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103. Mortality in patients with HIV-1 infection starting antiretroviral therapy in south Africa, Europe, or North America: a collaborative analysis of prospective studies

Author

Boulle, Andrew, Schomaker, Michael, May, Margaret T., Hogg, Robert S., Shepherd, Bryan E., Monge, Susana, Keiser, Olivia, Lampe, Fiona C., Giddy, Janet, Ndirangu, James, Garone, Daniela, Fox, Matthew, Ingle, Suzanne M., Reiss, Peter, Dabis, Francois, Costagliola, Dominique, Castagna, Antonella, Ehren, Kathrin, Campbell, Colin, Gill, M. John, Saag, Michael, Justice, Amy C., Guest, Jodie, Crane, Heidi M., Egger, Matthias, and Sterne, Jonathan A.C.

Subjects
Mortality -- Analysis -- Risk factors -- North America -- Europe -- South Africa, Antiviral agents -- Health aspects, Highly active antiretroviral therapy -- Health aspects, HIV patients -- Care and treatment, HIV infection -- Patient outcomes -- Analysis -- Drug therapy -- Research, Biological sciences
Abstract

Background: High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Methods and Findings: Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 20012010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/ml in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count Conclusions: After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary., Introduction Antiretroviral therapy (ART) for HIV-infected patients has been routinely available in some Sub-Saharan African settings for more than a decade. Early analyses of treatment cohorts in this region focussed [...]

Published
2014
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104. When to start antiretroviral therapy in children aged 2-5 years: a collaborative causal modelling analysis of cohort studies from Southern Africa

Author

Schomaker, Michael, Egger, Matthias, Ndirangu, James, Phiri, Sam, Moultrie, Harry, Technau, Karl, Cox, Vivian, Giddy, Janet, Chimbetete, Cleophas, Wood, Robin, Gsponer, Thomas, Moore, Carolyn Bolton, Rabie, Helena, Eley, Brian, Muhe, Lulu, Penazzato, Martina, Essajee, Shaffiq, Keiser, Olivia, and Davies, Mary-Ann

Subjects
Health promotion -- Management, Antiviral agents -- Dosage and administration, Children -- Health aspects, Company business management, Biological sciences
Abstract

Background: There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2-5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2-5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count < 750 cells/[mm.sup.3] or CD4 percentage (CD4%) < 25%. Methods and Findings: ART-naive children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and [greater than or equal to] 1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6;4.1), with a median (first; third quartile) CD4 count of 592 cells/[mm.sup.3] (356;895) and median (first;third quartile) CD4% of 16% (10%;23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1-6.5) (no ART) to 2.1% (95% CI: 1.3%-3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count < 750 cells/[mm.sup.3] or CD4% Conclusions:The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count < 750 cells/[mm.sup.3] or CD4% Please see later in the article for the Editors' Summary., Introduction HIV infection continues to contribute substantially to the burden of disease in children, with an estimated 330,000 new paediatric infections worldwide in 2011. Paediatric antiretroviral combination therapy (ART) is [...]

Published
2013
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105. Chronic Hepatitis B and C Virus Infection and Risk for Non-Hodgkin Lymphoma in HIV-Infected Patients: A Cohort Study

Author

Wang, Qing, De Luca, Andrea, Smith, Colette, Zangerle, Robert, Sambatakou, Helen, Bonnet, Fabrice, Smit, Colette, Schommers, Philipp, Thornton, Alicia, Berenguer, Juan, Peters, Lars, Spagnuolo, Vincenzo, Ammassari, Adriana, Antinori, Andrea, Roldan, Eugenia Quiros, Mussini, Cristina, Miro, Jose M., Konopnicki, Deborah, Fehr, Jan, Campbell, Maria A., Termote, Monique, Bucher, Heiner C., De Wit, Stéphane, Costagliola, Dominique, D'Arminio-Monforte, Antonella, Castagna, Antonella, Del Amo, Julia, Mocroft, Amanda, Raben, Dorthe, Chêne, Geneviève, Touloumi, Giota, Warszawski, Josiane, Meyer, Laurence, Dabis, François, Krause, Murielle Mary, Ghosn, Jade, Leport, Catherine, Wittkop, Linda, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Sabin, Caroline, Gibb, Diana, Fätkenheuer, Gerd, Obel, Niels, Thorne, Claire, Kirk, Ole, Stephan, Christoph, Pérez-Hoyos, Santiago, Hamouda, Osamah, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Noguera-Julian, Antoni, D'Arminio Monforte, Antonella, Brockmeyer, Norbert, Prieto, Luis, Conejo, Pablo Rojo, Soriano-Arandes, Antoni, Battegay, Manuel, Rauch, Andri, Tookey, Pat, Casabona, Jordi, Goetghebuer, Tessa, Sönnerborg, Anders, Torti, Carlo, Teira, Ramon, Garrido, Myriam, Haerry, David, Bohlius, Julia, Bouteloup, Vincent, Cozzi-Lepri, Alessandro, Davies, Mary-Anne, Dorrucci, Maria, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Grabar, Sophie, Judd, Ali, Lambotte, Olivier, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Schomaker, Michael, Sterne, Jonathan, Thiebaut, Rodolphe, Van Der Valk, Marc, Wyss, Natasha, Barger, Diana, Schwimmer, Christine, Friis-Møller, Nina, Kjaer, Jesper, Brandt, Rikke Salbøl, Wang, Q, De Luca, A, Smith, C, Zangerle, R, Sambatakou, H, Bonnet, F, Smit, C, Schommers, P, Thornton, A, Berenguer, J, Peters, L, Spagnuolo, V, Ammassari, A, Antinori, A, Roldan, E, Mussini, C, Miro, J, Konopnicki, D, Fehr, J, Campbell, M, Termote, M, Bucher, H, Puoti, M, University of Zurich, Bucher, Heiner C, Quiros Roldan, E, Miro, Jm, Campbell, Ma, Bucher, Hc, on behalf of The Hepatitis Coinfection and Non Hodgkin Lymphoma project team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in, Eurocoord, and Castagna, Antonella

