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13 results on '"Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings]"'

1. New signatures of poor CD4 cell recovery after suppressive antiretroviral therapy in HIV-1-infected individuals: involvement of miR-192, IL-6, sCD14 and miR-144

Author

Francisco J Hernández-Walias, María J Ruiz-de-León, Yolanda M. Pacheco, Francesc Vidal, Isaac Rosado-Sánchez, Esther Vázquez, Santiago Moreno, Julià Blanco, Manuel Leal, Alejandro Vallejo, Red Española de Investigación en SIDA, Comunidad de Madrid, Instituto de Salud Carlos III, Junta de Andalucía, [Hernández-Walias,F, Ruiz-de-León,MJ, Vázquez,E, Moreno,S, Vallejo,A] Laboratory of Immunovirology, Department of Infectious Diseases. Health Research Institute Ramon y Cajal (IRyCIS), University Hospital Ramon y Cajal, Madrid, Spain. [Rosado-Sánchez,I, Leal,M, Pacheco,YM] Biomedicine Institute of Seville (IBiS), University Hospital Virgen del Rocío, Seville, Spain. [Leal,M] Department of Internal Medicine and Infectious Diseases. Hospital Viamed, Santa Ángela de la Cruz, Seville, Spain. [Vidal,F] Infectious Diseases Unit and HIV/AIDS, Department of Internal Medicine, University Hospital Joan XXIII, IISPV, University Rovira i Virgili, Tarragona, Catalonia, Spain. [Blanco,J] AIDS Research Institute IrsiCaixa-HIVACAT, Research Institute of Health Sciences Germans Trias i Pujol, Badalona, Catalonia, Spain. [Blanco,J] University of Vic-University Central of Catalonia (UVIC-UCC), Vic, Catalonia, Spain., This work was supported in part by the Spanish AIDS Network 'Red de Investigación en Sida (RIS) 'RD16/0025/0001, Ayudas contratación de ayudantes de investigación y técnicos de laboratorio, Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid (PEJ15/bio/tl-0064 to MJRL and PEJ17/AI_BMD6683 to FHW), Health Institute Carlos III, PI18/01216, Junta de Andalucía, Consejería de Economía, Innovación, Ciencia y Empleo, Proyecto de Investigación de Excelencia CTS2593, and YMP was supported by the Consejería de Salud y Bienestar Social of Junta de Andalucía through the 'Nicolás Monardes' programme (C-0013-2017).

Subjects
0301 basic medicine, Oncology, CD4-Positive T-Lymphocytes, Male, Longitudinal study, Human immunodeficiency virus (HIV), Lipopolysaccharide Receptors, Cell recovery, lcsh:Medicine, HIV Infections, medicine.disease_cause, Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes [Medical Subject Headings], Exosomes, Diseases::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Retrospective Studies [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cell Count::Blood Cell Count::Leukocyte Count::Lymphocyte Count::CD4 Lymphocyte Count [Medical Subject Headings], Antiretroviral Therapy, Highly Active, Medicine, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-6 [Medical Subject Headings], lcsh:Science, MicroARNs, Multidisciplinary, biology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Therapy, Combination::Antiretroviral Therapy, Highly Active [Medical Subject Headings], Citocinas, Middle Aged, Antiretroviral therapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Sensitivity and Specificity::Predictive Value of Tests [Medical Subject Headings], Cd4 cell, Cytokines, Female, Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Cytoplasmic Vesicles::Transport Vesicles::Exosomes [Medical Subject Headings], VIH-1, Adult, medicine.medical_specialty, Phenomena and Processes::Chemical Phenomena::Physicochemical Phenomena::Solubility [Medical Subject Headings], Late Diagnoses, 030106 microbiology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Analysis of Variance::Multivariate Analysis [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Predictive markers, Article, 03 medical and health sciences, Text mining, Paired samples, Predictive Value of Tests, Internal medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies [Medical Subject Headings], Análisis multivariante, Humans, Interleukin 6, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Sensitivity and Specificity::ROC Curve [Medical Subject Headings], Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], business.industry, Interleukin-6, lcsh:R, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Delayed Diagnosis [Medical Subject Headings], MicroRNAs, 030104 developmental biology, Multivariate analysis, Check Tags::Female [Medical Subject Headings], ROC Curve, Solubility, Multivariate Analysis, biology.protein, HIV-1, lcsh:Q, business, Biomarkers
Abstract

Up to 40% of newly diagnosed cases of HIV-1 infection are late diagnoses, with a profound decrease in CD4 cell counts in many cases. One-third of these individuals do not achieve optimal CD4 cell recovery (OR) after suppressive antiretroviral treatment (ART). This retrospective/longitudinal study of poor recovery (PR) included 79 HIV-1-infected individuals with CD4 count, This work was supported in part by the Spanish AIDS Network “Red de Investigación en Sida (RIS)” RD16/0025/0001; Ayudas contratación de ayudantes de investigación y técnicos de laboratorio, Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid (PEJ15/bio/tl-0064 to MJRL and PEJ17/AI_BMD-6683 to FHW); Health Institute Carlos III, PI18/01216; Junta de Andalucía, Consejería de Economía, Innovación, Ciencia y Empleo, Proyecto de Investigación de Excelencia CTS2593; YMP was supported by the Consejería de Salud y Bienestar Social of Junta de Andalucía through the “Nicolás Monardes” programme (C-0013-2017).

Published
2020

2. Polyfunctional HIV-1 specific response by CD8+ T lymphocytes expressing high levels of CD300a

Author

Francisco Borrego, Miguel Genebat, Ane Orrantia, Ezequiel Ruiz-Mateos, Manuel Leal, Joana Vitallé, Leire Gamboa-Urquijo, Laura Tarancon-Diez, Iñigo Terrén, Olatz Zenarruzabeitia, [Vitallé,J, Terrén,I, Gamboa-Urquijo,L, Orrantia,A, Borrego,F, Zenarruzabeitia,O] Biocruces Bizkaia Health Research Institute, Immunopathology Group, Barakaldo, Spain. [Tarancón-Díez,L, Genebat,M, Leal,M, Ruiz-Mateos,E] Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, University of Seville, CSIC, Seville, Spain. [Tarancón-Díez,L] Laboratory of Molecular Immuno-Biology, Gregorio Marañón University Hospital, Health Research Institute, Madrid, Spain. [Leal,M] Internal Medicine Service, Santa Ángela de la Cruz Viamed Hospital, Sevilla, Spain. [Borrego,F] Ikerbasque, Basque Foundation for Science, Bilbao, Spain., This study was supported by a grant from 'Plan Estatal de I+ D+ I 2013–2016, ISCIII-Subdirección de Evaluación y Fomento de la Investigación-Fondo Europeo de Desarrollo Regional (FEDER) (Grant PI13/00889)' and Marie Curie Actions, Career Integration Grant, European Commission (Grant CIG 631674). Joana Vitallé and Iñigo Terrén are recipients of a predoctoral contract funded by the Department of Education, Basque Government (PRE_2017_2_0242 and PRE_2018_1_0032). Joana Vitallé and Iñigo Terrén are recipients of a fellowship from the Jesús de Gangoiti Barrera Foundation (FJGB15/008 and FJGB17/003). Laura Tarancón-Díez was supported by Instituto de Salud Carlos III, PFIS (FI00/00431). Olatz Zenarruzabeitia is recipient of a postdoctoral contract funded by 'Instituto de Salud Carlos III-Contratos Sara Borrell 2017 (CD17/0128)' and the European Social Fund (ESF)-The ESF invests in your future. Ezequiel Ruiz-Mateos is supported by Programa Nicolás Monardes, C0032-2017, Consejería de Salud y Bienestar Social, Junta de Andalucía. Francisco Borrego is an Ikerbasque Research Professor, Ikerbasque, Basque Foundation for Science., Instituto de Salud Carlos III, European Commission, Eusko Jaurlaritza, Fundación Jesús de Gangoiti Barrera, Junta de Andalucía, and Ikerbasque Basque Foundation for Science

Subjects
0301 basic medicine, Receptor expression, medicine.medical_treatment, T-Lymphocytes, lcsh:Medicine, HIV Infections, CD8-Positive T-Lymphocytes, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Cytotoxic T cell, Receptors, Immunologic, Receptor, lcsh:Science, Cells, Cultured, Multidisciplinary, medicine.diagnostic_test, CD300a receptor, Degranulation, virus diseases, Citocinas, Linfocitos T, 3. Good health, Cytokine, medicine.anatomical_structure, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents [Medical Subject Headings], 030220 oncology & carcinogenesis, Cytokines, Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [Medical Subject Headings], Cell biology, Anti-HIV Agents, T cell, Immunology, Biology, Article, Flow cytometry, 03 medical and health sciences, Antigens, CD, medicine, Humans, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides [Medical Subject Headings], Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Up-Regulation [Medical Subject Headings], lcsh:R, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intercellular Signaling Peptides and Proteins::Cytokines [Medical Subject Headings], Péptidos, 030104 developmental biology, Anatomy::Cells::Cells, Cultured [Medical Subject Headings], HIV-1, lcsh:Q, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CD [Medical Subject Headings], Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::T-Lymphocyte Subsets [Medical Subject Headings], Peptides, CD8, Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD8-Positive T-Lymphocytes [Medical Subject Headings]
Abstract

