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1. Optimal timing of antiretroviral treatment initiation in HIV-positive children and adolescents: a multiregional analysis from Southern Africa, West Africa and Europe

Author

Schomaker, Michael, Leroy, Valeriane, Wolfs, Tom, Technau, Karl-Günter, Renner, Lorna, Judd, Ali, Sawry, Shobna, Amorissani-Folquet, Madeleine, Noguera-Julian, Antoni, Tanser, Frank, Eboua, Frančois, Navarro, Maria Luisa, Chimbetete, Cleophas, Amani-Bosse, Clarisse, Warszawski, Josiane, Phiri, Sam, N'Gbeche, Sylvie, Cox, Vivian, Koueta, Fla, Giddy, Janet, Sygnaté-Sy, Haby, Raben, Dorthe, Chêne, Geneviève, Davies, Mary-Ann, and on behalf of the IeDEAWest and Southern Africa regional collaborations and COHERE in EuroCoord

Subjects
Antiretroviral treatment, Epidemiology, G-formula, Paediatrics, paediatrics, causal inference, g-formula, Causal inference
Abstract

BACKGROUND: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents. METHODS: A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula. RESULTS: Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm 3 (394; 1037) (children aged = 1 and < 5 years), 373 (172; 630) (= 5 and < 10 years) and 238 (88; 425) (= 10 and < 16 years). There was a general trend towards lower mortality and better growth with earlier treatment initiation. In children < 10 years old at enrolment, by 5 years of follow-up there was lower mortality and a higher mean height-for-age z-score with immediate ART initiation versus delaying until CD4 count < 350 cells/mm 3 (or CD4% < 15% or weight-for-age z-score < -2) with absolute differences in mortality and height-for-age z-score of 0.3% (95% confidence interval: 0.1%; 0.6%) and -0.08 (-0.09; -0.06) (= 1 and < 5 years), and 0.3% (0.04%; 0.5%) and -0.07 (-0.08; -0.05) (= 5 and < 10 years). In those aged > 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and -0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes. CONCLUSIONS: Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive.