Subjects
Male, Lymphoma, Hepatitis B Surface Antigen, HIV Infections, medicine.disease_cause, Cohort Studies, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, Risk Factors, HIV Infection, 030212 general & internal medicine, Viral, Chronic, media_common, Incidence (epidemiology), Hepatitis B Core Antigen, Lymphoma, Non-Hodgkin, Hazard ratio, virus diseases, General Medicine, Hepatitis C, Hepatitis B, Hepatitis B Core Antigens, Hepatitis Antibodie, 030220 oncology & carcinogenesis, RNA, Viral, Female, hepatitis c and b, Cohort study, Human, Adult, medicine.medical_specialty, Anti-HIV Agents, Biomarkers, Hepatitis Antibodies, Hepatitis B Surface Antigens, Hepatitis B, Chronic, Hepatitis C, Chronic, Humans, Immunoglobulin G, Hepatitis C virus, Non-Hodgkin, 610 Medicine & health, Settore MED/17 - MALATTIE INFETTIVE, 03 medical and health sciences, Internal medicine, Internal Medicine, medicine, media_common.cataloged_instance, HIV HCV NHL HBV, European union, Hepatitis B virus, business.industry, Risk Factor, Anti-HIV Agent, Biomarker, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), medicine.disease, digestive system diseases, 2724 Internal Medicine, Immunology, RNA, Cohort Studie, business
Abstract

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear. Objective: To investigate whether chronic HBV and HCV infection are associated with increased incidence of NHL in HIV-infected patients. Design: Cohort study. Setting: 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Patients: HIV-infected patients with information on HBV surface antigen measurements and detectable HCV RNA, or a positive HCV antibody test result if HCV RNA measurements were not available. Measurements: Time-dependent Cox models to assess risk for NHL in treatment-naive patients and those initiating ART, with inverse probability weighting to control for informative censoring. Results: A total of 52 479 treatment-naive patients (1339 [2.6%] with chronic HBV infection and 7506 [14.3%] with HCV infection) were included, of whom 40 219 (77%) later started ART. The median follow-up was 13 months for treatment-naive patients and 50 months for those receiving ART. A total of 252 treatment-naive patients and 310 treated patients developed NHL, with incidence rates of 219 and 168 cases per 100 000 person-years, respectively. The hazard ratios for NHL with HBV and HCV infection were 1.33 (95% CI, 0.69 to 2.56) and 0.67 (CI, 0.40 to 1.12), respectively, in treatment-naive patients and 1.74 (CI, 1.08 to 2.82) and 1.73 (CI, 1.21 to 2.46), respectively, in treated patients. Limitation: Many treatment-naive patients later initiated ART, which limited the study of the associations of chronic HBV and HCV infection with NHL in this patient group. Conclusion: In HIV-infected patients receiving ART, chronic co-infection with HBV and HCV is associated with an increased risk for NHL. Primary Funding Source: European Union Seventh Framework Programme.