CD300a receptor is found on different CD8+ T cell subsets and its expression has been associated to a more cytotoxic molecular signature. CD300a has an important role in some viral infections and its expression levels are known to be modulated by human immunodeficiency virus (HIV)−1 infection on several cell types. The main objective of this work was to investigate CD300a expression and its regulation during HIV-1 specific CD8+ T cell responses. CD300a receptor expression was analysed by multiparametric flow cytometry on CD8+ T lymphocytes from HIV negative donors, naive HIV-1+ individuals and HIV-1+ subjects under suppressive combined antiretroviral therapy (cART). HIV-1 specific CD8+ T cell response was studied by stimulating cells with HIV-1 derived peptides or with a Gag HIV-1 peptide. Our results showed that HIV-1 specific CD8+ T cells expressing higher levels of CD300a were more polyfunctional showing an increased degranulation and cytokine production. Moreover, we observed an up-regulation of CD300a expression after Gag HIV-1 peptide stimulation. Finally, our results demonstrated an inverse correlation between CD300a expression on CD8+ T lymphocytes and HIV disease progression markers. In conclusion, CD300a expression is associated to a better and more polyfunctional HIV-1 specific CD8+ T cell response., This study was supported by a grant from “Plan Estatal de I+ D+ I 2013–2016, ISCIII-Subdirección de Evaluación y Fomento de la Investigación-Fondo Europeo de Desarrollo Regional (FEDER) (Grant PI13/00889)” and Marie Curie Actions, Career Integration Grant, European Commission (Grant CIG 631674). Joana Vitallé and Iñigo Terrén are recipients of a predoctoral contract funded by the Department of Education, Basque Government (PRE_2017_2_0242 and PRE_2018_1_0032). Joana Vitallé and Iñigo Terrén are recipients of a fellowship from the Jesús de Gangoiti Barrera Foundation (FJGB15/008 and FJGB17/003). Laura Tarancón-Díez was supported by Instituto de Salud Carlos III, PFIS (FI00/00431). Olatz Zenarruzabeitia is recipient of a postdoctoral contract funded by “Instituto de Salud Carlos III-Contratos Sara Borrell 2017 (CD17/0128)” and the European Social Fund (ESF)-The ESF invests in your future. Ezequiel Ruiz-Mateos is supported by Programa Nicolás Monardes, C0032-2017, Consejería de Salud y Bienestar Social, Junta de Andalucía. Francisco Borrego is an Ikerbasque Research Professor, Ikerbasque, Basque Foundation for Science.

Published
2020

3. Risk, Diagnostic and Predictor Factors for Classical Hodgkin Lymphoma in HIV-1-Infected Individuals: Role of Plasma Exosome-Derived miR-20a and miR-21

Author

Francisco Tejerina-Picado, Ana Moreno, José L. Casado, María José Galindo, Asunción Hernando, Fernando Dronda, María J Pérez-Elías, Víctor Asensi, Manuel Leal, Yolanda M. Pacheco, José Hermida, Alejandro Vallejo, Esther Vázquez, Francisco J Hernández-Walias, José M Rodríguez-Fernández, Carmen Quereda, Santiago Moreno, [Hernández-Walias,FJ, Vázquez,E, Pérez-Elías,MJ, Dronda,F, Casado,JL, Moreno,A, Hermida,JM, Quereda,C, Moreno,S, Vallejo,A] Laboratory of Immunovirology, Infectious Diseases Department, Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, Madrid, Spain. [Pacheco,Y, Leal,M] Biomedicine Institute of Seville (IBiS), University Hospital Virgen del Rocío, Seville, Spain. [Rodríguez-Fernández,JM] Department of Internal Medicine, Gómez Ulla Central Hospital, Madrid, Spain. [Hernando,A] Department of Medicine, 12 de Octubre University Hospital, Universidad European University of Madrid, Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain. [Tejerina-Picado,F] Gregorio Marañón University General Hospital, Madrid, Spain. [Asensi,V] Infectious Diseases Department, Central University Hospital of Asturias, University Medical School, Oviedo, Spain. [Asensi,V] Group of Translational Research in Infectious Diseases, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain. [Galindo,MJ] Clinic University Hospital of Valencia, Valencia, Spain. [Leal,M] Department of Internal Medicine and Infectious Diseases, Viamed Hospital, Santa Ángela de la Cruz, Seville, Spain., and Instituto de Salud Carlos III, Spanish Health Ministry, with Grant numbers PI10-1077 and PI15-657. The HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by Instituto de Salud Carlos III, Spanish Healt Ministry (Grant nº D06/0006/0035, RD12/0017/0037 and RD16/0025/0019) as part of the Plan Nacional R+D+I and cofinanced by ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). This study (RIS-EPICLIN-03/2010) would not have been possible without the collaboration of all the patients, medical and nursery staff and data managers who have taken part in the project. The RIS Cohort (CoRIS) is funded by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en SIDA (RIS C03/173, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional R+D+I and cofinanced by ISCIII-Subdirección General de Evaluacion y el Fondo Europeo de Desarrollo Regional (FEDER).

Subjects
Exosome miRs, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], medicine.medical_treatment, lcsh:Medicine, Likelihood ratios in diagnostic testing, Gastroenterology, Exosomas, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Tratamiento médico, 0302 clinical medicine, immune system diseases, Information Science::Information Science::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], hemic and lymphatic diseases, Anatomy::Cells::Antibody-Producing Cells::B-Lymphocytes [Medical Subject Headings], cell phenotyping, polycyclic compounds, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-6 [Medical Subject Headings], Tecnología médica, MicroARNs, 0303 health sciences, education.field_of_study, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Incidence (epidemiology), Diseases::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Hodgkin Disease [Medical Subject Headings], food and beverages, General Medicine, Cáncer, 030220 oncology & carcinogenesis, Enfermedad de Hodgkin, Biomarker (medicine), Anatomy::Hemic and Immune Systems::Blood::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Killer Cells, Natural [Medical Subject Headings], Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Cytoplasmic Vesicles::Transport Vesicles::Exosomes [Medical Subject Headings], exosome miRs, medicine.medical_specialty, Sida, Population, macromolecular substances, Exosome, Article, 03 medical and health sciences, Internal medicine, VIH (Virus), Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunologic Tests::Immunophenotyping [Medical Subject Headings], medicine, Classical Hodgkin lymphoma, Persons::Persons::Age Groups::Adult [Medical Subject Headings], education, 030304 developmental biology, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Chemotherapy, Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], business.industry, lcsh:R, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Area Under Curve [Medical Subject Headings], Cancer, biomarkers, Andalucía, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Receptors, Tumor Necrosis Factor, Type I [Medical Subject Headings], medicine.disease, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [Medical Subject Headings], Biomarcadores, Inmunofenotipificación, HIV-1, Cell phenotyping, business, Biomarkers, Hodgkin lymphoma
Abstract

The incidence of classical Hodgkin lymphoma (cHL) in the HIV-1 setting has increased 5&ndash, 25-fold compared to that observed in the general population. This study aimed to determine whether selected micro RNAs (miRs) and other soluble biomarkers and cellular subsets are dysregulated in cHL and could be used as biomarkers. This was a retrospective and longitudinal matched case-control study of 111 Caucasian, HIV-1-infected adult individuals, including 37 individuals with cHL and 74 with no type of cancer. Immunovirological data, plasma exosome-derived miR-16, miR-20a, miR-21, miR-221, miR-223, miR-106a, miR-185, miR-23, miR-30d, miR-222, miR-146a and miR-324, plasma IL-6, sCD14, sCD27, sCD30, sIL-2R, TNFR1, and cell phenotyping of T and B lymphocytes and natural killer (NK) cells were analyzed. Before cHL diagnosis, miR-20a, miR-21, and sCD30 were higher in cHL (p = 0.008, p = 0.009 and p = 0.042, respectively), while miR-16 was down-regulated (p = 0.040). miR-20a and miR-21 were independently associated with cHL (p = 0.049 and p = 0.035, respectively). The combination of miR-20a and miR-21 showed a good AUC value of 0.832 with a moderate likelihood ratio positive (LR+) value of 5.6 and a slight likelihood ratio negative (LR&minus, ) value of 0.23. At cHL diagnosis, miR-20a, miR-21 and miR-324 were overexpressed in cHL (p = 0.005, p = 0.024, and p = 0.001, respectively), while miR-223, miR-16, miR-185 and miR-106a were down regulated (p = 0.042, p = 0.007, p = 0.006, and p = 0.002, respectively). In addition, sCD14, sCD27, sCD30 and IL2R levels were higher in these individuals (p = 0.038, p = 0.010, p = 0.030, p = 0.006, respectively). miR-20a was independently associated with cHL (p = 0.011). The diagnostic value of miR-20a showed good AUC value of 0.754 (p = 0.074) with a slight LR+ value of 2 and a slight LR&minus, of 0.25. After chemotherapy, miR-20a was higher in those individuals who had an adverse outcome (p &lt, 0.001), while sCD14 and sCD30 were higher (p &lt, 0.001). A specific signature of miRs and cytokines associated with a subsequent cHL diagnosis was found in this study, especially miR-20a and miR-21. Also, another biomarker signature was found at cHL diagnosis, with a relevant discriminant disease value for miR-20a. Of note, miR-20a expression was higher in those individuals who had an adverse clinical outcome after chemotherapy.