Published
2017

2. Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

Author

Chereau, Fanny, Madec, Yoann, Sabin, Caroline, Obel, Niels, Ruiz-Mateos, Ezequiel, Chrysos, Georgios, Fidler, Sarah, Lehmann, Clara, Zangerle, Robert, Wittkop, Linda, Reiss, Peter, Hamouda, Osamah, Perez, Vicente Estrada, Leal, Manuel, Mocroft, Amanda, De Olalla, Patricia Garcia, Ammassari, Adriana, Monforte, Antonella D'Arminio, Mussini, Cristina, Segura, Ferran, Castagna, Antonella, Cavassini, Matthias, Grabar, Sophie, Morlat, Philippe, De Wit, Stéphane, Lambotte, Olivier, Meyer, Laurence, Judd, Ali, Touloumi, Giota, Warszawski, Josiane, Dabis, François, Krause, Murielle Mary, Ghosn, Jade, Leport, Catherine, Wit, Ferdinand, Prins, Maria, Bucher, Heiner, Gibb, Diana, Fätkenheuer, Gerd, Del Amo, Julia, Thorne, Claire, Kirk, Ole, Stephan, Christoph, Pérez-Hoyos, Santiago, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Noguera-Julian, Antoni, Antinori, Andrea, Brockmeyer, Norbert, Prieto, Luis, Conejo, Pablo Rojo, Soriano-Arandes, Antoni, Battegay, Manuel, Kouyos, Roger, Tookey, Pat, Casabona, Jordi, Miró, Jose M., Konopnick, Deborah, Goetghebuer, Tessa, Sönnerborg, Anders, Torti, Carlo, Teira, Ramon, Garrido, Myriam, Haerry, David, Miró, Jose Ma, Costagliola, Dominique, D'Arminio-Monforte, Antonella, Raben, Dorthe, Chêne, Geneviève, Barger, Diana, Schwimmer, Christine, Termote, Monique, Campbell, Maria, Frederiksen, Casper M., Friis-Møller, Nina, Kjaer, Jesper, Brandt, Rikke Salbøl, Berenguer, Juan, Bohlius, Julia, Bouteloup, Vincent, Cozzi-Lepri, Alessandro, Davies, Mary-Anne, Dorrucci, Maria, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Rohner, Eliane, Schomaker, Michael, Smit, Colette, Sterne, Jonathan, Thiebaut, Rodolphe, Van Der Valk, Marc, Fanny, C, Yoann, M, Caroline, S, Niels, O, Ezequiel, R, Georgios, C, Sarah, F, Clara, L, Robert, Z, Linda, W, Peter, R, Osamah, H, Vicente Estrada, P, Manuel, L, Amanda, M, Patricia Garcia De, O, Adriana, A, Antonella D’Arminio, M, Cristina, M, Ferran, S, Antonella, C, Matthias, C, Sophie, G, Philippe, M, Stéphane De, W, Olivier, L, Laurence, M, Puoti, M, Chereau, F, Madec, Y, Sabin, C, Obel, N, Ruiz-Mateos, E, Chrysos, G, Fidler, S, Lehmann, C, Zangerle, R, Wittkop, L, Reiss, P, Hamouda, O, Perez, Ve, Leal, M, Mocroft, A, De Olalla, Pg, Ammassari, A, Monforte, Ada, Mussini, C, Segura, F, Castagna, A, Cavassini, M, Grabar, S, Morlat, P, De Wit, S, Lambotte, O, Meyer, L, The HIV Controllers Project Working Group for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in, Eurocoord, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), HIV Monitoring Foundation, Augustinus Foundation, European Commission, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), University College London Hospitals (UCLH), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Hospital Universitario Virgen del Rocío [Sevilla], Tzaneio General Hospital, Imperial College London, German Center for Infection Research - Partner Site Bonn-Cologne (DZIF), Universität Innsbruck [Innsbruck], Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Robert Koch Institute [Berlin] (RKI), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), CIBER de Epidemiología y Salud Pública (CIBERESP), Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), University of Milan, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Hospital Universitari Parc Taulí of Sabadell, Barcelona, Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Université de Lausanne (UNIL), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université libre de Bruxelles (ULB), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Université de Lausanne = University of Lausanne (UNIL), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), HAL UPMC, Gestionnaire, AII - Infectious diseases, APH - Aging & Later Life, Global Health, Amsterdam institute for Infection and Immunity, HIV Controllers Project Working Group for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCOORD, Imperial College Healthcare NHS Trust- BRC Funding, and Medical Research Council (MRC)

Subjects
Male, HIV Infections, CD8-Positive T-Lymphocytes, Pathology and Laboratory Medicine, Immunodeficiency Viruses, HIV-1/immunology, Public and Occupational Health, lcsh:Science, Adult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Female, HIV-1, Humans, Viral Load, Viremia, Virus Replication, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), virus diseases, CD8-Positive T-Lymphocytes/drug effects, Antiretroviral Therapy, Highly Active/methods, Medical Microbiology, Viral Pathogens, Science & Technology - Other Topics, Human, Blood cells, Immunology, HIV Infections/drug therapy, Virus Replication/immunology, Men WHO Have Sex with Men, Cytotoxic T cells, Microbiology, Viremia/drug therapy, Microbial Pathogens, Science & Technology, lcsh:R, Organisms, Biology and Life Sciences, Anti-HIV Agent, NATURAL-HISTORY, CD8-Positive T-Lymphocyte, Anti-HIV Agents/therapeutic use, HIV CD4 AIDS, T-CELLS, Population Groupings, lcsh:Q, Preventive Medicine, Sexuality Groupings, RNA viruses, RNA LEVELS, lcsh:Medicine, PROGRESSION, ACTIVATION, INFECTION, Cellular types, Medicine and Health Sciences, HIV Infection, Medicine (all), Immune cells, HIV diagnosis and management, ABSENCE, Vaccination and Immunization, Multidisciplinary Sciences, Infectious Diseases, CD4-Positive T-Lymphocyte, Viruses, White blood cells, Pathogens, Research Article, Cell biology, Evolutionary Immunology, Infectious Disease Control, General Science & Technology, T cells, Antiretroviral Therapy, CD4-Positive T-Lymphocytes/drug effects, CD4 Lymphocyte Count/methods, Viral Evolution, Antiviral Therapy, Virology, MD Multidisciplinary, Retroviruses, Evolutionary Biology, Lentivirus, HIV, Viral Load/drug effects, Diagnostic medicine, Organismal Evolution, Animal cells, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, REPLICATION, People and Places, Microbial Evolution, CD4-Positive T-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/virology, CD8-Positive T-Lymphocytes/immunology, HIV Infections/immunology, HIV Infections/virology, Viral Load/immunology, Viremia/immunology, Viremia/virology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, INVERSE PROBABILITY
Abstract