Published
2017

106. 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

107. CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients: A multinational, multicohort European study

Author

Wittkop, Linda, Arsandaux, Julie, Trevino, Ana, van der Loeff, Maarten Schim, Anderson, Jane, van Sighem, Ard, Böni, Jürg, Brun-Vezinet, Françoise, Soriano, Vicente, Boufassa, Faroudy, Brockmeyer, Norbert, Calmy, Alexandra, Dabis, François, Jarrin, Inma, Dorrucci, Maria, Duque, Vitor, Fätkenheuer, Gerd, Zangerle, Robert, Ferrer, Elena, Porter, Kholoud, Judd, Ali, Sipsas, Nikolaos V., Lambotte, Olivier, Shepherd, Leah, Leport, Catherine, Morrison, Charles, Mussini, Cristina, Obel, Niels, Ruelle, Jean, Schwarze-Zander, Carolyne, Sonnerborg, Anders, Teira, Ramon, Torti, Carlo, Valadas, Emilia, Colin, Celine, Friis-Møller, Nina, Costagliola, Dominique, Thiebaut, Rodolphe, Chene, Geneviève, Matheron, Sophie, Touloumi, Giota, Warszawski, Josiane, Meyer, Laurence, Krause, Murielle Mary, Ghosn, Jade, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Bucher, Heiner, Gibb, Diana, Del Amo, Julia, Thorne, Claire, Mocroft, Amanda, Kirk, Ole, Stephan, Christoph, Pérez-Hoyos, Santiago, Hamouda, Osamah, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Noguera-Julian, Antoni, Antinori, Andrea, Monforte, Antonella d'Arminio, Prieto, Luis, Conejo, Pablo Rojo, Soriano-Arandes, Antoni, Battegay, Manuel, Kouyos, Roger, Tookey, Pat, Casabona, Jordi, Mirò, Jose M., Castagna, Antonella, Konopnick, Deborah, Goetghebuer, Tessa, Sönnerborg, Anders, Sabin, Caroline, Garrido, Myriam, Haerry, David, Berenguer, Juan, Bohlius, Julia, Bouteloup, Vincent, Cozzi-Lepri, Alessandro, Davies, Mary-Anne, Amo, Julia del, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Grabar, Sophie, Leroy, Valériane, Lodi, Sara, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Schomaker, Michael, Smit, Colette, Sterne, Jonathan, van der Valk, Marc, Wyss, Natasha, Epidémiologie et Biostatistique, Institut National de la Santé et de la Recherche Médicale (INSERM), Team MORPH3EUS (INSERM U1219 - UB - ISPED), 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 de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Infectious Diseases, Hospital Carlos III, Center for Infection and Immunity Amsterdam - CINIMA [Amsterdam, The Netherlands], Homerton University Hospital, Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), Universität Zürich [Zürich] = University of Zurich (UZH), Université Paris Diderot - Paris 7 (UPD7), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en épidémiologie et santé des populations (CESP), 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), Ruhr-Universität Bochum [Bochum], Geneva University Hospital (HUG), CHU de Bordeaux Pellegrin [Bordeaux], Instituto de Salud Carlos III [Madrid] (ISC), CIBER de Epidemiología y Salud Pública (CIBERESP), Istituto Superiore di Sanità (ISS), Hospitais da Universidade de Coimbra (H.U.C.), University of Coimbra [Portugal] (UC), University Hospital of Cologne [Cologne], Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Hospitalet de Llobregat, University College of London [London] (UCL), National and Kapodistrian University of Athens (NKUA), Service de Médecine Interne et Immunologie clinique [AP-HP Hôpital Bicêtre], Hôpital Bicêtre, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), FHI 360, Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Université Catholique de Louvain = Catholic University of Louvain (UCL), University Hospital Bonn, Department of Infectious Diseases, Institution of Medicine, Karolinska University Hospital and Karolinska Institutet, Sierrallana Hospital, Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), Universidade de Lisboa = University of Lisbon (ULISBOA), 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), CHU Bordeaux [Bordeaux], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Infectious diseases, Wittkop, L, Arsandaux, J, Trevino, A, van der Loeff, M, Anderson, J, van Sighem, A, Böni, J, Brun-Vezinet, F, Soriano, V, Boufassa, F, Brockmeyer, N, Calmy, A, Dabis, F, Jarrin, I, Dorrucci, M, Duque, V, Fätkenheuer, G, Zangerle, R, Ferrer, E, Porter, K, Judd, A, Sipsas, N, Lambotte, O, Shepherd, L, Leport, C, Morrison, C, Mussini, C, Obel, N, Ruelle, J, Schwarze-Zander, C, Sonnerborg, A, Teira, R, Torti, C, Valadas, E, Colin, C, Friis-Møller, N, Costagliola, D, Thiebaut, R, Chene, G, Matheron, S, Touloumi, G, Warszawski, J, Meyer, L, Krause, M, Ghosn, J, Reiss, P, Wit, F, Prins, M, Bucher, H, Gibb, D, Del Amo, J, Thorne, C, Mocroft, A, Kirk, O, Stephan, C, Pérez-Hoyos, S, Hamouda, O, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, Monforte, A, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Tookey, P, Casabona, J, Mirò, J, Castagna, A, Konopnick, D, Goetghebuer, T, Sönnerborg, A, Sabin, C, Garrido, M, Haerry, D, Berenguer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Amo, J, Dunn, D, Egger, M, Furrer, H, Guiguet, M, Grabar, S, Leroy, V, Lodi, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Schomaker, M, Smit, C, Sterne, J, van der Valk, M, Wyss, N, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto Superiore di Sanita [Rome], Gestionnaire, Hal Sorbonne Université, Wittkop, Linda, Arsandaux, Julie, Trevino, Ana, Van Der Loeff V Schim, Maarten, Anderson, Jane, Van Sighem, Ard, Jurg, Boni, Brun-Vezinet, Francoise, Soriano, Vicente, Boufassa, Faroudy, Brockmeyer, Norbert, Calmy, Alexandra, Dabis, Francoi, Jarrin, Inma, Dorrucci, Maria, Duque, Vitor, Fãtkenheuer, Gerd, Zangerle, Robert, Ferrer, Elena, Porter, Kholoud, Judd, Ali, Sipsas, Nikolaos V, Lambotte, Olivier, Shepherd, Leah, Leport, Catherine, Morrison, Charle, Mussini, Cristina, Obel, Niel, Ruelle, Jean, Schwarze-Zander, Carolyne, Sonnerborg, Ander, Teira, Ramon, Torti, Carlo, Valadas, Emilia, Colin, Celine, Friis-Moller, Nina, Costagliola, Dominique, Thiebaut, Rodolphe, Chene, Geneviève, Matheron, Sophie, on behalf of the COHERE in EuroCoord and ACHIeV2e Study, Group, and Castagna, Antonella