Published
2020

4. Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure

Author

Cecilio López-Galíndez, Rebeca S. de Pablo-Bernal, Carmen Rodríguez, Isabel Olivares, Ezequiel Ruiz-Mateos, Maria Pernas, Mar Vera, Alberto Merino-Mansilla, Ramon Lorenzo-Redondo, Victor Sanchez-Merino, Maria Cristina O. Salgado, Cristina Gálvez, Concepción Casado, Javier Martinez-Picado, Laura Tarancon-Diez, Jorge del Romero, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Red Española de Investigación en SIDA, European Commission, Junta de Andalucía, Grifols, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Red de Investigación Cooperativa en Investigación en Sida (España), Regional Government of Andalusia (España), [Casado,C, Pernas,M, Olivares,I, Lopez-Galindez,C] Virología Molecular, Laboratorio de Referencia e Investigación en Retrovirus, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. [Galvez,C, Salgado,M, Martinez-Picado,J] AIDS Research Institute IrsiCaixa, Badalona, Spain. [Galvez,C] Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain. [Tarancon-Diez,L, De Pablo-Bernal,R, Ruiz-Mateos,E] Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain. [Rodriguez,C, Vera,M, Del Romero,J] Centro Sanitario Sandoval, Hospital Clínico San Carlos. IdISSC, Madrid, Spain. [Sanchez-Merino,V, Merino-Mansilla,A] AIDS Immunopathology Unit. Laboratorio de Referencia e Investigación en Retrovirus. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. [Lorenzo-Redondo,R] Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. [Martinez-Picado,J] University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain. [Martinez-Picado,J] Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain., Work in Centro Nacional de Microbiologia (ISCIII) was supported by grants SAF (2016–77894-R) from Ministerio de Economia y Competitividad (MINECO) (Spain) and Fondo de Investigación Sanitaria(FIS)-Instituto de Salud CarlosIII, grant FIS (PI 13/02269, ISCIII) and in part by the RIS-RETIC grants RD12/0017/0028 and RD16CIII/0002/0005 funded by the ISCIII-FEDER. MP has a contract of RIS-RETICRD16CIII/0002/0005. Tis work was supported by grants from the MINECO, FIS-Instituto de Salud CarlosIII, Fondos Europeos para el Desarrollo Regional, FEDER, grant numbers PI16/00684, PI19/01127, CPII014/00025 to ER-M. and FI14/00431 to LT-D., the Gilead Fellowship Program (grant numbers GLD17/00299), and the Red de Investigación en Sida (grant number RD16/0025/0020). ER-M. is supported by Consejería de Salud y BienestarSocial of Junta de Andalucía through the Nicolás Monardes Program (C-0032/17). Research in VS-M group was supported by Fondo de Investigación Sanitaria (FIS)-Instituto de Salud CarlosIII, grant FIS (PI 17CIII/00049). Grifols partially supported work in the AIDS Research Institute IrsiCaixa.

Subjects
0301 basic medicine, Male, ADN, Remission, Spontaneous, Diseases, HIV Infections, Pathogenesis, Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes [Medical Subject Headings], Virus Replication, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, Microbial::Genes, Viral::Genes, env [Medical Subject Headings], Viral load, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Biological [Medical Subject Headings], Multidisciplinary, Molecular medicine, Middle Aged, Viral Load, Virus, Viral evolution, Viruses, Spontaneous cure, Disease Progression, Medicine, Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [Medical Subject Headings], Female, medicine.symptom, VIH-1, Evolution, Science, 030106 microbiology, Check Tags::Male [Medical Subject Headings], Inflammation, Models, Biological, Article, HIV Long-Term Survivors, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Microbiological Techniques::Viral Load [Medical Subject Headings], 03 medical and health sciences, Immune system, Elite controllers, HIV, Progresión de la enfermedad, medicine, Humans, Allele, Disease progression, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Progression [Medical Subject Headings], Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], Host Microbial Interactions, business.industry, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], DNA, Phenomena and Processes::Immune System Phenomena::Immunity [Medical Subject Headings], Persons::Persons::Patients::Survivors::HIV Long-Term Survivors [Medical Subject Headings], Carga viral, Phenomena and Processes::Microbiological Phenomena::Microbiological Processes::Virus Physiological Processes::Virus Replication [Medical Subject Headings], 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Viral replication, Immunology, HIV-1, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Progression::Remission, Spontaneous [Medical Subject Headings], VIH no-progresivos, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA [Medical Subject Headings], business, Biomarkers
Abstract

Elite controllers (EC) represent a small subset of HIV-1-infected people that spontaneously control viral replication. However, natural virological suppression and absence of immune dysfunction are not always long-term sustained. We define exceptional EC (EEC) as HIV-1 subjects who maintain the EC characteristics without disease progression for more than 25 years. We analyzed three EEC, diagnosed between 1988 and 1992, who never showed signs of clinical disease progression in absence of any antiretroviral treatment. A comprehensive clinical, virological, and immunological study was performed. The individuals simultaneously exhibited ≥3 described host protective alleles, low levels of total HIV-1 DNA (0.50). Inflammation levels of EEC were similar to HIV-1 negative donors. Remarkably, they showed an exceptional lack of viral evolution and 8-fold lower genetic diversity (, Work in Centro Nacional de Microbiologia (ISCIII) was supported by grants SAF (2016–77894-R) from Ministerio de Economia y Competitividad (MINECO) (Spain) and Fondo de Investigación Sanitaria (FIS)-Instituto de Salud CarlosIII, grant FIS (PI 13/02269, ISCIII) and in part by the RIS-RETIC grants RD12/0017/0028 and RD16CIII/0002/0005 funded by the ISCIII-FEDER. MP has a contract of RIS-RETIC RD16CIII/0002/0005. This work was supported by grants from the MINECO, FIS-Instituto de Salud CarlosIII, Fondos Europeos para el Desarrollo Regional, FEDER, grant numbers PI16/00684, PI19/01127, CPII014/00025 to ER-M. and FI14/00431 to LT-D.; the Gilead Fellowship Program (grant numbers GLD17/00299); the Red de Investigación en Sida (grant number RD16/0025/0020). ER-M. is supported by Consejería de Salud y Bienestar Social of Junta de Andalucía through the Nicolás Monardes Program (C-0032/17). Research in VS-M group was supported by Fondo de Investigación Sanitaria (FIS)-Instituto de Salud Carlos III, grant FIS (PI 17CIII/00049). Grifols partially supported work in the AIDS Research Institute IrsiCaixa.