[Objective] HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control., [Methods] HICs were identified in COHERE on the basis of ≥5 consecutive viral loads (VL) ≤500 copies/mL over ≥1 year whilst ART-naive, with the last VL ≤500 copies/mL measured ≥5 years after HIV diagnosis. Loss of virological control was defined as 2 consecutive VL >2000 copies/mL. Duration of HIV control was described using cumulative incidence method, considering loss of virological control, ART initiation and death during virological control as competing outcomes. Factors associated with loss of virological control were identified using Cox models. CD4 and CD8 dynamics were described using mixed-effect linear models., [Results] We identified 1067 HICs; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds., [Discussion] Expansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. Our findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs., The COHERE study group has received unrestricted funding from: Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS), France; HIV Monitoring Foundation, The Netherlands; and the Augustinus Foundation, Denmark. The research leading to these results received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement n° 260694.

Published
2017
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3. Prevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children. A EuroCoord-CHAIN-EPPICC Joint project

Author

Ngo-Giang-Huong, Nicole, Ene, Luminita, Ramos, José Tomás, Cellerai, Cristina, Klimkait, Thomas, Brichard, Bénédicte, Valerius, Niels, Sabin, Caroline, Teira, Ramón, Obel, Niels, Stephan, Christoph, Wittkop, Linda, De Wit, Stéphane, Thorne, Claire, Gibb, Diana, Schwimmer, Christine, Campbell, Maria Athena, Pillay, Deenan, Lallemant, Marc, Rosenfeldt, Vibeke, Dabis, François, Judd, Ali, Reiss, Peter, Goetghebuer, Tessa, Duiculescu, Dan, Noguera-Julian, Antoni, Marczynska, Magdalena, Giacquinto, Carlo, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique, Amsterdam institute for Infection and Immunity, Amsterdam Public Health, Global Health, EuroCoord-CHAIN-EPPICC joint project study group, and The EuroCoord-CHAIN-EPPICC joint project study group

Subjects
0301 basic medicine, Male, endocrine system diseases, First-line combination antiretroviral therapy, HIV Infections, Drug resistance, Kaplan-Meier Estimate, Adolescent, Anti-HIV Agents/therapeutic use, CD4 Lymphocyte Count, Child, Child, Preschool, Drug Resistance, Viral/drug effects, Drug Resistance, Viral/genetics, Drug Therapy, Combination, Female, HIV Infections/drug therapy, HIV Infections/mortality, HIV Infections/virology, HIV-1/drug effects, Humans, Infant, Mutation, Reverse Transcriptase Inhibitors/therapeutic use, Viral Load/drug effects, Children, HIV, Pre-treatment drug resistance mutations, Virological failure, 0302 clinical medicine, Medical microbiology, Interquartile range, immune system diseases, 030212 general & internal medicine, Pathologie maladies infectieuses, virus diseases, Viral Load, 3. Good health, Infectious Diseases, Reverse Transcriptase Inhibitors, Viral load, Research Article, Cart, medicine.medical_specialty, Anti-HIV Agents, 030106 microbiology, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Internal medicine, mental disorders, Drug Resistance, Viral, medicine, lcsh:RC109-216, ddc:610, Proportional hazards model, business.industry, Confidence interval, eye diseases, Regimen, nervous system, Immunology, HIV-1, sense organs, business
Abstract

