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1. Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy

Author

A. Sarah Walker, Osamah Hamouda, Virginie Rondeau, Maria Dorrucci, Heiner C. Bucher, Maria Prins, Geneviève Chêne, Kholoud Porter, Caroline A. Sabin, Rodolphe Thiébaut, Benoît Marin, Dominique Costagliola, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de l'Information Médicale et de l'Évaluation [CHU Limoges] (SIME), CHU Limoges, Neuroépidémiologie Tropicale et Comparée (NETEC), Université de Limoges (UNILIM)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Basel Institute for Clinical Epidemiology, University Hospital Basel [Basel], Epidémiologie Clinique et Traitement de l'Infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Dipartimento di Malattie Infettive, Reparto di Epidemiologia, Istituto Superiore di Sanita [Rome], Department of Infectious Disease Epidemiology, Robert Koch Institute [Berlin] (RKI), Cluster Infectious Diseases, Amsterdam BioMed Cluster, Medical Research Council Clinical Trials Unit (MRC CTU), University College of London [London] (UCL), Research Department of Infection and Population Health [London], CASCADE has been funded through grants from the European Union BMH4-CT97-2550, QLK2-2000-01431, QLRT-2001-01708 and LSHP-CT-2006-018949., Istituto Superiore di Sanità (ISS), AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, and Infectious diseases

Subjects
Male, MESH: CD4 Lymphocyte Count, medicine.medical_treatment, CD4 cell count, Disease, MESH: Epidemiologic Methods, MESH: Antiretroviral Therapy, Highly Active, Hepatitis, Liver disease, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Neoplasms, Immunology and Allergy, MESH: Neoplasms, 030212 general & internal medicine, Causes of death, Immunodeficiency, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH: AIDS-Related Opportunistic Infections, Liver Diseases, Immunosuppression, Middle Aged, Human Immunodeficiency Virus/AIDS, Antiretroviral therapy, 3. Good health, Infectious Diseases, Cardiovascular Diseases, MESH: Young Adult, Female, Viral disease, Adult, medicine.medical_specialty, MESH: Immune Tolerance, MESH: Liver Diseases, Adolescent, Immunology, Article, Young Adult, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Immune Tolerance, medicine, Humans, Seroconversion, highly active, Aged, MESH: Acquired Immunodeficiency Syndrome, MESH: Adolescent, Acquired Immunodeficiency Syndrome, MESH: Humans, AIDS-Related Opportunistic Infections, 030306 microbiology, business.industry, MESH: Cardiovascular Diseases, MESH: Adult, medicine.disease, MESH: Male, CD4 Lymphocyte Count, Neoplasm, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Bacterial infection, Epidemiologic Methods, business, MESH: Female
Abstract

International audience; OBJECTIVE: To assess whether immunodeficiency is associated with the most frequent non-AIDS-defining causes of death in the era of combination antiretroviral therapy (cART). DESIGN: Observational multicentre cohorts. METHODS: Twenty-three cohorts of adults with estimated dates of human immunodeficiency virus (HIV) seroconversion were considered. Patients were seroconverters followed within the cART era. Measurements were latest CD4, nadir CD4 and time spent with CD4 cell count less than 350 cells/microl. Outcomes were specific causes of death using a standardized classification. RESULTS: Among 9858 patients (71 230 person-years follow-up), 597 died, 333 (55.7%) from non-AIDS-defining causes. Non-AIDS-defining infection, liver disease, non-AIDS-defining malignancy and cardiovascular disease accounted for 53% of non-AIDS deaths. For each 100 cells/microl increment in the latest CD4 cell count, we found a 64% (95% confidence interval 58-69%) reduction in risk of death from AIDS-defining causes and significant reductions in death from non-AIDS infections (32, 18-44%), end-stage liver disease (33, 18-46%) and non-AIDS malignancies (34, 21-45%). Non-AIDS-defining causes of death were also associated with nadir CD4 while being cART-naive or duration of exposure to immunosuppression. No relationship between risk of death from cardiovascular disease and CD4 cell count was found though there was a raised risk associated with elevated HIV RNA. CONCLUSION: In the cART era, the most frequent non-AIDS-defining causes of death are associated with immunodeficiency, only cardiovascular disease was associated with high viral replication. Avoiding profound and mild immunodeficiency, through earlier initiation of cART, may impact on morbidity and mortality of HIV-infected patients.

Published
2009
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2. Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy

Author

Marin, Benoît, Thiébaut, Rodolphe, Bucher, Heiner, Rondeau, Virginie, Costagliola, Dominique, Dorrucci, Maria, Hamouda, Osamah, Prins, Maria, Walker, A. Sarah, Porter, Kholoud, Sabin, Caroline, Chêne, Geneviève, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de l'Information Médicale et de l'Évaluation [CHU Limoges] (SIME), CHU Limoges, Neuroépidémiologie Tropicale et Comparée (NETEC), Université de Limoges (UNILIM)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Basel Institute for Clinical Epidemiology, University Hospital Basel [Basel], Epidémiologie Clinique et Traitement de l'Infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Dipartimento di Malattie Infettive, Reparto di Epidemiologia, Istituto Superiore di Sanita [Rome], Department of Infectious Disease Epidemiology, Robert Koch Institute [Berlin] (RKI), Cluster Infectious Diseases, Amsterdam BioMed Cluster, Medical Research Council Clinical Trials Unit (MRC CTU), University College of London [London] (UCL), Research Department of Infection and Population Health [London], and CASCADE has been funded through grants from the European Union BMH4-CT97-2550, QLK2-2000-01431, QLRT-2001-01708 and LSHP-CT-2006-018949.