Published
2020

5. Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe

Author

Judd, A, Lodwick, R, Noguera‐Julian, A, Gibb, DM, Butler, K, Costagliola, D, Sabin, C, van Sighem, A, Ledergerber, B, Torti, C, Mocroft, A, Podzamczer, D, Dorrucci, M, De Wit, S, Obel, N, Dabis, F, Cozzi‐Lepri, A, García, F, Brockmeyer, NH, Warszawski, J, Gonzalez‐Tome, MI, Mussini, C, Touloumi, G, Zangerle, R, Ghosn, J, Castagna, A, Fätkenheuer, G, Stephan, C, Meyer, L, Campbell, MA, Chene, G, Phillips, A, Mary Krause, Murielle, Leport, Catherine, Wittkop, Linda, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Bucher, Heiner, Gibb, Diana, Amo, Julia Del, Thorne, Claire, Kirk, Ole, Pérez‐Hoyos, Santiago, Hamouda, Osamah, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Antinori, Andrea, Monforte, Antonella d'Arminio, Prieto, Luis, Rojo, Pablo, Soriano‐Arandes, Antoni, Battegay, Manuel, Kouyos, Roger, Tookey, Pat, Casabona, Jordi, Miró, Jose M., Konopnick, Deborah, Goetghebuer, Tessa, Sönnerborg, Anders, Teira, Ramon, Garrido, Myriam, Haerry, David, Raben, Dorthe, Chêne, Geneviève, Barger, Diana, Schwimmer, Christine, Termote, Monique, Frederiksen, Casper M., Friis‐Møller, Nina, Kjaer, Jesper, Salbøl Brandt, Rikke, Berenguer, Juan, Bohlius, Julia, Bouteloup, Vincent, Davies, Mary‐Anne, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Grabar, Sophie, Lambotte, Olivier, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Puoti, Massimo, Schomaker, Michael, Smit, Colette, Sterne, Jonathan, Thiebaut, Rodolphe, van der Valk, Marc, Wyss, Natasha, The Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord, AII - Infectious diseases, APH - Aging & Later Life, Global Health, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, APH - Global Health, Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord., [Judd,A, Gibb,DM] MRC Clinical Trials Unit, University College London, London, UK. [ Lodwick,R, Sabin,C, Mocroft,A, Cozzi-Lepri,A, Phillips,A] Department of Infection and Population Health, University College London, London, UK. [Noguera-Julian,A] Institut de Recerca Pedi atrica Hospital Sant Joan de Deu, Barcelona, Spain. Departament de Pediatria, Universitat de Barcelona, Barcelona, Spain. CIBER de Epidemiologıa y Salud Publica Ciberesp, Barcelona, Spain. [Butler,K] Department of Infectious Diseases and Immunology, Our Lady’s Children’s Hospital, Crumlin, Dublin, Ireland. [Costagliola,D] INSERM, UPMC Univ Paris 06, Institut Pierre Louis d’epidemiologie et de Sante Publique (IPLESP UMRS 1136), Sorbonne Universites, Paris, France. [van Sighem,A] Stichting HIV Monitoring, Amsterdam, The Netherlands. [Ledergerber,B] Division of Infectious Diseases and Hospital Epidemiology, University of Zurich, Zurich, Switzerland. [Torti,C] Unit of Infectious and Tropical Diseases, Department of Medical and Surgical Sciences, University 'Magna Graecia', Catanzaro, Italy. [Podzamczer,D[ HUV and STD Unit, Infectious Diseases Service, Hospital Universitari de Bellvitge. L’Hospitalet, Barcelona, Spain. [Dorrucci,M] Istituto Superiore di Sanit a, Rome, Italy. [De Wit,S] Departement of Infectious Diseases, Centre Hospitalier Saint-Pierre, Universite Libre de Bruxelles, Brussels, Belgium. [Obel,N] Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. [Dabis,F, Chene,D] NSERM U1219 – Centre Inserm Bordeaux Population Health, Universite de Bordeaux, Bordeaux, France. ISPED, Centre INSERM U1219-Bordeaux Population Health, Universite de Bordeaux, Bordeaux, France. [Garcia,F] Clinical Microbiology Department, Complejo Hospitalario Universitario Granada, Instituto de Investigacion Biosanitaria ibs.Granada, Granada, Spain. [Brockmeyer,NH] Department of Dermatology, Venerology and Allergology, Center for Sexual Health and Medicine, St. Josef Hospital, Ruhr-Universität Bochum, Bochum, Germany. [Warszawski,J] INSERM CESP U1018, AP-HP Public Health Department, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre Paris, France. [Gonzalez-Tome,MI] HIV and Paeds Infectious Diseases Department, Hospital 12 de Octubre, Madrid, Spain. [Mussini,C] Infectious Diseases Clinics, University Hospital, Modena, Italy. [Touloumi,G] Department Hygiene, Epidemiology & Medical Statistics, Medical School, National & Kapodistrian University of Athens, Athens, Greece. [Zangerle,R] Medical University Innsbruck, Innsbruck, Austria. [Ghosn,J] EA 7327, Faculté de Médecine site Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. APHP, Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Hôpitaux Universitaires Paris Centre site Hôtel Dieu, Paris, France. [Castagna,A] San Raffaele Scientific Institute, Vita-SaLute University, Milan, Italy. [Fätkenheuer,G] Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany. [Stephan,C] Second Medical Department, Infectious Diseases Unit, Goethe-University Hospital, Frankfurt, Germany. [Meyer,L] NSERM CESP U1018, Université Paris-Sud, Université Paris-Saclay, Paris, France. AP-HP Public Health Department, Le Kremlin-Bicêtre, Paris, France. [Campbell,MA] Centre for Health and Infectious Disease Research, University of Copenhagen, Copenhagen, Denmark. [Chene,G]. CHU de Bordeaux, Pole de sante publique, Service d'information medicale, Bordeaux, France., Financial disclosure: The PLATO II project is funded by the UK Medical Research Council (award G0700832). The COHERE study group has received unrestricted funding from: Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS), France, the HIV Monitoring Foundation, The Netherlands, and the Augustinus Foundation, Denmark. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement no 260694. The group has also received project-specific funding from the UK Medical Research Council and the Swiss Bridge Foundation., Judd, A, Lodwick, R, Noguera-Julian, A, Gibb, D, Butler, K, Costagliola, D, Sabin, C, van Sighem, A, Ledergerber, B, Torti, C, Mocroft, A, Podzamczer, D, Dorrucci, M, De Wit, S, Obel, N, Dabis, F, Cozzi-Lepri, A, García, F, Brockmeyer, N, Warszawski, J, Gonzalez-Tome, M, Mussini, C, Touloumi, G, Zangerle, R, Ghosn, J, Castagna, A, Fätkenheuer, G, Stephan, C, Meyer, L, Campbell, M, Chene, G, Phillips, A, Puoti, M, Goethe-Universität Frankfurt am Main, Sexualité et soins (Genre, Sexualité, Santé) (CESP - INSERM U1018 - Equipe 7), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Copenhagen = Københavns Universitet (UCPH), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, University College of London [London] (UCL), Universitat Autònoma de Barcelona (UAB), Hospital Sant Joan de Déu [Barcelona], CIBER de Epidemiología y Salud Pública (CIBERESP), Our Lady's Children's Hospital Crumlin (OLCHC), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), University hospital of Zurich [Zurich], Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Istituto Superiore di Sanita [Rome], Université libre de Bruxelles (ULB), Copenhagen University Hospital, Universidad de Granada = University of Granada (UGR), Ruhr-Universität Bochum [Bochum], Hospital Universitario 12 de Octubre [Madrid], Azienda Ospedaleria Universitaria di Modena, National and Kapodistrian University of Athens (NKUA), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), University Hospital of Cologne [Cologne], HAL-SU, Gestionnaire, and The Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in, Eurocoord

Subjects
Male, HIV Infections, Pharmacologie, Santé publique, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Sexual Behavior::Sexuality::Heterosexuality [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Pharmacology (medical), Inhibidores de proteasas, Young adult, Europe, perinatal HIV infection, virological failure, young people, Adolescent, Adult, Anti-Retroviral Agents, Child, Child, Preschool, Cohort Studies, Female, Humans, Infant, Time Factors, Treatment Failure, Young Adult, Drug Resistance, Viral, Population Groups, Pathologie maladies infectieuses, ComputingMilieux_MISCELLANEOUS, Adolescente, ADN polimerasa dirigida por ADN, Original Research, Health Policy, Enfermedades transmisibles, 3. Good health, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents [Medical Subject Headings], G0700832, Young people, Viral load, Human, Factores de riesgo, medicine.medical_specialty, 030106 microbiology, HIV Infections/drug therapy, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Reverse Transcriptase Inhibitors [Medical Subject Headings], 03 medical and health sciences, Virological failure, Recién nacido, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA [Medical Subject Headings], Heterosexualidad, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Bacterial Infections and Mycoses::Infection::Communicable Diseases [Medical Subject Headings], Perinatal HIV infection, RCUK, medicine.disease, Infecciones por VIH, Persons::Persons::Age Groups::Infant::Infant, Newborn [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Viral Load [Medical Subject Headings], Observational study, Geographical Locations::Geographic Locations::Europe [Medical Subject Headings], 0301 basic medicine, Pediatrics, Science et gestion hospitalières, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Nucleotidyltransferases::DNA Nucleotidyltransferases::DNA-Directed DNA Polymerase [Medical Subject Headings], Diseases::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections [Medical Subject Headings], Anti-Retroviral Agents/therapeutic use, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Confidence Intervals [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Interquartile range, Epidemiology, HIV Infection, 030212 general & internal medicine, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Adulto, MRC, Infectious Diseases, Niño, Europa, VIH-1, Population Group, Time Factor, Persons::Persons::Age Groups::Adolescent [Medical Subject Headings], Acquired immunodeficiency syndrome (AIDS), medicine, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors [Medical Subject Headings], Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections::Acquired Immunodeficiency Syndrome [Medical Subject Headings], Persons::Persons::Age Groups::Child [Medical Subject Headings], ddc:610, Intervalos de confianza, Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], business.industry, Inhibidores de la transcriptasa inversa, Confidence interval, Carga viral, Fármacos anti-VIH, Anti-Retroviral Agent, Cohort Studie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Objectives: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. Methods: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15–29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI. Results: The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4–111) vs. 8 (IQR 2–38) weeks, respectively], and highest in perinatally infected participants aged 10–14 years [49 (IQR 9–267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0−12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9−5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10–14 years when starting ART (27.7%; 95% CI 13.2−42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10–14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4. Conclusions: The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development., 0, SCOPUS: ar.j, FLWOA, info:eu-repo/semantics/published

Published
2017

6. Abacavir/Lamivudine plus Rilpivirine Is an Effective and Safe Strategy for HIV-1 Suppressed Patients: 48 Week Results of the SIMRIKI Retrospective Study

Author

Troya, Jesús, Ryan, Pablo, Ribera, Esteban, Podzamczer, Daniel, Hontañón, Victor, Terrón, Jose Alberto, Boix, Vicente, Moreno, Santiago, Barrufet, Pilar, Castaño, Manuel, Carrero, Ana, Galindo, María José, Suárez-Lozano, Ignacio, Knobel, Hernando, Raffo, Miguel, Solís, Javier, Yllescas, María, Esteban, Herminia, González-García, Juan, Berenguer, Juan, Imaz, Arkaitz, GESIDA-8314 Study Group, GESIDA-8314 Study Group, [Troya,J, Solís,J] Hospital Universitario Infanta Leonor, Madrid, Spain. [Ribera,E] Hospital Universitario Vall d’Hebrón, Barcelona, Spain. [Podzamczer,D, Imaz,A] ] Hospital Universitario de Bellvitge, Barcelona, Spain. [Hontañón,V, González-García,J] Hospital Universitario La Paz/IdiPAZ, Madrid, Spain. [Terrón,JA] Hospital Jerez de la Frontera, Jerez de la Frontera, Spain. [Boix,V] Hospital General Universitario de Alicante, Alicante, Spain. [Moreno,S] Hospital Universitario Ramón y Cajal, Madrid, Spain. [Barrufet,P] Hospital de Mataró, Mataró, Spain. [Castaño,M, Berenguer,J] Hospital Regional Universitario de Málaga, Málaga, Spain. [Carrero,A] Hospital Universitario Gregorio Marañón, Madrid, Spain. [Galindo,MJ] Hospital Clínico de Valencia, Valencia, Spain. [Suárez-Lozano,I, Raffo,M] Hospital Universitario Infanta Elena, Huelva, Spain. [Knobel,H] Hospital del Mar, Barcelona, Spain. [Yllescas,M, Esteban,H] Fundación SEIMCGESIDA, Madrid, Spain., and The study was supported by ViiV Healthcare and SEIMC-GESIDA Foundation (grant number Gesida-8314).