Background: Few studies have evaluated the impact of pre-treatment drug resistance (PDR) on response to combination antiretroviral treatment (cART) in children. The objective of this joint EuroCoord-CHAIN-EPPICC/PENTA project was to assess the prevalence of PDR mutations and their association with virological outcome in the first year of cART in children. Methods: HIV-infected children 500 copies/mL after 6 months cART and was assessed by Cox proportional hazards models. All models were adjusted for baseline demographic, clinical, immunology and virology characteristics and calendar period of cART start and initial cART regimen. Results: Of 476 children, 88 % were vertically infected. At cART initiation, median (interquartile range) age was 6.6 years (2.1-10.1), CD4 cell count 297 cells/mm3 (98-639), and HIV-RNA 5.2 log10copies/mL (4.7-5.7). Of 37 children (7.8 %, 95 % confidence interval (CI), 5.5-10.6) harboring a virus with ≥1 PDR mutations, 30 children had a virus resistant to ≥1 of the prescribed drugs. Overall, the cumulative Kaplan-Meier estimate for virological failure was 19.8 % (95 %CI, 16.4-23.9). Cumulative risk for VF tended to be higher among children harboring a virus with PDR and resistant to ≥1 drug prescribed than among those receiving fully active cART: 32.1 % (17.2-54.8) versus 19.4 % (15.9-23.6) (P = 0.095). In multivariable analysis, age was associated with a higher risk of VF with a 12 % reduced risk per additional year (HR 0.88; 95 %CI, 0.82-0.95; P < 0.001). Conclusions: PDR was not significantly associated with a higher risk of VF in children in the first year of cART. The risk of VF decreased by 12 % per additional year at treatment initiation which may be due to fading of PDR mutations over time. Lack of appropriate formulations, in particular for the younger age group, may be an important determinant of virological failure., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2016

4. Children and young people with perinatal HIV in Europe: epidemiological situation in 2014 and implications for the future

Author

del Amo, Julia, Conejo, Pablo Rojo, Sabin, Caroline, Warszawski, Josiane, Gennotte, Anne-Francoise, Nadal, David, Gibb, Diana, Judd, Ali, Thorne, Claire, Olson, Ashley, Lodi, Sara, Pantazis, Nikos, Termote, Monique, Ledergerber, Bruno, Kristensen, Dennis, Brandt, Rikke Salbøl, Saidi, Yacine, Burns, Fiona, Chêne, Geneviève, Costagliola, Dominique, Giaquinto, Carlo, Grarup, Jesper, Kirk, Ole, Meyer, Laurence, Bailey, Heather, Anne, Alain Volny, Panteleev, Alex, Phillips, Andrew, Porter, Kholoud, Aboulker, Jean-Pierre, Albert, Jan, Asandi, Silvia, Monforte, Antonella d'Arminio, de Wit, Stéphane, Reiss, Peter, Gatell, José, Clínic, Fundació Privada, Bíomèdica, Recerca, Hamouda, Osamah, Karpov, Igor, Lundgren, Jens, Malyuta, Ruslan, Møller, Claus, Prins, Maria, Rakhmanova, Aza, Rockstroh, Jürgen, Rosinska, Magda, Sandhu, Manjinder, Touloumi, Giota, Cooper, David, Global Health, and Infectious diseases

Subjects
Adult, medicine.medical_specialty, Adolescent, Epidemiology, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Perinatal hiv, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Virology, Environmental health, Surveys and Questionnaires, Journal Article, Medicine, Humans, 030212 general & internal medicine, 030505 public health, business.industry, Research Support, Non-U.S. Gov't, Public Health, Environmental and Occupational Health, Infant, Newborn, Infectious Disease Transmission, Vertical, Europe, Cohort, Female, 0305 other medical science, business
Abstract

