36 results on '"Gurbindo D"'
Search Results
2. CAUSES OF DEATH IN HIV-1 VERTICALLY INFECTED PAEDIATRIC PATIENTS IN MADRID (SPAIN) FROM 1982 TO 2008: OP10
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Climent, F, Palladino, C, De Jose, I, De Ory, S J, Bellon, J M, Guillen, S, Gurbindo, D, Gonzalez-Tome, I, Mellado, J, Perez, J M, Ramos, J T, Calvo, C, and Muñoz-Fernández, A
- Published
- 2010
3. Role of antiretroviral therapies in mucocutaneous manifestations in HIV-infected children over a period of two decades
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Reula, E Seoane, Bellon, J. M., Gurbindo, D, and Muñoz-Fernandez, M. A.
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- 2005
4. HIV-infected children with moderate/severe immune-suppression: changes in the immune system after highly active antiretroviral therapy
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RESINO, S., GALÁN, I., PÉREZ, A., LEÓN, J. A., SEOANE, E., GURBINDO, D., and MUÑOZ-FERNÁNDEZ, M. ÁNGELES
- Published
- 2004
5. Recovery of T-cell subsets after antiretroviral therapy in HIV-infected children
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Resino, S., Bellón, J. M, Gurbindo, D., León, J. A., and Muñoz-Fernández, M Á
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- 2003
6. Naïve and memory CD4+ T cells and T cell activation markers in HIV-1 infected children on HAART
- Author
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Resino, S., Navarro, J., Bellón, J. M., Gurbindo, D., León, J. A., and Muñoz-Fernández, M. A.
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- 2001
7. Clinical Relevance of Cytokine Production in HIV-1 Infection in Children on Antiretroviral Therapy
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Resino, S., Bellón, J. M, Sánchez-Ramón, S., Gurbindo, D., and Muñóz-Fernandez, M A.
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- 2000
8. Immunological and virological effects of highly active antiretroviral therapy in two HIV-1 infected children
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Leon, J A, Leal, M, Lissen, E, Gurbindo, D, and Muñoz-Fernández, M A
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- 2000
9. Multicenter study for the evaluation of the antibody response against salmonella typhi Vi vaccination (EMPATHY) for the diagnosis of Anti-polysaccharide antibody production deficiency in patients with primary immunodeficiency
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Sanchez-Ramon, S., de Gracia, J., Garcia-Alonso, A. M., Rodriguez Molina, J. J., Melero, J., de Andres, A., Garcia Ruiz de Morales, J. M., Ferreira, A., Ocejo-Vinyals, J. G., Cid, J. J., Garcia Martinez, J. M., Lasheras, T., Vargas, M. L., Gil-Herrera, J., Garcia Rodriguez, M. C., Castaner, J. L., Gonzalez Granado, L. I., Allende, L. M., Soler-Palacin, P., Herraiz, L., Lopez Hoyos, M., Bellon, J. M., Silva, G., Gurbindo, D. M., Carbone, J., Rodriguez-Sainz, C., Matamoros, N., Parker, A. R., Fernandez-Cruz, E., and EMPATHY Grp
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0301 basic medicine ,Male ,Salmonella ,fiebre tifoidea ,humanos ,Specific polysaccharide antibody response ,medicine.disease_cause ,Salmonella typhi ,Hypogammaglobulinemia ,Agammaglobulinemia ,estudios prospectivos ,formación de anticuerpos ,Immunology and Allergy ,Prospective Studies ,mediana edad ,anciano ,biology ,Polysaccharides, Bacterial ,Vaccination ,CVID ,interacciones huésped-patógeno ,inmunodeficiencia variable común ,Typhim Vi ,Middle Aged ,adulto ,Antibodies, Bacterial ,adulto joven ,Host-Pathogen Interactions ,Female ,vacunas de la fiebre tifoidea y paratifoidea ,Antibody ,enzimoinmunoanálisis por adsorción ,Adult ,síndromes de inmunodeficiencia ,Immunology ,Enzyme-Linked Immunosorbent Assay ,Antibodies ,03 medical and health sciences ,Young Adult ,vacunación ,Antigen ,Polysaccharides ,polisacáridos ,medicine ,Humans ,inmunoglobulina G ,Typhoid Fever ,Vi polysaccharide antigen ,Pneumococcal polysaccharide antigens, Typhim Vi ,Aged ,business.industry ,Common variable immunodeficiency ,Typhoid-Paratyphoid Vaccines ,Immunologic Deficiency Syndromes ,medicine.disease ,Virology ,030104 developmental biology ,Common Variable Immunodeficiency ,Immunoglobulin G ,anticuerpos ,Antibody Formation ,biology.protein ,Primary immunodeficiency ,business ,Pneumococcal polysaccharide antigens - Abstract
Evaluation of specific antibody (Ab) response to polysaccharide antigens is essential for diagnosis of primary immunodeficiencies. We assessed the specific Ab responses to the pneumococcal-polysaccharide (PPV) and to Salmonella typhi-polysaccharide (TyphimVi) vaccines in a prospective study (EMPATHY) in patients with common variable immunodeficiency (CVID-Group, n = 22), hypogammaglobulinemia (HYPOG-Group; n = 27) and healthy controls (HC-Group; n = 16). Specific Ab concentrations in response to PPV and to TyphimVi vaccines were measured by ELISA (The Binding Site, UK), defining 3-fold increase as normal response (Ratio:3 x). The RatioTyphimVi:3 x was significantly greater in HC than in CVID-Group (p < 0.0001), but not than HYPOG-Group (p = 0.138). However, the RatioPPV:3 x showed no significant differences among the three groups. By ROC analysis, TyphimVi better differentiated HC from CVID (AUC:0.893, IC95%: 0.791-0.996, p < 0.0001) than PPV. Our results suggest that the use of specific Ab response to TyphimVi could represent a complementary assay for the diagnosis of anti-polysaccharide Ab production deficiency in patients with CVID.