Subjects
Male, HIV Infections, Pathology and Laboratory Medicine, Gastroenterology, Biochemistry, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Retrospective Studies [Medical Subject Headings], Immunodeficiency Viruses, Abacavir, Animal Cells, Análisis de intención de tratar, Lymphocytes, Masculino, lcsh:Science, Depression, Lamivudine, virus diseases, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidine Nucleosides::Cytidine::Deoxycytidine::Zalcitabine::Lamivudine [Medical Subject Headings], Antiretrovirals, Lipids, Humanos, Drug Combinations, Cholesterol, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Controlled Clinical Trials as Topic::Randomized Controlled Trials as Topic::Intention to Treat Analysis [Medical Subject Headings], Medical Microbiology, Viral Pathogens, Lípidos, Drug Therapy, Combination, Cellular Types, medicine.medical_specialty, Immune Cells, 030106 microbiology, Immunology, Check Tags::Male [Medical Subject Headings], Chemicals and Drugs::Lipids [Medical Subject Headings], Microbiology, Limfòcits, Drug Administration Schedule, 03 medical and health sciences, Estudios retrospectivos, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA [Medical Subject Headings], VIH (Virus) -- Tractament, Humans, Microbial Pathogens, Retrospective Studies, Pharmacology, Blood Cells, lcsh:R, Rilpivirine, Organisms, Kidney metabolism, Recuento de Linfocito CD4, Abacavir/Lamivudine, Infecciones por Vih, Dideoxynucleosides, Regimen, chemistry, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Oxazines::Benzoxazines [Medical Subject Headings], HIV-1, lcsh:Q, 0301 basic medicine, RNA viruses, lcsh:Medicine, Kidney, chemistry.chemical_compound, Efectos colaterales y reacciones adversas relacionados con medicamentos, White Blood Cells, Medicine and Health Sciences, Chemicals and Drugs::Pharmaceutical Preparations::Drug Combinations [Medical Subject Headings], Drug Interactions, 030212 general & internal medicine, Tasa de filtración glomerular, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Urological::Kidney Function Tests::Glomerular Filtration Rate [Medical Subject Headings], Multidisciplinary, Antimicrobials, Drugs, HIV diagnosis and management, Middle Aged, Antivirals, ARN, Treatment Outcome, Tolerability, Liver, Research Design, Viruses, RNA, Viral, Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [Medical Subject Headings], Female, Estudios de seguimiento, Pathogens, VIH-1, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleosides::Deoxyribonucleosides::Dideoxynucleosides [Medical Subject Headings], medicine.drug, Research Article, Glomerular Filtration Rate, Adult, Efavirenz, Chemicals and Drugs::Organic Chemicals::Nitriles::Rilpivirine [Medical Subject Headings], Diseases::Chemically-Induced Disorders::Drug-Related Side Effects and Adverse Reactions [Medical Subject Headings], Clinical Research Design, Anti-HIV Agents, Phenomena and Processes::Cell Physiological Phenomena::Cell Count::Blood Cell Count::Leukocyte Count::Lymphocyte Count::CD4 Lymphocyte Count [Medical Subject Headings], Research and Analysis Methods, Internal medicine, Microbial Control, Virology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], Retroviruses, medicine, VIH (Virus), Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], Biology and life sciences, business.industry, HIV (Viruses), Lentivirus, HIV, Didesoxinucleósidos, Cell Biology, Antiretroviral agents, Diagnostic medicine, Surgery, CD4 Lymphocyte Count, Benzoxazinas, Adverse Events, Combinación de medicamentos, business
Abstract

OBJECTIVES: Based on data from clinical practice, we evaluated the effectiveness and safety of switching to abacavir/lamivudine plus rilpivirine (ABC/3TC+RPV) treatment in virologically suppressed HIV-1-infected patients. METHODS: We performed a multicenter, non-controlled, retrospective study of HIV-1-infected patients who switched treatment to ABC/3TC+RPV. Patients had an HIV-RNA

Published
2016

7. Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure

Author

José Antonio Olmedo Sánchez, Natalia Chueca, M. A. Martínez, José L. Hernández, María Dolores Mérida, Federico García, David Vinuesa, Josefa López, Marta Álvarez, Jose Ángel Fernández-Caballero, Complejo Hospitalario Universitario Granada. Servicio de Microbiología, Hospital Universitario San Cecilio. Instituto de Investigación Ibs. Granada, Granada (Andalucía), Spain., and This study was funded by Fondo de Investigación Sanitaria (PI12/01053, PI15/00713), RD12/0017/006 (Plan Nacional de I + D + I, Fondo Europeo de Desarrollo Regional-FEDER).

Subjects
0301 basic medicine, Male, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], ADN, España, HIV Infections, Pilot Projects, Proyectos piloto, HIV Integrase, Integrase, Piperazines, Raltegravir Potassium, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, 0302 clinical medicine, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Recombinases::Integrases [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cell Count::Blood Cell Count::Leukocyte Count::Lymphocyte Count::CD4 Lymphocyte Count [Medical Subject Headings], 030212 general & internal medicine, Treatment Failure, Sanger sequencing, Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], education.field_of_study, biology, Femenino, Middle Aged, Viral Load, Humanos, Infectious Diseases, Dolutegravir, Provirus, symbols, Compuestos heterocíclicos con 3 anillos, Female, Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [Medical Subject Headings], VIH-1, Viral load, Heterocyclic Compounds, 3-Ring, medicine.drug, Research Article, Adult, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], Genotype, Anti-HIV Agents, Pyridones, Population, Proviral DNA, 03 medical and health sciences, symbols.namesake, Estudios retrospectivos, Drug Resistance, Viral, Oxazines, medicine, Raltegravir potásico, Humans, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 3-Ring [Medical Subject Headings], HIV Integrase Inhibitors, education, Retrospective Studies, Salvage Therapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Pilot Projects [Medical Subject Headings], Mutación, Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], Organisms::Viruses::Proviruses [Medical Subject Headings], Integrasas, HIV, Recuento de linfocito CD4, Raltegravir, Virology, Infecciones por VIH, CD4 Lymphocyte Count, Carga viral, Regimen, 030104 developmental biology, chemistry, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Viral Load [Medical Subject Headings], DNA, Viral, Mutation, biology.protein, HIV-1, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA [Medical Subject Headings]
Abstract

Background: In our study, we have hypothesized that proviral DNA may show the history of mutations that emerged at previous failures to a Raltegravir containing regimen, in patients who are currently undetectable and candidates to simplification to a Dolutegravir containing regimen, in order to decide on once a day or twice a day dosing. Methods: We have performed a pilot, observational, retrospective, non interventional study, including 7 patients infected by HIV-1, all with a history of previous failure to a RAL containing regimen, that were successfully salvaged and had reached viral suppression. A genotypic viral Integrase region study was available for each patient at the moment of RAL failure. After an average (IQR) time of 48 months (29–53) Integrase resistance mutations in proviral DNA were studied. Results: All the patients were infected by HIV-1 B subtypes, with a mean age of 55 (range 43 to 56), originating from Spain, and 4 were women. Median viral load (log) and CD4 count at the moment of the study on proviral DNA was of 1.3 log cp/ml (range 0–1.47) and 765.5 cells/μL (range; 436.75–1023.75). The median time (IQR) between previous failure to RAL and the study on proviral DNA was 48 (29–53) months. At Raltegravir failure, N155H was detected in four patients, and other secondary mutations were detected in five patients (71.4 %). In proviral DNA, N155H was detected by population sequencing in three patients (42.8 %), and UDS demonstrated a 9.77 % relative abundance of N155H in the remaining patient. Sanger sequencing correctly identified all the secondary mutations. Conclusion: This is a pilot study that demonstrates the possibility of properly identifying N155H and some secondary mutations 29–53 months after failure., This study was funded by Fondo de Investigación Sanitaria (PI12/01053, PI15/00713), RD12/0017/006 (Plan Nacional de I + D + I, Fondo Europeo de Desarrollo Regional-FEDER).