Subjects
MESH: Immune Tolerance, MESH: Liver Diseases, MESH: CD4 Lymphocyte Count, CD4 cell count, MESH: Epidemiologic Methods, MESH: Antiretroviral Therapy, Highly Active, Hepatitis, MESH: Neoplasms, Causes of death, highly active, MESH: Acquired Immunodeficiency Syndrome, MESH: Adolescent, MESH: Aged, MESH: Humans, MESH: Middle Aged, MESH: AIDS-Related Opportunistic Infections, MESH: Cardiovascular Diseases, MESH: Adult, Human Immunodeficiency Virus/AIDS, MESH: Male, Antiretroviral therapy, MESH: Young Adult, Neoplasm, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Bacterial infection, MESH: Female
Abstract

International audience; OBJECTIVE: To assess whether immunodeficiency is associated with the most frequent non-AIDS-defining causes of death in the era of combination antiretroviral therapy (cART). DESIGN: Observational multicentre cohorts. METHODS: Twenty-three cohorts of adults with estimated dates of human immunodeficiency virus (HIV) seroconversion were considered. Patients were seroconverters followed within the cART era. Measurements were latest CD4, nadir CD4 and time spent with CD4 cell count less than 350 cells/microl. Outcomes were specific causes of death using a standardized classification. RESULTS: Among 9858 patients (71 230 person-years follow-up), 597 died, 333 (55.7%) from non-AIDS-defining causes. Non-AIDS-defining infection, liver disease, non-AIDS-defining malignancy and cardiovascular disease accounted for 53% of non-AIDS deaths. For each 100 cells/microl increment in the latest CD4 cell count, we found a 64% (95% confidence interval 58-69%) reduction in risk of death from AIDS-defining causes and significant reductions in death from non-AIDS infections (32, 18-44%), end-stage liver disease (33, 18-46%) and non-AIDS malignancies (34, 21-45%). Non-AIDS-defining causes of death were also associated with nadir CD4 while being cART-naive or duration of exposure to immunosuppression. No relationship between risk of death from cardiovascular disease and CD4 cell count was found though there was a raised risk associated with elevated HIV RNA. CONCLUSION: In the cART era, the most frequent non-AIDS-defining causes of death are associated with immunodeficiency, only cardiovascular disease was associated with high viral replication. Avoiding profound and mild immunodeficiency, through earlier initiation of cART, may impact on morbidity and mortality of HIV-infected patients.

Published
2009
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3. Temporal trends in postseroconversion CD4 cell count and HIV load: the Concerted Action on Seroconversion to AIDS and Death in Europe Collaboration, 1985-2002.

Author

Dorrucci M, Rezza G, Porter K, and Phillips A

Subjects
Adult, Disease Progression, Europe, Female, Humans, Linear Models, Male, Statistics as Topic, Survival Analysis, Time Factors, CD4 Lymphocyte Count trends, HIV Infections immunology, HIV Infections virology, Viral Load trends
Abstract

Objective: To determine whether early postseroconversion CD4 cell counts and human immunodeficiency virus (HIV) loads have changed over time., Methods: Our analysis was based on 22 cohorts of people with known dates of seroconversion from Europe, Australia, and Canada (Concerted Action on Seroconversion to AIDS and Death in Europe Collaboration). We focused on individuals seroconverting between 1985 and 2002 who had the first CD4 cell count (n=3687) or HIV load (n=1584) measured within 2 years of seroconversion and before antiretroviral use. Linear regression models were used to assess time trends in postseroconversion CD4 cell count and HIV load. Trends in time to key thresholds were also assessed, using survival analysis., Results: The overall median initial CD4 cell count was 570 cells/ microL (interquartile range [IQR], 413-780 cells/ microL). The median initial HIV load was 35,542 copies/mL (IQR, 7600-153,050 copies/mL; on log(10) scale, 3.9-5.2 log(10) copies/mL). The postseroconversion CD4 cell count changed by an average of -6.33 cells/ microL/year (95% confidence interval [CI], -8.47 to -4.20 cells/ microL/year; P<.001), whereas an increase was observed in log(10) HIV load (+0.044 log(10) copies/mL/year; 95% CI, +0.034 to +0.053 log(10) copies/mL/year). These trends remained after adjusting for potential confounders. The probability of progressing to a CD4 cell count of <500 cells/ microL by 24 months from seroconversion increased from 0.66 (95% CI, 0.63-0.69) for individuals who seroconverted before 1991 to 0.80 (95% CI, 0.75-0.84) for those who seroconverted during 1999-2002., Conclusion: These data suggest that, in Europe, there has been a trend of decrease in the early CD4 cell count and of increase in the early HIV load. Additional research will be necessary to determine whether similar trends exist in other geographical areas.

Published
2007
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