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- 2016
10. The immunological and virological consequences of planned treatment interruptions in children with HIV infection
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Klein, Nigel, Sefe, Delali, Mosconi, Ilaria, Zanchetta, Marisa, Castro, Hannah, Jacobsen, Marianne, Jones, Hannah, Bernardi, Stefania, Pillay, Deenan, Giaquinto, Carlo, Walker, A. Sarah, Gibb, Diana M., De Rossi, Anita, Paediatric, European Network for Treatment of AIDS 11 Trial Team including Aboulker JP, Ananworanich, J, Babiker, A, Belfrage, E, Bernardi, S, Blanche, S, Bohlin, Ab, Bologna, R, Burger, Dm, Butler, K, Castelli Gattinara, G, Castro, H, Clayden, P, Compagnucci, A, Darbyshire, Jh, Debré, M, Faye, A, de Groot, R, della Negra, M, Duiculescu, D, Giaquinto, C, Gibb, Dm, Grosch Wörner, I, Hainault, M, Harper, L, Klein, N, Lallemant, M, Levy, J, Lyall, H, Marczynska, M, Mardarescu, M, Mellado Peña, Mj, Nadal, D, Niehues, T, Peckham, C, Pillay, D, Ramos Amador, Jt, Rosado, L, Rosso, R, Rudin, C, Saidi, Y, Scherpbier, Hj, Sharland, M, Stevanovic, M, Thorne, C, Tovo, Pier Angelo, Tudor Williams, G, Valerius, N, Walker, As, Welch, S, Wintergerst, U, Aboulker, Jp, Mofenson, L, Moye, J, Saïdi, Y, Cressey, Tr, Jacqz Aigrain, E, Khoo, S, Tréluyer, Jm, De Rossi, A, Ngo Giang Huong, N, Muñoz Fernandez, Ma, Hill, C, Lepage, P, Pozniak, A, Vella, S, Hadjou, G, Léonardo, S, Riault, Y, Buck, L, Farrelly, L, Forcat, S, Harrison, L, Horton, J, Johnson, D, Moore, S, Taylor, C, Chalermpantmetagul, S, Peongjakta, R, Chailert, S, Fregonese, F, Jourdain, G, Butler, D, Carlton, C, Collins, D, Kao, G, Van Buskirk, S, Watson, S, Corradini, S, Floret, D, Le Thi, Tt, Monpoux, F, Cottalorda, J, Lefebvre, Jc, Mellul, S, Boudjoudi, N, Firtion, G, Denon, M, Picard, F, Beniken, D, Damond, F, Alexandre, G, Tricoire, J, Nicot, F, Krivine, A, Rivaux, D, Chaix, Ml, Notheis, G, Strotmann, G, Schlieben, S, Rampon, O, Zanchetta, M, Ginocchio, F, Viscoli, C, Martino, A, Pontrelli, G, Concato, C, Mazza, A, Rossetti, G, Dobosz, S, Oldakowska, A, Popielska, J, Kaflik, M, Stanczak, J, Stanczack, G, Dyda, T, González Tomé, Mi, Delgado García, R, Fernandez Gonzalez, Mt, Martín Fontelos, P, Piñeiro Pérez, R, Penin, M, Garcia Mellado, I, Medina, Af, Ascencion, B, Garcia Bermejo, I, Garcia Vela, Ja, Martin Rubio, I, Gurbindo, D, Navarro Gomez, Ml, Jimenez, Jl, Garcia Torre, A, José Gómez, Mi, García Rodriguez, Mc, Moreno Pérez, D, Núñez Cuadros, E, Asensi Botet, F, Pérez, A, Pérez Tamarit, Md, Gobernado Serrano, M, Gonzales Molina, A, Kalhert, C, Dobrovoljac, M, Berger, C, Nobile, G, Reinhard, S, Schupbach, J, Bunupuradah, T, Puthanakit, T, Pancharoen, C, Butterworth, O, Phasomsap, C, Jupimai, T, Ubolyam, S, Phanuphak, P, Mai, C, Kanjanavanit, S, Namwong, T, Chutima, D, Raksasang, M, Foster, C, Hamadache, D, Campbell, S, Newbould, C, Monrose, C, Patel, D, Kaye, S, Seery, P, Wildfire, A, Novelli, V, Shingadia, D, Moshal, K, Flynn, J, Clapson, M, Allen, A, Spencer, L, Depala, M, Jacobsen, M, Mcmaster, P, Phipps, M, Orendi, J, Farmer, C, Liebeschuetz, S, Sodeinde, O, Wong, S, Heath, Y, Scott, S, Gandhi, K, Lewis, P, Daglish, J, Weiner, L, Famiglietti, M, Rana, S, Yu, P, Roa, J, Puga, A, Haerry, A, and Inma, A.