Published
2016

8. Off-label use of rilpivirine in combination with emtricitabine and tenofovir in HIV-1-infected pediatric patients: A multicenter study

Author

Falcon-Neyra, Lola, Palladino, Claudia, Navarro Gómez, María Luisa, Soler-Palacín, Pere, González-Tomé, María Isabel, De Ory, Santiago J, Frick, Marie Antoinette, Fortuny, Clàudia, Noguera-Julian, Antoni, Moreno, Elena Bermúdez, Santos, Juan Luis, Olbrich, Peter, López-Cortés, Luis F, Briz, Verónica, Neth, Olaf, CoRISpe working group, Red de Investigación Cooperativa en Investigación en Sida (España), Instituto de Salud Carlos III, Fundação para a Ciência e a Tecnologia (Portugal), Universitat de Barcelona, Fundação para a Ciência e Tecnologia (Portugal), CoRISpe working group, [Falcon-Neyra,L, Neth,N, Olbrich,A] Unidad de Enfermedades Infecciosas e Inmunopatologias, Hospital Infantil Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain. [Palladino,C] Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal. [Palladino,C, Navarro Gómez,NL] Sección de Enfermedades Infecciosas, Servicio de Pediatría, Hospital General Universitario Gregorio Marañón, Madrid. [Soler-Palacín,P, Frick,MA] Unitat de Patologia Infecciosa i Immunodeficiències de Pediatria, Hospital Universitari Vall d’Hebron, Institut de Recerca Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona. [González-Tomé,MI] Servicio de Infecciosas Pediátricas, Hospital Universitario Doce de Octubre. [De Ory,SJ] Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid. [Fortuny,C, Noguera-Julian,A] Unitat d’Infectologia, Servei de Pediatria, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain. [Bermúdez Moreno,E] Servicio de Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Madrid. [Santos,JL] Unidad de Enfermedades Infecciosas e Inmunodeficiencias, Sección Urgencias de Pediatría, Hospital Universitario Virgen de las Nieves, Granada. [López-Cortés,LF] Enfermedades Infecciosas, Microbiología y Medicina Preventiva. Instituto de Biomedicina de Sevilla/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville. [ Briz,V] Unit of Viral Infection and Immunity, National Center for Microbiology, Institute of Health Carlos III, Majadahonda, Madrid, Spain., Financial support was provided by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en Sida (ISCIII-RETIC RD06/006, and RD12/0017/0035, and RD12/0017/0037) and FIPSE (grant number: 36-0910-10). This work has been also supported by grants from Instituto de Salud Carlos III (Ref. MPY 1039/14 to VB). CP is supported by the Portuguese Fundação para a Ciência e Tecnologia (FCT) (grant number SFRH/BPD/77448/2011, part of the EDCTP2 program supported by the European Union). VB is supported by the Miguel Servet program run by the Fondo de Investigación Sanitaria (ISCIII) (grant number CP13/00098).

Subjects
Male, medicine.medical_treatment, HIV Infections, Adolescents, Sida en els infants, Gastroenterology, Pediatrics, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, 0302 clinical medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cell Count::Blood Cell Count::Leukocyte Count::Lymphocyte Count::CD4 Lymphocyte Count [Medical Subject Headings], Emtricitabine, 030212 general & internal medicine, Child, Children, Adolescente, Chemicals and Drugs::Pharmaceutical Preparations::Dosage Forms::Tablets [Medical Subject Headings], Pediatria, Antiretrovirals, Comprimidos, Immunosuppression, Enzyme inhibitors, General Medicine, Antiretroviral therapy, Humanos, 3. Good health, ARN, Combinación emtricitabina, rilpivirina y tenofovir, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents [Medical Subject Headings], Treatment Outcome, Named Groups::Persons::Age Groups::Adolescent [Medical Subject Headings], Rilpivirine, Lípidos, RNA, Viral, Drug Therapy, Combination, Female, Estudios de seguimiento, VIH-1, Colesterol, Viral load, medicine.drug, medicine.medical_specialty, Adolescent, Anti-HIV Agents, Chemicals and Drugs::Lipids [Medical Subject Headings], 03 medical and health sciences, Pharmacotherapy, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA [Medical Subject Headings], Internal medicine, AIDS (Disease) in children, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], Chemicals and Drugs::Organic Chemicals::Nitriles::Rilpivirine::Emtricitabine, Rilpivirine, Tenofovir Drug Combination [Medical Subject Headings], medicine, VIH (Virus), Humans, Adverse effect, Tenofovir, Retrospective Studies, Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], business.industry, HIV (Viruses), Recuento de linfocito CD4, Off-Label Use, Antiretroviral agents, Chemicals and Drugs::Lipids::Sterols::Cholesterol [Medical Subject Headings], Discontinuation, Surgery, Carga viral, Regimen, Fármacos anti-VIH, chemistry, Inhibidors enzimàtics, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Viral Load [Medical Subject Headings], HIV-1, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

To assess the safety and efficacy of rilpivirine in combination with emtricitabine and tenofovir (RPV/FTC/TDF) as a once-daily single-tablet regimen (STR) in HIV-1-infected children and adolescents we performed a multicenter case series study of HIV-1-infected patients. Inclusion criteria were initiation of therapy with RPV/FTC/TDF before the age of 18. Patients were divided into undetectable viral load (uVL) group, HIV-1 RNA

Published
2016

9. Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010

Author

Felipe Fernández-Cuenca, Beatriz de Felipe, Luis F. López-Cortés, Alejandro Vallejo, Pompeyo Viciana, Francisco J. Martinez-Fernandez, Pilar Pérez-Romero, Manuel Leal, Rosario Mata, María Abad-Fernández, Mónica Trastoy, [de Felipe,B, Pérez-Romero,P, Martinez-Fernandez,FJ, Trastoy,M, Mata,RC, López-Cortés,LF, Viciana,P] Infectious Diseases Service, IBIS, Hospital Univeritario Virgen del Rocio, Seville, Spain. [Abad-Fernández,M, Vallejo,A] Laboratory of Immunovirology, Infectious Diseases Service, Instituto Ramón y Cajal de Investigaciones Cientificas (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain.[Fernandez-Cuenca,F] Microbiology Service Hospital Virgen Macarena Seville, Spain. [Leal,M, Vallejo,A] Laboratory of Immunovirology, Infectious Diseases Service, IBIS, Virgen del Rocío University Hospital, Seville, Spain., and This study was supported in part by Fondo de Investigación Sanitaria (FIS) 07/0070, Redes Temáticas de Investigación Cooperativa en Salud (RETICS) Red de Investigación en SIDA (RIS) RD06/0006/0021 and RD/06/0006/0034, and Servicio Andaluz de Salud, Consejería de Salud 0407/2007.

Subjects
Male, Immigration, Human immunodeficiency virus (HIV), HIV Infections, Drug resistance, resistance mutation, medicine.disease_cause, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Mutación Missense, HIV Protease, Genotype, Prevalence, Cluster Analysis, Phylogeny, media_common, Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Resistance mutation, HIV Reverse Transcriptase, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation::Mutation, Missense [Medical Subject Headings], Infectious Diseases, Cohort, Female, Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Phenomena and Processes::Microbiological Phenomena::Drug Resistance, Microbial::Drug Resistance, Viral [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA [Medical Subject Headings], Adult, Anti-HIV Agents, media_common.quotation_subject, Molecular Sequence Data, Mutation, Missense, Emigrants and Immigrants, immigrant, Biology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Cluster Analysis [Medical Subject Headings], non-B HIV-1 subtypes, lcsh:Infectious and parasitic diseases, Virology, Drug Resistance, Viral, medicine, Humans, lcsh:RC109-216, Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], Resistance (ecology), Research, Andalucía, Sequence Analysis, DNA, Emigrantes e Inmigrantes, Spain, Named Groups::Persons::Emigrants and Immigrants [Medical Subject Headings], Information Science::Information Science::Data Collection::Vital Statistics::Morbidity::Prevalence [Medical Subject Headings], HIV-1
Abstract

Background Most of the non-B HIV-1 subtypes are predominant in Sub-Saharan Africa and India although they have been found worldwide. In the last decade, immigration from these areas has increased considerably in Spain. The objective of this study was to evaluate the prevalence of non-B subtypes circulating in a cohort of HIV-1-infected immigrants in Seville, Southern Spain and to identify drug resistance-associated mutations. Methods Complete protease and first 220 codons of the reverse transcriptase coding regions were amplified and sequenced by population sequencing. HIV-1 subtypes were determined using Stanford University Drug Resistance Database, and phylogenetic analysis was performed comparing multiple reported sequences. Drug resistance mutations were defined according to the International AIDS Society-USA. Results From 2000 to 2010 a total of 1,089 newly diagnosed HIV-1-infected patients were enrolled in our cohort. Of these, 121 were immigrants, of which 98 had ethical approval and informed consent to include in our study. Twenty-nine immigrants (29/98, 29.6%) were infected with non-B subtypes, of which 15/29 (51.7%) were CRF02-AG, mostly from Sub-Saharan Africa, and 2/29 (6.9%) were CRF01-AE from Eastern Europe. A, C, F, J and G subtypes from Eastern Europe, Central-South America and Sub-Saharan Africa were also present. Some others harboured recombinant forms CRF02-AG/CRF01-AE, CRF2-AG/G and F/B, B/C, and K/G, in PR and RT-coding regions. Patients infected with non-B subtypes showed a high frequency of minor protease inhibitor resistance mutations, M36I, L63P, and K20R/I. Only one patient, CRF02_AG, showed major resistance mutation L90M. Major RT inhibitor resistance mutations K70R and A98G were present in one patient with subtype G, L100I in one patient with CRF01_AE, and K103N in another patient with CRF01_AE. Three patients had other mutations such as V118I, E138A and V90I. Conclusions The circulation of non-B subtypes has significantly increased in Southern Spain during the last decade, with 29.6% prevalence, in association with demographic changes among immigrants. This could be an issue in the treatment and management of these patients. Resistance mutations have been detected in these patients with a prevalence of 7% among treatment-naïve patients compared with the 21% detected among patients under HAART or during treatment interruption.