Subjects
0301 basic medicine, CD4-Positive T-Lymphocytes, Male, Internationality, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Gastroenterology, Anti-HIV Agents/administration & dosage/adverse effects/therapeutic use, Viral/blood, Cohort Studies, 0302 clinical medicine, CD4 HIV, Pharmacology (medical), 030212 general & internal medicine, Cd4 cell count, ddc:616, Confounding, virus diseases, Middle Aged, Viral Load, 3. Good health, [SDV] Life Sciences [q-bio], Europe, HIV-2/drug effects, Infectious Diseases, HIV-1/drug effects, RNA, Viral, Female, Viral load, Cohort study, Microbiology (medical), Cart, Adult, medicine.medical_specialty, Anti-HIV Agents, 030106 microbiology, 03 medical and health sciences, Internal medicine, medicine, Humans, Pharmacology, business.industry, CD4-Positive T-Lymphocytes/immunology/virology, CD4 Lymphocyte Count, Institutional repository, HIV Infections/blood/drug therapy/immunology/virology, HIV-2, HIV-1, RNA, Panton–Valentine leukocidin, business
Abstract

Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations, COHERE (HIV-1 alone) and ACHIeV2e (HIV-2 alone), were included, if they started first-line cART (without NNRTIs or fusion inhibitors) between 1997 and 2011. Patients without at least one CD4 cell count before start of cART, without a pretreatment pVL and with missing a priori-defined covariables were excluded. Evolution of CD4 cell count was studied using adjusted linear mixed models. Results: We included 185 HIV-2+ and 30321 HIV-1+ patients with median age of 46 years (IQR 36-52) and 37 years (IQR 31-44), respectively. Median observed pretreatment CD4 cell counts/mm(3) were 203 (95% CI 100-290) in HIV-2+ patients and 223 (95% CI 100-353) in HIV-1+ patients. Mean observed CD4 cell count changes from start of cART to 12months were + 105 (95% CI 77-134) in HIV-2+ patients and + 202 (95% CI 199-205) in HIV-1+ patients, an observed difference of 97 cells/mm(3) in 1 year. In adjusted analysis, the mean CD4 cell increase was overall 25 CD4 cells/mm(3)/year lower (95% CI 5-44; P=0.0127) in HIV-2+ patients compared with HIV-1+ patients. Conclusions: A poorer CD4 cell increase during first-line cART was observed in HIV-2+ patients, even after adjusting for pretreatment pVL and other potential confounders. Our results underline the need to identify more potent therapeutic regimens or strategies against HIV-2

Published
2017

108. 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

111. Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies

Author

Johnson, Leigh F., Mossong, Joel, Dorrington, Rob E., Schomaker, Michael, Hoffmann, Christopher J., Keiser, Olivia, Fox, Matthew P., Wood, Robin, Prozesky, Hans, Giddy, Janet, Garone, Daniela Belen, Cornell, Morna, Egger, Matthias, and Boulle, Andrew

Subjects
Antiviral agents -- Dosage and administration, Drug interactions -- Research, HIV patients -- Physiological aspects, Biological sciences
Abstract

Background: Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults. Methods and Findings: Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV- positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2-30.2) at age 20 y and 10.1 y (95% CI: 9.3-10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0-39.7) and 14.4 y (95% CI: 13.3-15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1-46.0) if her baseline CD4 count was [greater than or equal to] 200 cells/µl, compared to 29.5 y (95% CI: 26.2-33.0) if her baseline CD4 count was Conclusions: South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well., Introduction Estimates of life expectancies of HIV-infected individuals are important in providing information to patients about their long-term prognosis, in projecting the future costs of HIV-related care, and in forecasting [...]