Accurate ascertainment of the number of children living with human immunodeficiency virus (HIV) is important to plan paediatric and adolescent health services. In Europe, the first generation of perinatally HIV-infected survivors are transferring to adult care and their health needs are unknown. We undertook an online survey of HIV cohort studies participating in the EuroCoord Network of Excellence to ascertain the number of perinatally HIV-infected (pHIV) patients included, to compare it with those published by the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) and to assess the ability of countries to follow up pHIV patients after transfer to adult care. At the end of 2013, 16 countries in EuroCoord reported 8,229 pHIV patients in follow-up in cohorts, compared with 5,160 cumulative diagnoses reported by the ECDC in the same area. Follow-up of pHIV patients after transfer to adult care varied. It is likely that the number of diagnoses of perinatal HIV reported to ECDC is an underestimate, although this varies by country. Further work is needed to refine estimates and encourage follow-up in adult HIV cohorts to investigate long-term outcomes and improve the care of the next generation of children with HIV.

Published
2015
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5. Prognosis of HIV-associated non-Hodgkin lymphoma in patients starting combination antiretroviral therapy

Author

Bohlius, Julia, Schmidlin, Kurt, Costagliola, Dominique, Fätkenheuer, Gerd, May, Margaret, Murillo, Ana Maria Caro, Mocroft, Amanda, Bonnet, Fabrice, Clifford, Gary, Touloumi, Giota, Miro, Jose M., Chene, Genevieve, Lundgren, Jens, Egger, Matthias, Antinori, Andrea, Boué, François, Brockmeyer, Norbert, Casabona, Jordi, Lopez-Guillermo, Armando, Ribera, Josep Maria, Dronda, Fernando, Obel, Niels, Fisher, Martin, Franceschi, Silvia, Gibb, Diana, Le Moing, Vincent, Nadal, David, Prins, Maria, Raffi, François, Roca, Bernardino, Verbon, Annelies, Wolf, Timo, Fortuny, Claudia, Chakraborty, Rana, Minder, Christoph, Sterne, Jonathan, Zwahlen, Marcel, Ellefson, Michelle, Kjaer, Jesper, Collin, Fidéline, Colin, Céline, Weller, Ian, Ledergerber, Bruno, Warszawski, Josiane, Meyer, Laurence, Dabis, François, Krause, Murielle Mary, Goujard, Cecile, Leport, Catherine, de Wolf, Frank, Reiss, Peter, Porter, Kholoud, Dorrucci, Maria, Sabin, Caroline, Del Amo, Julia, Thorne, Claire, Kirk, Ole, Staszewski, Schlomo, Perez-Hoyos, Santiago, Almeda, Jesus, D'Arminio Monforte, Antonella, de Martino, Maurizio, Ramos, Jose, Battegay, Manuel, Mussini, Cristina, Tookey, Pat, Castagna, Antonella, de Wit, Stephane, Torti, Carlo, Teira, Ramon, Garrido, Myriam, Dedes, Nikos, Phillips, Andrew, Furrer, Hansjakob, Newell, Marie Louise, Telenti, Amalio, Pantazis, Nikos, Lechenadec, Jérôme, Boufassa, Faroudy, Tran, Laurent, Balestre, Eric, Lanoy, Emilie, Couturier, Françoise, Rispens, Theo, Gras, Luuk A.J., Bhaskaran, Krishnan, Hill, Teresa, Judd, Ali, Duong, Trinh, Sobrino, Paz, Jennings, Beverley, Bonfigli, Sandro, Cozzi-Lepri, Alessandro, Corvasce, Stefano, Adorni, Fulvio, Ridolfo, Anna Lisa, Paraninfo, Giuseppe, Keiser, Olivia, Borghi, Vanni, Weller, Ian, Costagliola, Dominique, Ledergerber, Bruno, Lundgren, Jen, Chene, Genevieve, Touloumi, Giota, Warszawski, Josiane, Meyer, Laurence, Dabis, Francoi, Krause Murielle, Mary, Leport, Catherine, de Wolf, Frank, Reiss, Peter, Porter, Kholoud, Dorrucci, Maria, Sabin, Caroline, Gibb, Diana, Del Amo, Julia, Obel, Niel, Thorne, Claire, Mocroft, Amanda, Kirk, Ole, Staszewski, Schlomo, Perez Hoyos, Santiago, Almeda, Jesu, Antinori, Andrea, Monforte A., D'Arminio, de Martino, Maurizio, Brockmeyer, Norbert, Faetkenheuer, Gerd, Ramos, Jose, Battegay, Manuel, Mussini, Cristina, Tookey, Pat, Casabona, Jordi, Miro Jose, M., Castagna, Antonella, de Wit, Stephane, Torti, Carlo, Teira, Ramon, Garrido, Myriam, Dedes, Niko, Phillips, Andrew, Furrer, Hansjakob, Egger, Matthia, Newell Marie, Louise, Sterne, Jonathan, Telenti, Amalio, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, and Infectious diseases