Published
2011

10. Added Value of Deep Sequencing Relative to Population Sequencing in Heavily Pre-Treated HIV-1-Infected Subjects

Author

Roger Paredes, Alexander Thielen, Miguel Álvarez-Tejado, Federico García, David Dalmau, Lidia Ruiz, Christian Pou, Bonaventura Clotet, Francisco M. Codoñer, Rafael Delgado, [Codoner,FM, Pou,C, Ruiz,E, Clotet,B]Institut de Recerca de la SIDA irsiCaixa-HIVACAT, Badalona, Spain. [Clotet,B, and Paredes,R] Unitat VIH, Hospital Universitari Germans Trias I Pujol, Badalona, Spain. [Thielen,A] Max Planck Institute für Informatik, Saarbücken, Germany. [García,F] Hospital San Cecilio, Granada, Spain. [Delgado,R] Hospital 12 de Octubre, Madrid, Spain [Dalmau,D]Hospital Universitari Mutua Terrassa, Terrassa, Spain. [Álvarez-Tejado,M] Roche Diagnostics SL, Sant Cugat del Vallés, Spain

Subjects
Male, Insuficiencia del Tratamiento, Epidemiology, Pyridines, lcsh:Medicine, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Outcome and Process Assessment (Health Care)::Outcome Assessment (Health Care)::Treatment Outcome::Treatment Failure [Medical Subject Headings], Etravirine, Salvage therapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::High-Throughput Nucleotide Sequencing [Medical Subject Headings], HIV Infections, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyridines [Medical Subject Headings], Agentes Anti VIH, Secuenciación de Nucleótidos de Alto Rendimiento, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Indinavir, Treatment Failure, lcsh:Science, Masculino, Darunavir, 0303 health sciences, education.field_of_study, Molecular Epidemiology, Sulfonamides, Multidisciplinary, Sulfonamidas, Femenino, High-Throughput Nucleotide Sequencing, Pyrrolidinones, Humanos, 3. Good health, Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Drug Resistance::Drug Resistance, Microbial::Drug Resistance, Viral [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation::Mutation, Missense [Medical Subject Headings], Chemicals and Drugs::Organic Chemicals::Sulfur Compounds::Sulfones::Sulfonamides [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents [Medical Subject Headings], Anti-Retroviral Agents, HIV epidemiology, Chemicals and Drugs::Heterocyclic Compounds::Pyrans::Pyrones [Medical Subject Headings], Medicine, Infectious diseases, Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [Medical Subject Headings], Female, Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], VIH-1, Tipranavir, medicine.drug, Research Article, Farmacorresistencia Viral, Genotype, Anti-HIV Agents, Population, Viral diseases, Biology, Pironas, Deep sequencing, Infectious Disease Epidemiology, Terapia Recuperativa, 03 medical and health sciences, Pirrolidinonas, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrrolidines::Pyrrolidinones [Medical Subject Headings], Piridinas, Raltegravir Potassium, Drug Resistance, Viral, medicine, Humans, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents [Medical Subject Headings], education, 030304 developmental biology, Salvage Therapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Salvage Therapy [Medical Subject Headings], Mutación, Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], Anatomy::Urogenital System::Genitalia::Genitalia, Female [Medical Subject Headings], 030306 microbiology, lcsh:R, Anatomy::Urogenital System::Genitalia::Genitalia, Male [Medical Subject Headings], HIV, Raltegravir, Virology, Infecciones por VIH, Pyrones, Agentes Antirretrovirales, Mutation, HIV-1, lcsh:Q, Genotipo
Abstract

OBJECTIVE: To explore the potential of deep HIV-1 sequencing for adding clinically relevant information relative to viral population sequencing in heavily pre-treated HIV-1-infected subjects. METHODS: In a proof-of-concept study, deep sequencing was compared to population sequencing in HIV-1-infected individuals with previous triple-class virological failure who also developed virologic failure to deep salvage therapy including, at least, darunavir, tipranavir, etravirine or raltegravir. Viral susceptibility was inferred before salvage therapy initiation and at virological failure using deep and population sequencing genotypes interpreted with the HIVdb, Rega and ANRS algorithms. The threshold level for mutant detection with deep sequencing was 1%. RESULTS: 7 subjects with previous exposure to a median of 15 antiretrovirals during a median of 13 years were included. Deep salvage therapy included darunavir, tipranavir, etravirine or raltegravir in 4, 2, 2 and 5 subjects, respectively. Self-reported treatment adherence was adequate in 4 and partial in 2; one individual underwent treatment interruption during follow-up. Deep sequencing detected all mutations found by population sequencing and identified additional resistance mutations in all but one individual, predominantly after virological failure to deep salvage therapy. Additional genotypic information led to consistent decreases in predicted susceptibility to etravirine, efavirenz, nucleoside reverse transcriptase inhibitors and indinavir in 2, 1, 2 and 1 subject, respectively. Deep sequencing data did not consistently modify the susceptibility predictions achieved with population sequencing for darunavir, tipranavir or raltegravir. CONCLUSIONS: In this subset of heavily pre-treated individuals, deep sequencing improved the assessment of genotypic resistance to etravirine, but did not consistently provide additional information on darunavir, tipranavir or raltegravir susceptibility. These data may inform the design of future studies addressing the clinical value of minority drug-resistant variants in treatment-experienced subjects. Yes OBJETIVO: Para explorar el potencial de profundidad del VIH-1 la secuencia de la adición de información clínica relevante respecto a la población viral secuenciación en gran medida de pre-tratamiento del VIH-1 sujetos infectados. MÉTODOS: En un estudio de prueba de concepto, profundo secuencia se comparó con la secuencia de la población en el VIH-1-las personas infectadas con el anterior, tres clases de fracaso virológico que también desarrollaron falla virológica a profundidad la terapia de rescate, incluyendo, al menos, el darunavir, tipranavir, etravirina o raltegravir. La susceptibilidad del virus se dedujo antes de iniciar el tratamiento de rescate y en el fracaso virológico con profunda genotipos de secuenciación y de la población interpretarse con los algoritmos HIVdb, Rega y la ANRS. El nivel de umbral para la detección de mutantes con profunda secuenciación fue del 1%. Resultados: 7 sujetos con exposición previa a una mediana de 15 antirretrovirales durante una mediana de 13 años fueron incluidos. profunda terapia de rescate incluyó darunavir, tipranavir, etravirina o raltegravir en 4, 2, 2 y 5 sujetos, respectivamente. Auto-reporte de la adherencia al tratamiento fue adecuado en cuatro y parcial en dos, una persona sufrió la interrupción del tratamiento durante el seguimiento. profunda secuenciación detecta todas las mutaciones detectadas por la secuenciación de la población e identificar las mutaciones de resistencia adicional en todos, pero cada uno, sobre todo después del fracaso virológico de profundidad terapia de rescate. Información genotípica adicional condujo a una disminución constante en la susceptibilidad a etravirina predijo, efavirenz, los inhibidores nucleósidos de la transcriptasa inversa e indinavir en 2, 1, 2 y 1 sujeto, respectivamente. profunda secuencia de datos no siempre modificar las predicciones susceptibilidad de la población consigue con la secuencia de darunavir, tipranavir o raltegravir. CONCLUSIONES: En este subgrupo de fuertemente pretratados personas, profunda mejorar la secuencia de la evaluación de la resistencia genotípica a la etravirina, pero no siempre proporcionan información adicional sobre darunavir, tipranavir o susceptibilidad a raltegravir. Estos datos pueden informar el diseño de futuros estudios clínicos frente a los valores de la minoría variantes resistentes a los medicamentos en los sujetos con experiencia en tratamientos.

Published
2011

11. Long-term assessment of didanosine, lamivudine, and efavirenz in antiretroviral-naive patients: 3-year follow-up

Author

Manuel López, Javier de la Torres, Antonio Rivero, María Carmen Gálvez, Fernando Lozano, Rosario Palacios, Jesús Santos, Luis F. López-Cortés, María José Ríos, Grupo andaluz para el estudio de las enfermedades infecciosas (GAEI), [Santos González,JL, and Palacios Muñoz,R] Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Lozano,F] Hospital de Valme, Sevilla, Spain. [López,M] Hospital Virgen de las Nieves, Granada, Spain. [Gálvez,MC] Hospital Torrecárdenas, Almería, Spain. [las Torres,J de] Hospital Costa del Sol, Marbella, Spain. [López-Cortés,LF] Hospital Virgen del Rocío, Sevilla, Spain. [Ríos,MJ] Hospital Virgen Macarena, Sevilla, Spain. [Rivero Román,A] Hospital Reina Sofía, Córdoba, Spain.