Published
2013
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115. Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study

Author

Cornell, Morna, Schomaker, Michael, Garone, Daniela Belen, Giddy, Janet, Hoffmann, Christopher J., Lessells, Richard, Maskew, Mhairi, Prozesky, Hans, Wood, Robin, Johnson, Leigh F., Egger, Matthias, Boulle, Andrew, and Myer, Landon

Subjects
Antiviral agents -- Physiological aspects -- Health aspects, Biological sciences
Abstract

Background: Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART. Methods and Findings: Analyses included 46,201 ART-naive adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age- standardised HIV-negative population. Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow- up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p Conclusions: HIV-infected men have higher mortality on ART than women in South African programmes, but these differences are only partly explained by more advanced HIV disease at the time of ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. The observed differences in mortality on ART may be best explained by background differences in mortality between men and women in the South African population unrelated to the HIV/AIDS epidemic., Introduction South Africa has the largest antiretroviral therapy (ART) programme worldwide. The programme has undergone rapid expansion with nearly 1.64 million adults initiating ART since 2004 [1]. Given the unprecedented [...]

Published
2012
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116. Effect of Lopinavir and Nevirapine Concentrations on Viral Outcomes in Protease Inhibitor-experienced HIV-infected Children

Author

Moholisa, Retsilisitsoe R., primary, Schomaker, Michael, additional, Kuhn, Louise, additional, Castel, Sandra, additional, Wiesner, Lubbe, additional, Coovadia, Ashraf, additional, Strehlau, Renate, additional, Patel, Faeezah, additional, Pinillos, Francoise, additional, Abrams, Elaine J., additional, Maartens, Gary, additional, and McIlleron, Helen, additional

Published
2016
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117. Educational Note: Paradoxical collider effect in the analysis of non-communicable disease epidemiological data: a reproducible illustration and web application.

Author

Luque-Fernandez, Miguel Angel, Schomaker, Michael, Redondo-Sanchez, Daniel, Perez, Maria Jose Sanchez, Vaidya, Anand, Schnitzer, Mireille E, and Jose Sanchez Perez, Maria

Subjects
*WEB-based user interfaces, *NON-communicable diseases, *DIRECTED acyclic graphs, *SYSTOLIC blood pressure, *MEDICAL literature, *REGRESSION analysis
Abstract

Classical epidemiology has focused on the control of confounding, but it is only recently that epidemiologists have started to focus on the bias produced by colliders. A collider for a certain pair of variables (e.g. an outcome Y and an exposure A) is a third variable (C) that is caused by both. In a directed acyclic graph (DAG), a collider is the variable in the middle of an inverted fork (i.e. the variable C in A → C ← Y). Controlling for, or conditioning an analysis on a collider (i.e. through stratification or regression) can introduce a spurious association between its causes. This potentially explains many paradoxical findings in the medical literature, where established risk factors for a particular outcome appear protective. We use an example from non-communicable disease epidemiology to contextualize and explain the effect of conditioning on a collider. We generate a dataset with 1000 observations, and run Monte-Carlo simulations to estimate the effect of 24-h dietary sodium intake on systolic blood pressure, controlling for age, which acts as a confounder, and 24-h urinary protein excretion, which acts as a collider. We illustrate how adding a collider to a regression model introduces bias. Thus, to prevent paradoxical associations, epidemiologists estimating causal effects should be wary of conditioning on colliders. We provide R code in easy-to-read boxes throughout the manuscript, and a GitHub repository [https://github.com/migariane/ColliderApp] for the reader to reproduce our example. We also provide an educational web application allowing real-time interaction to visualize the paradoxical effect of conditioning on a collider [http://watzilei.com/shiny/collider/]. [ABSTRACT FROM AUTHOR]

