts of 800 cells/mm3 or greater after 7 years of highly active antiretroviral therapy are feasible in most patients starting with 350 cells/mm3 or greater.

Author

Gras L, Kesselring AM, Griffin JT, van Sighem AI, Fraser C, Ghani AC, Miedema F, Reiss P, Lange JM, and de Wolf F

Subjects
Drug Administration Schedule, Humans, Time Factors, Anti-HIV Agents administration & dosage, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, HIV Infections drug therapy
Abstract

Objective: CD4 cell count changes in therapy-naive patients were investigated during 7 years of highly active antiretroviral therapy (HAART) in an observational cohort., Methods: Three endpoints were studied: (1) time to >or=800 CD4 cells/mm in 5299 therapy-naive patients starting HAART, (2) CD4 cell count changes during 7 years of uninterrupted HAART in a subset of 544 patients, and (3) reaching a plateau in CD4 cell restoration after 5 years of HAART in 366 virologically suppressed patients., Results: Among patients with <50, 50 to 200, 200 to 350, 350 to 500, and >or=500 CD4 cells/mm at baseline, respectively, 20%, 26%, 46%, 73%, and 87% reached >or=800 CD4 cells/mm within 7 years of starting HAART. Periods with HIV RNA levels >500 copies/mL and age >or=50 years were associated with lesser increases in CD4 cell counts between 6 months and 7 years. Having reached >or=800 CD4 cells/mm at 5 years, age >or=50 years, and >or=1 HIV RNA measurement >1000 copies/mL between 5 and 7 years were associated with a plateau in CD4 cell restoration., Conclusions: Restoration to CD4 cell counts >or=800 cells/mm is feasible within 7 years of HAART in most HIV-infected patients starting with >or=350 cells/mm and achieving sufficient suppression of viral replication. Particularly in patients >or=50 years of age, it may be beneficial to start earlier than current guidelines recommend.

Published
2007
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