Subjects
Cart, Adult, Male, medicine.medical_specialty, Adolescent, Immunology, AIDS-related lymphoma, Young Adult, immune system diseases, Internal medicine, hemic and lymphatic diseases, Antiretroviral Therapy, Highly Active, Epidemiology, medicine, Immunology and Allergy, Humans, Young adult, Mortality, Prospective cohort study, Collaborative study, Immunodeficiency, Non-Hodgkin lymphoma, Lymphoma, AIDS-Related, business.industry, Lymphoma, Non-Hodgkin, Middle Aged, medicine.disease, Prognosis, Surgery, Lymphoma, Antiretroviral therapy, CD4 Lymphocyte Count, Europe, Infectious Diseases, Treatment Outcome, HIV-1, Cohort studies, Female, business, Epidemiologic Methods, Cohort study
Abstract

Objective: We examined survival and prognostic factors of patients who developed HIV-associated non-Hodgkin lymphoma (NHL) in the era of combination antiretroviral therapy (cART). Design and setting: Multicohort collaboration of 33 European cohorts. Methods: We included all cART-naive patients enrolled in cohorts participating in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who were aged 16 years or older, started cART at some point after 1 January 1998 and developed NHL after 1 January 1998. Patients had to have a CD4 cell count after 1 January 1998 and one at diagnosis of the NHL. Survival and prognostic factors were estimated using Weibull models, with random effects accounting for heterogeneity between cohorts. Results: Of 67 659 patients who were followed up during 304 940 person-years, 1176 patients were diagnosed with NHL. Eight hundred and forty-seven patients (72%) from 22 cohorts met inclusion criteria. Survival at 1 year was 66% [95% confidence interval (CI) 63-70%] for systemic NHL (n = 763) and 54% (95% CI: 43-65%) for primary brain lymphoma (n = 84). Risk factors for death included low nadir CD4 cell counts and a history of injection drug use. Patients developing NHL on cART had an increased risk of death compared with patients who were cART naive at diagnosis. Conclusion: In the era of cART two-thirds of patients diagnosed with HIV-related systemic NHL survive for longer than 1 year after diagnosis. Survival is poorer in patients diagnosed with primary brain lymphoma. More advanced immunodeficiency is the dominant prognostic factor for mortality in patients with HIV-related NHL.

Published
2009
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6. The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis

Author

The Collaborative Initiative For Paediatric HIV Education And Research (CIPHER) Global Cohort Collaboration, Slogrove, Amy L., Schomaker, Michael, Davies, Mary-Ann, Williams, Paige, Balkan, Suna, Ben-Farhat, Jihane, Calles, Nancy, Chokephaibulkit, Kulkanya, Duff, Charlotte, Eboua, Tanoh Francois, Kekitiinwa-Rukyalekere, Adeodata, Maxwell, Nicola, Pinto, Jorge, Seage III, George R., Teasdale, Chloe A., Wanless, Sebastian, Warszawski, Josiane, Wools-Kaloustian, Kara, Yotebieng, Marcel, Timmerman, Venessa, Collins, Intira J., Goodall, Ruth, Smith, Colette, Patel, Kunjal, Paul, Mary E., Gibb, Diana, Vreeman, Rachel, Abrams, Elaine J., Hazra, Rohan, Van Dyke, Russell, Bekker, Linda-Gail, Mofenson, Lynne, Vicari, Marissa, Essajee, Shaffiq, Penazzato, Martina, Anabwani, Gabriel, Mohapi, Edith Q., Kazembe, Peter N., Hlatshwayo, Makhosazana, Lumumba, Mwita, Goetghebuer, Tessa, Thorne, Claire, Galli, Luisa, Van Rossum, Annemarie, Giaquinto, Carlo, Marczynska, Magdalena, Marques, Laura, Prata, Filipa, Ene, Luminita, Okhonskaia, Liubov, Rojo, Pablo, Fortuny, Claudia, Naver, Lars, Rudin, Christoph, Le Coeur, Sophie, Volokha, Alla, Rouzier, Vanessa, Succi, Regina, Sohn, Annette, Kariminia, Azar, Edmonds, Andrew, Lelo, Patricia, Ayaya, Samuel, Ongwen, Patricia, Jefferys, Laura F., Phiri, Sam, Mubiana-Mbewe, Mwangelwa, Sawry, Shobna, Renner, Lorna, Sylla, Mariam, Abzug, Mark J., Levin, Myron, Oleske, James, Chernoff, Miriam, Traite, Shirley, Purswani, Murli, Chadwick, Ellen G., Judd, Ali, and Leroy, Valeriane

Subjects
Epidemiology, Cohort analysis, Teenagers, 3. Good health
Abstract

Background Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in “real-life” settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Methods and findings Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5–5.2) years for the total cohort and 6.4 (3.6–8.0) years in Europe, 3.7 (2.0–5.4) years in North America, 2.5 (1.2–4.4) years in South and Southeast Asia, 5.0 (2.7–7.5) years in South America and the Caribbean, and 2.1 (0.9–3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3–2.1) years in North America to 7.1 (5.3–8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4–2.6) years in North America to 7.9 (6.0–9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%–2.8%), 15.6% (15.1%–16.0%), and 11.3% (10.9%–11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%–1.1%]) and highest in South America and the Caribbean (4.4% [3.1%–6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%–6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%–13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. Conclusion To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses.

7. Additional file 2: of Prevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children â a EuroCoord-CHAIN-EPPICC joint project

Author

Ngo-Giang-Huong, Nicole, Wittkop, Linda, Judd, Ali, Reiss, Peter, Goetghebuer, Tessa, Duiculescu, Dan, Noguera-Julian, Antoni, Marczynska, Magdalena, Giacquinto, Carlo, Luminita Ene, Ramos, Jose, Cellerai, Cristina, Klimkait, Thomas, Brichard, Benedicte, Valerius, Niels, Sabin, Caroline, Teira, Ramon, Obel, Niels, Stephan, Christoph, StĂŠphane De Wit, Thorne, Claire, Gibb, Diana, Schwimmer, Christine, Campbell, Maria, Deenan Pillay, and Lallemant, Marc

Subjects
3. Good health
Abstract

Crude Hazard Ratios (cHR) and adjusted Hazard Ratios (aHR) for the association between PDR and resistant group versus no PDR/susceptible group from Cox proportional Hazards models stratified by initial cART regimen. HR in the overall group are also presented in more details in Table 3 of the article. All models were adjusted for sex, age, pre-treatment viral load (log10 transformed) and CD4 count, subtype, region of origin, year of treatment start, previous AIDS diagnosis and HIV transmission risk group. (DOCX 46 kb)

8. Additional file 1: of Prevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children â a EuroCoord-CHAIN-EPPICC joint project

Author

Ngo-Giang-Huong, Nicole, Wittkop, Linda, Judd, Ali, Reiss, Peter, Goetghebuer, Tessa, Duiculescu, Dan, Noguera-Julian, Antoni, Marczynska, Magdalena, Giacquinto, Carlo, Luminita Ene, Ramos, Jose, Cellerai, Cristina, Klimkait, Thomas, Brichard, Benedicte, Valerius, Niels, Sabin, Caroline, Teira, Ramon, Obel, Niels, Stephan, Christoph, StĂŠphane De Wit, Thorne, Claire, Gibb, Diana, Schwimmer, Christine, Campbell, Maria, Deenan Pillay, and Lallemant, Marc