Published
2019
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118. 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, primary, Leroy, Valeriane, additional, Wolfs, Tom, additional, Technau, Karl-Günter, additional, Renner, Lorna, additional, Judd, Ali, additional, Sawry, Shobna, additional, Amorissani-Folquet, Madeleine, additional, Noguera-Julian, Antoni, additional, Tanser, Frank, additional, Eboua, François, additional, Navarro, Maria Luisa, additional, Chimbetete, Cleophas, additional, Amani-Bosse, Clarisse, additional, Warszawski, Josiane, additional, Phiri, Sam, additional, N’Gbeche, Sylvie, additional, Cox, Vivian, additional, Koueta, Fla, additional, Giddy, Janet, additional, Sygnaté-Sy, Haby, additional, Raben, Dorthe, additional, Chêne, Geneviève, additional, and Davies, Mary-Ann, additional

Published
2016
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120. Mercury and neuromotor function among children in a rural town in Chile

Author

Ohlander, Johan, primary, Huber, Stella Maria, additional, Schomaker, Michael, additional, Heumann, Christian, additional, Schierl, Rudolf, additional, Michalke, Bernhard, additional, Jenni, Oskar G., additional, Caflisch, Jon, additional, Muñoz, Daniel Moraga, additional, von Ehrenstein, Ondine S., additional, and Radon, Katja, additional

Published
2016
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124. Growth and Mortality Outcomes for Different Antiretroviral Therapy Initiation Criteria in Children aged 1-5 Years

Author

Schomaker, Michael, primary, Davies, Mary-Ann, additional, Malateste, Karen, additional, Renner, Lorna, additional, Sawry, Shobna, additional, N’Gbeche, Sylvie, additional, Technau, Karl-Günter, additional, Eboua, François, additional, Tanser, Frank, additional, Sygnaté-Sy, Haby, additional, Phiri, Sam, additional, Amorissani-Folquet, Madeleine, additional, Cox, Vivian, additional, Koueta, Fla, additional, Chimbete, Cleophas, additional, Lawson-Evi, Annette, additional, Giddy, Janet, additional, Amani-Bosse, Clarisse, additional, Wood, Robin, additional, Egger, Matthias, additional, and Leroy, Valeriane, additional

Published
2015
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125. Tuberculosis and the risk of opportunistic infections and cancers in HIV-infected patients starting ART in Southern Africa

Author

Henostroza, German, Egger, Matthias, Reid, Stewart E., Boulle, Andrew, Wandeler, Gilles, Wood, Robin, Schomaker, Michael, Prozesky, Hans, Wellington, Maureen, Zwahlen, Marcel, and Fenner, Lukas

Subjects
parasitic diseases
Abstract

To investigate the incidence of selected opportunistic infections (OIs) and cancers and the role of a history of tuberculosis (TB) as a risk factor for developing these conditions in HIV-infected patients starting antiretroviral treatment (ART) in Southern Africa.

Published
2013
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126. The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis.

Author

null, null, Slogrove, Amy L., Schomaker, Michael, Davies, Mary-Ann, Williams, Paige, Balkan, Suna, Ben-Farhat, Jihane, Calles, Nancy, Chokephaibulkit, Kulkanya, Duff, Charlotte, Eboua, Tanoh François, Kekitiinwa-Rukyalekere, Adeodata, Maxwell, Nicola, Pinto, Jorge, IIISeage, George, Teasdale, Chloe A., Wanless, Sebastian, Warszawski, Josiane, Wools-Kaloustian, Kara, and Yotebieng, Marcel

Subjects
HIV, HIV infections, HIGHLY active antiretroviral therapy, SEXUALLY transmitted diseases, HIV status, HIV-positive persons, HIV infection transmission, PREVENTION of infectious disease transmission, ANTIRETROVIRAL agents, HIV infection epidemiology, INFECTIOUS disease transmission, COMPARATIVE studies, EPIDEMIOLOGY, INTERNATIONAL relations, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, RESEARCH, RESEARCH funding, WORLD health, EVALUATION research
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. [ABSTRACT FROM AUTHOR]

Published
2018
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129. Selektieren und Kombinieren von Modellen unter Berücksichtigung der Problematik fehlender Daten