Subjects
Cyclopropanes, HIV Infections, Diseases::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, Carga Viral, Antiretroviral naive, Medicine, Didanosine, Adulto, Quimioterapia Combinada, Lamivudine, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidine Nucleosides::Cytidine::Deoxycytidine::Zalcitabine::Lamivudine [Medical Subject Headings], Viral Load, Humanos, Treatment Outcome, Infectious Diseases, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents [Medical Subject Headings], Alkynes, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Nucleic Acid Synthesis Inhibitors::Reverse Transcriptase Inhibitors [Medical Subject Headings], Toxicity, Cohort, Reverse Transcriptase Inhibitors, Drug Therapy, Combination, VIH-1, Didanosina, Inhibidores de Transcriptasa Inversa, medicine.drug, Adult, medicine.medical_specialty, Efavirenz, Anti-HIV Agents, Resultado del Tratamiento, Immunology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Therapy, Combination [Medical Subject Headings], Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Purines::Purine Nucleosides::Inosine::Didanosine [Medical Subject Headings], Virology, Internal medicine, Humans, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings], Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], business.industry, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Follow-Up Studies [Medical Subject Headings], Infecciones por VIH, Benzoxazines, Regimen, chemistry, Multicenter study, Benzoxazinas, Fármacos Anti-VIH, Estudios de Seguimiento, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Viral Load [Medical Subject Headings], Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Oxazines::Benzoxazines [Medical Subject Headings], HIV-1, business, Follow-Up Studies
Abstract

Clinical Trial; Journal Article; Multicenter Study; The aim of this study was to evaluate the long-term efficacy and safety of didadosine (ddI), lamivudine (3TC), and efavirenz (EFV). This was a follow-up to the VESD study, a 12-month open-label, observational, multicenter study of adult patients with HIV infection who started antiretroviral treatment with the ddI-3TC-EFV once-daily regimen. Of the 167 patients originally included, 106 patients remained on the same triple therapy at the end of the study (1 year), and they were offered an extra 24 months of follow-up; 96 were enrolled in this study (VESD-2). Seventy patients out of the initial cohort were still on the same regimen at month 36, with 97% of them with plasma viral load

Published
2008

12. Structured intermittent interruption of chronic HIV infection treatment with highly active antiretroviral therapy: Effects on leptin and TNF-alpha

Author

R. Garcia-Juárez, José A. Girón-González, C. Fernández Gutiérrez del Álamo, M. Montes de Oca Arjona, Andrés Martín-Aspas, R. Pérez-Cano, [Montes de Oca-Arjona, M, Pérez-Cano, R, García-Juarez, R, Martín-Aspas, A, and Girón-Gonzáez, JA] Internal Medicine Services, Hospital Universitario Puerta del Mar, Cádiz, Spain. [Fernández-Gutiérrez del Álamo, C] Microbiology Services, Hospital Universitario Puerta del Mar, Cádiz, Spain.

Subjects
CD4-Positive T-Lymphocytes, Male, Leptin, HIV Infections, Gastroenterology, Anatomy::Hemic and Immune Systems::Blood::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Tumor Necrosis Factors::Tumor Necrosis Factor-alpha [Medical Subject Headings], Immunopathology, Antiretroviral Therapy, Highly Active, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Receptors, Tumor Necrosis Factor, Type II [Medical Subject Headings], Factor de Necrosis Tumoral alfa, Sida, Chemicals and Drugs::Lipids::Glycerides::Triglycerides [Medical Subject Headings], Phenomena and Processes::Microbiological Phenomena::Virus Physiological Phenomena::Viral Load [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration Schedule [Medical Subject Headings], Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Chronic Disease [Medical Subject Headings], biology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Therapy, Combination::Antiretroviral Therapy, Highly Active [Medical Subject Headings], Estudios de Casos y Controles, Chemicals and Drugs::Polycyclic Compounds::Steroids::Cholestanes::Cholestenes::Cholesterol [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Skinfold Thickness [Medical Subject Headings], Reference Standards, Viral Load, Grosor de Pliegues Cutáneo, Skinfold Thickness, Infectious Diseases, medicine.anatomical_structure, Treatment Outcome, Cholesterol, Receptors, Tumor Necrosis Factor, Type I, RNA, Viral, Receptors, Leptin, Female, Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [Medical Subject Headings], Viral disease, Viral load, Colesterol, Adult, medicine.medical_specialty, T cell, Receptores Tipo II del Factor de Necrosis Tumoral, Immunology, Adipokine, Check Tags::Male [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Adipokine::Receptors, Leptin [Medical Subject Headings], Drug Administration Schedule, Triglicéridos, Receptores de Leptina, Acquired immunodeficiency syndrome (AIDS), Leptina, Virology, Internal medicine, medicine, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Humans, Receptors, Tumor Necrosis Factor, Type II, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Viral [Medical Subject Headings], Receptores Tipo I de Factores de Necrosis Tumoral, Triglycerides, Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Adipokines::Leptin [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings], Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], business.industry, Tumor Necrosis Factor-alpha, Enfermedad crónica, Leptin receptor, human, Linfocitos T CD4-Positivos, Recuento de Linfocito CD4, biology.organism_classification, medicine.disease, CD4 Lymphocyte Count, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Cytological Techniques::Cell Count::Blood Cell Count::Leukocyte Count::Lymphocyte Count::CD4 Lymphocyte Count [Medical Subject Headings], Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CD::Receptors, Tumor Necrosis Factor, Type II [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Weights and Measures::Reference Standards [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Case-Control Studies, Chronic Disease, HIV-1, Receptores de leptina, humanos, business, ARN Viral
Abstract

This is a copy of an article published in the AIDS Research and Human Retroviruses © 2011 [copyright Mary Ann Liebert, Inc.]; AIDS Research and Human Retroviruses is available online at: http://online.liebertpub.com. Comparative Study; Journal Article; The changes in nutritional parameters and adipocytokines after structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection are analyzed. Twenty-seven patients with chronic HIV infection (median CD4+ T cell count/microl: nadir, 394; at the beginning of structured interruptions, 1041; HIV viral load: nadir, 41,521 copies/ml; at the beginning of structured interruptions

Published
2006

13. Effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children: 3 years of follow-up. Long-term response to nelfinavir in children

Author

María Isabel de José, María Ángeles Muñoz-Fernández, Rosa Resino, Marisa Navarro, Beatriz Larrú, Juan Antonio León, María José Mellado, Salvador Resino, José Tomás Ramos, José María Bellón, [Resino,D, Bellón,JM, Resino,R, Muñoz-Fernández,MA] Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain. [Larrú,B, De José,MI] Pediatría-Infecciosas, Hospital Universitario 'La Paz', Madrid, Spain. [Navarro,M] Pediatría-Infecciosas, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain. [Léon,JA] Pediatría-Infecciosas, Hospital Universitario 'Virgen de Rocío', Sevilla, Spain. [Ramos,JT] Inmuno-Pediatría, Hospital Universitario '12 de Octubre', Madrid, Spain. [Mellado,MJ] Pediatría-Infecciosas, Hospital Universitario 'Carlos III', Madrid, Spain., and Fundación para la Investigación y la Prevención del SIDA en España (FIPSE) (grant 12456/03). Fundación para la Investigación Sanitaria (FIS) del Ministerio de Sanidad y Consumo (PI040883, PI052479, PI052472, PI052411), Plan Nacional de Salud (SAF 2003-09209, SAF-2004-06778), Red Temática Cooperativa de investigación en SIDA (RIS G03/173) of FIS, and Red Temática Cooperativa de investigación en Genética (RIG C03/07) of FIS.

Subjects
Male, Pediatrics, HIV Infections, Diseases::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Preescolar, Carga Viral, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cell Count::Blood Cell Count::Leukocyte Count::Lymphocyte Count::CD4 Lymphocyte Count [Medical Subject Headings], Antiretroviral Therapy, Highly Active, Prospective Studies, Masculino, Prospective cohort study, Child, Nelfinavir, Named Groups::Persons::Age Groups::Child::Child, Preschool [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Therapy, Combination::Antiretroviral Therapy, Highly Active [Medical Subject Headings], Femenino, Viral Load, Humanos, Infectious Diseases, Transmisión Vertical de Enfermedad Infecciosa, Niño, Child, Preschool, Health Care::Environment and Public Health::Public Health::Disease Transmission, Infectious::Infectious Disease Transmission, Vertical [Medical Subject Headings], Female, Sample collection, VIH-1, Viral load, medicine.drug, Research Article, medicine.medical_specialty, Check Tags::Male [Medical Subject Headings], Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Isoquinolines::Nelfinavir [Medical Subject Headings], lcsh:Infectious and parasitic diseases, medicine, Humans, Protease inhibitor (pharmacology), lcsh:RC109-216, Named Groups::Persons::Age Groups::Child [Medical Subject Headings], Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], business.industry, Recuento de Linfocito CD4, Odds ratio, HIV Protease Inhibitors, Terapia Antirretroviral Altamente Activa, Infecciones por VIH, Infectious Disease Transmission, Vertical, CD4 Lymphocyte Count, Clinical trial, Check Tags::Female [Medical Subject Headings], El Niño, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Viral Load [Medical Subject Headings], Immunology, HIV-1, business, Follow-Up Studies
Abstract

Clinical Trial; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't; BACKGROUND Antiretroviral treatment (ART) in children has special features and consequently, results obtained from clinical trials with antiretroviral drugs in adults may not be representative of children. Nelfinavir (NFV) is an HIV-1 Protease Inhibitor (PI) which has become as one of the first choices of PI for ART in children. We studied during a 3-year follow-up period the effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children. METHODS Forty-two vertically HIV-infected children on HAART with NFV were involved in a multicentre prospective study. The children were monitored at least every 3 months with physical examinations, and blood sample collection to measure viral load (VL) and CD4+ cell count. We performed a logistic regression analysis to determinate the odds ratio of baseline characteristics on therapeutic failure. RESULTS Very important increase in CD4+ was observed and VL decreased quickly and it remained low during the follow-up study. Children with CD4+ 25% at 9 months of follow-up. HIV-infected children who achieved undetectable viral load (uVL) were less than 40% in each visit during follow-up. Nevertheless, HIV-infected children with VL >5000 copies/ml were less than 50% during the follow-up study. Only baseline VL was an important factor to predict VL control during follow-up. Virological failure at defined end-point was confirmed in 30/42 patients. Along the whole of follow-up, 16/42 children stopped HAART with NFV. Baseline characteristics were not associated with therapeutic change. CONCLUSION NFV is a safe drug with a good profile and able to achieve an adequate response in children. Yes

Published
2006

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