Subjects
3. Good health
Abstract

Characteristics at cART initiation according to presence/absence of PDR. Table. (DOCX 20Â kb)

9. Response to combination antiretroviral therapy: variation by age - The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study group

Author

Sabin, Caroline A., Smith, Colette J., Monforte, Antonella D. Arminio, Battegay, Manuel, Gabiano, Clara, Galli, Luisa, Geelen, Sibyl, Gibb, Diana, Guiguet, Marguerite, Judd, Ali, Leport, Catherine, Dabis, Francois, Pantazis, Nikos, Porter, Kholoud, Raffi, Francois, Thorne, Claire, Torti, Carlo, Walker, Sarah, Warszawski, Josiane, Wintergerst, Uwe, Chene, Genevieve, Jens Lundgren, Weller, Ian, Costagliola, Dominique, Ledergerber, Bruno, Lundgren, Jens, Touloumi, Giota, Meyer, Laurence, Krause, Murielle Mary, Goujard, Cecile, Wolf, Frank, Reiss, Peter, Dorrucci, Maria, Sabin, Caroline, Del Amo, Julia, Obel, Niels, Mocroft, Amanda, Kirk, Ole, Staszewski, Schlomo, Perez-Hoyos, Santiago, Almeda, Jesus, Antinori, Andrea, Tovo, Pier-Angelo, Salzberger, Bernd, Fatkenheuer, Gerd, Ramos, Jose, Mussini, Cristina, Tookey, Pat, Casabona, Jordi, Miro, Jose M., Castagna, Antonella, Wit, Stephane, Teira, Ramon, Garrido, Myriam, Dedes, Nikos, Phillips, Andrew, Furrer, Hansjakob, Egger, Matthias, Newell, Marie-Louise, Sterne, Jonathan, and Telenti, Amalio

10. Additional file 2: of Prevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children â a EuroCoord-CHAIN-EPPICC joint project

Author

Ngo-Giang-Huong, Nicole, Wittkop, Linda, Judd, Ali, Reiss, Peter, Goetghebuer, Tessa, Duiculescu, Dan, Noguera-Julian, Antoni, Marczynska, Magdalena, Giacquinto, Carlo, Luminita Ene, Ramos, Jose, Cellerai, Cristina, Klimkait, Thomas, Brichard, Benedicte, Valerius, Niels, Sabin, Caroline, Teira, Ramon, Obel, Niels, Stephan, Christoph, StĂŠphane De Wit, Thorne, Claire, Gibb, Diana, Schwimmer, Christine, Campbell, Maria, Deenan Pillay, and Lallemant, Marc

Subjects
3. Good health
Abstract

Crude Hazard Ratios (cHR) and adjusted Hazard Ratios (aHR) for the association between PDR and resistant group versus no PDR/susceptible group from Cox proportional Hazards models stratified by initial cART regimen. HR in the overall group are also presented in more details in Table 3 of the article. All models were adjusted for sex, age, pre-treatment viral load (log10 transformed) and CD4 count, subtype, region of origin, year of treatment start, previous AIDS diagnosis and HIV transmission risk group. (DOCX 46 kb)

11. Additional file 1: of Prevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children â a EuroCoord-CHAIN-EPPICC joint project

Author

Ngo-Giang-Huong, Nicole, Wittkop, Linda, Judd, Ali, Reiss, Peter, Goetghebuer, Tessa, Duiculescu, Dan, Noguera-Julian, Antoni, Marczynska, Magdalena, Giacquinto, Carlo, Luminita Ene, Ramos, Jose, Cellerai, Cristina, Klimkait, Thomas, Brichard, Benedicte, Valerius, Niels, Sabin, Caroline, Teira, Ramon, Obel, Niels, Stephan, Christoph, StĂŠphane De Wit, Thorne, Claire, Gibb, Diana, Schwimmer, Christine, Campbell, Maria, Deenan Pillay, and Lallemant, Marc

Subjects
3. Good health
Abstract

Characteristics at cART initiation according to presence/absence of PDR. Table. (DOCX 20Â kb)

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