Author

Schomaker, Michael and Schomaker, Michael

Abstract

In den letzten Jahren haben sich Modellmittelungsverfahren als Alternative zur Modellselektion etabliert. Anstatt sich auf ein einziges Siegermodell zu beschränken, werden hierbei mehrere konkurrierende Modelle betrachtet und ihre Parameterschätzer gewichtet miteinander kombiniert. Das Hauptaugenmerk liegt dabei meist auf der Konstruktion der Gewichte, wie auch der Optimalität der daraus resultierenden gewichteten Parameterschätzung. In der vorliegenden Arbeit werden verschiedene Konzepte frequentistischer Modellmittelung (Frequentist Model Averaging, FMA) erläutert und ihre Stärken und Schwächen gegenüber einer Vielzahl an traditionellen Modellselektionsmethoden herausgestellt. Schwerpunkt ist dabei die Konstruktion und Diskussion verschiedener Strategien zur Verwendung von FMA-Methoden unter Berücksichtigung der Problematik fehlender Daten. Hierfür werden zwei Kernkonzepte vorgeschlagen: Der erste Ansatz konstruiert Gewichte für einen FMA-Schätzer auf Basis eines für fehlende Daten adjustierten Kriteriums, welches der aktuellen Literatur aus dem Bereich der Modellselektion entstammt und das das im Kontext fehlender Werte bekannte Prinzip des inverse probability weighting verwendet; der zweite Ansatz ersetzt die fehlenden Werte durch Imputationen, um darauf aufbauend geeignete Schätzungen mit Hilfe bekannter Modellmittelungsansätze zu konstruieren. Zu diesem Zweck wird auch ein rekursiver Imputationsalgorithmus präsentiert, der die geläufige Idee einer Regressionsimputation unter Verwendung generalisierter additiver Modelle verallgemeinert. Die Arbeit zeigt die Eigenheiten, Stärken und Schwächen der vorgestellten Ansätze im Kontext von linearen und logistischen Regressionsanalysen anhand weitreichender Monte-Carlo-Simulationen auf und diskutiert am Beispiel der Faktorenanalyse mögliche Erweiterungen und Verallgemeinerungen der angeführten Schätzer für weitere multivariate, statistische Analysemethoden. Alle Verfahren werden an realen Datensätzen illustriert. Es zeigt sich, dass in vielen Situationen beide vorgestellten Konzepte einem Verwerfen der nicht-vollständigen Beobachtungen vorzuziehen sind, die Strategie einer Modellmittelung nach Imputation in der Regel bessere Resultate erzielt als die Verwendung eines FMA-Schätzers, der Gewichte auf Basis eines für fehlende Daten adjustierten Kriteriums verwendet, und insbesondere die technisch weniger aufwändigen Modellmittelungsverfahren zu besseren Schätzungen führen als diejenigen, die aus einer klassischen Modellselektion resultieren.

Published
2010

130. BackMatter.

Author

Heumann, Christian, Schomaker, Michael, and Shalabh

Published
2016

131. FrontMatter.

Author

Heumann, Christian, Schomaker, Michael, and Shalabh

Published
2016

132. Virologic Response in Children Treated With Abacavir-compared With Stavudine-based Antiretroviral Treatment

Author

Technau, Karl-Günter, primary, Schomaker, Michael, additional, Kuhn, Louise, additional, Moultrie, Harry, additional, Coovadia, Ashraf, additional, Eley, Brian, additional, Rabie, Helena, additional, Wood, Robin, additional, Cox, Vivian, additional, Vizcaya, Luisa Salazar, additional, Muchiri, Evans, additional, and Davies, Mary-Ann, additional

Published
2014
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134. Plasma Lopinavir Concentrations Predict Virological Failure in a Cohort of South African Children Initiating a Protease-Inhibitor-Based Regimen

Author

Moholisa, Retsilisitsoe R, primary, Schomaker, Michael, additional, Kuhn, Louise, additional, Meredith, Sandra, additional, Wiesner, Lubbe, additional, Coovadia, Ashraf, additional, Strehlau, Renate, additional, Martens, Leigh, additional, Abrams, Elaine J, additional, Maartens, Gary, additional, and McIlleron, Helen, additional

Published
2013
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137. Effectiveness of Patient Adherence Groups as a Model of Care for Stable Patients on Antiretroviral Therapy in Khayelitsha, Cape Town, South Africa

Author

Luque-Fernandez, Miguel Angel, primary, Van Cutsem, Gilles, additional, Goemaere, Eric, additional, Hilderbrand, Katherine, additional, Schomaker, Michael, additional, Mantangana, Nompumelelo, additional, Mathee, Shaheed, additional, Dubula, Vuyiseka, additional, Ford, Nathan, additional, Hernán, Miguel A., additional, and Boulle, Andrew, additional

Published
2013
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138. Growth and Mortality Outcomes for Different Antiretroviral Therapy Initiation Criteria in Children Ages 1-5 Years: A Causal Modeling Analysis.

Author

Schomaker, Michael, Davies, Mary-Ann, Malateste, Karen, Renner, Lorna, Sawry, Shobna, N'Gbeche, Sylvie, Technau, Karl-Günter, Eboua, François, Tanser, Frank, Sygnaté-Sy, Haby, Phiri, Sam, Amorissani-Folquet, Madeleine, Cox, Vivian, Koueta, Fla, Chimbete, Cleophas, Lawson-Evi, Annette, Giddy, Janet, Amani-Bosse, Clarisse, Wood, Robin, and Egger, Matthias

Subjects
ANTI-HIV agents, ATTRIBUTION (Social psychology), CHILD development, COMPARATIVE studies, DATABASES, HIV infections, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, RESEARCH, RESEARCH funding, TIME, EVALUATION research, HIGHLY active antiretroviral therapy, EARLY medical intervention, CD4 lymphocyte count
Abstract

Background: There is limited evidence regarding the optimal timing of initiating antiretroviral therapy (ART) in children. We conducted a causal modeling analysis in children ages 1-5 years from the International Epidemiologic Databases to Evaluate AIDS West/Southern-Africa collaboration to determine growth and mortality differences related to different CD4-based treatment initiation criteria, age groups, and regions.Methods: ART-naïve children of ages 12-59 months at enrollment with at least one visit before ART initiation and one follow-up visit were included. We estimated 3-year growth and cumulative mortality from the start of follow-up for different CD4 criteria using g-computation.Results: About one quarter of the 5,826 included children was from West Africa (24.6%).The median (first; third quartile) CD4% at the first visit was 16% (11%; 23%), the median weight-for-age z-scores and height-for-age z-scores were -1.5 (-2.7; -0.6) and -2.5 (-3.5; -1.5), respectively. Estimated cumulative mortality was higher overall, and growth was slower, when initiating ART at lower CD4 thresholds. After 3 years of follow-up, the estimated mortality difference between starting ART routinely irrespective of CD4 count and starting ART if either CD4 count <750 cells/mm³ or CD4% <25% was 0.2% (95% CI = -0.2%; 0.3%), and the difference in the mean height-for-age z-scores of those who survived was -0.02 (95% CI = -0.04; 0.01). Younger children ages 1-2 and children in West Africa had worse outcomes.Conclusions: Our results demonstrate that earlier treatment initiation yields overall better growth and mortality outcomes, although we could not show any differences in outcomes between immediate ART and delaying until CD4 count/% falls below 750/25%. [ABSTRACT FROM AUTHOR]

Published
2016
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140. Implementation of a comprehensive clinical risk management system in a university hospital

Author

Buchberger, Wolfgang, Schmied, Marten, Schomaker, Michael, del Rio, Anca, and Siebert, Uwe

Abstract

Adverse events during hospital treatment are common and can lead to serious harm. This study reports the implementation of a comprehensive clinical risk management system in a university hospital and assesses the impact of clinical risk management on patient harms.

Published
2023
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143. FrontMatter.

Author

Toutenburg, Helge, Schomaker, Michael, Wiβmann, Malte, and Heumann, Christian

Published
2009

144. Datenanalyse.

Author

Toutenburg, Helge, Schomaker, Michael, Wiβmann, Malte, and Heumann, Christian

Abstract

Copyright of Arbeitsbuch Zur Deskriptiven und Induktiven Statistik (9783540890355) is the property of Springer Nature / Books 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
2009
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145. Lineare Regression.

Author

Toutenburg, Helge, Schomaker, Michael, Wiβmann, Malte, and Heumann, Christian

Abstract

Copyright of Arbeitsbuch Zur Deskriptiven und Induktiven Statistik (9783540890355) is the property of Springer Nature / Books 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
2009
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146. Grundlagen.

Author

Toutenburg, Helge, Schomaker, Michael, Wiβmann, Malte, and Heumann, Christian

Abstract

Copyright of Arbeitsbuch Zur Deskriptiven und Induktiven Statistik (9783540890355) is the property of Springer Nature / Books 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
2009
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147. Häufigkeitsverteilungen.

Author

Toutenburg, Helge, Schomaker, Michael, Wiβmann, Malte, and Heumann, Christian

Abstract

Copyright of Arbeitsbuch Zur Deskriptiven und Induktiven Statistik (9783540890355) is the property of Springer Nature / Books 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
2009
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148. Analyse des Zusammenhangs zweier Merkmale.

Author

Toutenburg, Helge, Schomaker, Michael, Wiβmann, Malte, and Heumann, Christian

Abstract

Copyright of Arbeitsbuch Zur Deskriptiven und Induktiven Statistik (9783540890355) is the property of Springer Nature / Books 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
2009
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149. Maβzahlen für eindimensionale Merkmale.

Author

Toutenburg, Helge, Schomaker, Michael, Wiβmann, Malte, and Heumann, Christian

Abstract

Copyright of Arbeitsbuch Zur Deskriptiven und Induktiven Statistik (9783540890355) is the property of Springer Nature / Books 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
2009
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150. Kombinatorik.

Author

Toutenburg, Helge, Schomaker, Michael, Wiβmann, Malte, and Heumann, Christian

Abstract

Copyright of Arbeitsbuch Zur Deskriptiven und Induktiven Statistik (9783540890355) is the property of Springer Nature / Books 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
2009
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