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CD31 ,Genetics and Molecular Biology (all) ,CD4-Positive T-Lymphocytes ,Time Factors ,T-CELL RECONSTITUTION ,ACTIVE ANTIRETROVIRAL THERAPY, STRUCTURED TREATMENT INTERRUPTION, T-CELL RECONSTITUTION, HIV-1-INFECTED CHILDREN, IMMUNE RECONSTITUTION, THYMIC OUTPUT, 1-INFECTED CHILDREN ,Adolescent ,Anti-Retroviral Agents ,CD8-Positive T-Lymphocytes ,Child ,Child, Preschool ,Drug Administration Schedule ,HIV Infections ,Humans ,Immunophenotyping ,Lymphocyte Count ,Treatment Outcome ,Viral Load ,Agricultural and Biological Sciences (all) ,Biochemistry, Genetics and Molecular Biology (all) ,Medicine (all) ,Biochemistry ,law.invention ,IMMUNE RECONSTITUTION ,0302 clinical medicine ,Randomized controlled trial ,law ,030212 general & internal medicine ,HIV-1-INFECTED CHILDREN ,0303 health sciences ,Multidisciplinary ,ACTIVE ANTIRETROVIRAL THERAPY ,3. Good health ,Medicine ,Off Treatment ,Poverty-related infectious diseases Infectious diseases and international health [N4i 3] ,THYMIC OUTPUT ,Viral load ,Research Article ,Science ,1-INFECTED CHILDREN ,Auto-immunity, transplantation and immunotherapy [N4i 4] ,03 medical and health sciences ,Acquired immunodeficiency syndrome (AIDS) ,medicine ,Preschool ,030304 developmental biology ,business.industry ,medicine.disease ,Clinical trial ,Immunology ,STRUCTURED TREATMENT INTERRUPTION ,business ,CD8 - Abstract
Contains fulltext : 126098.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To evaluate the immunological and viral consequences of planned treatment interruptions (PTI) in children with HIV. DESIGN: This was an immunological and virological sub-study of the Paediatric European Network for Treatment of AIDS (PENTA) 11 trial, which compared CD4-guided PTI of antiretroviral therapy (ART) with continuous therapy (CT) in children. METHODS: HIV-1 RNA and lymphocyte subsets, including CD4 and CD8 cells, were quantified on fresh samples collected during the study; CD45RA, CD45RO and CD31 subpopulations were evaluated in some centres. For 36 (18 PTI, 18 CT) children, immunophenotyping was performed and cell-associated HIV-1 DNA analysed on stored samples to 48 weeks. RESULTS: In the PTI group, CD4 cell count fell rapidly in the first 12 weeks off ART, with decreases in both naive and memory cells. However, the proportion of CD4 cells expressing CD45RA and CD45RO remained constant in both groups. The increase in CD8 cells in the first 12 weeks off ART in the PTI group was predominantly due to increases in RO-expressing cells. PTI was associated with a rapid and sustained increase in CD4 cells expressing Ki67 and HLA-DR, and increased levels of HIV-1 DNA. CONCLUSIONS: PTI in children is associated with rapid changes in CD4 and CD8 cells, likely due to increased cell turnover and immune activation. However, children off treatment may be able to maintain stable levels of naive CD4 cells, at least in proportion to the memory cell pool, which may in part explain the observed excellent CD4 cell recovery with re-introduction of ART.
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- 2013
11. Plasma drug concentrations and virologic evaluations after stopping treatment with nonnucleoside reverse-transcriptase inhibitors in HIV type 1-infected children
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Cressey, Tr, Green, H, Khoo, S, Treluyer, Jm, Compagnucci, A, Saidi, Y, Lallemant, M, Gibb, Dm, Burger, Dm, Collaborators: Aboulker JP, Paediatric European Network for Treatment of AIDS II Study G. r. o. u. p., Babiker, A, Blanche, S, Bohlin, Ab, Butler, K, Castelli Gattinara, G, Clayden, P, Darbyshire, Jh, Debré, M, de Groot, R, della Negra, M, Duicelescu, D, Giaquinto, C, Grosch Wörner, I, Kind, C, Levy, J, Lyall, H, Marczynska, M, Mellado Peña MJ, Nadal, D, Niehues, T, Peckham, C, Ramos Amador JT, Rosado, L, Rudin, C, Scherpbier, Hj, Sharland, M, Stevanovic, M, Tovo, Pier Angelo, Tudor Williams, G, Valerius, N, Walker, As, Wintergerst, U, Aboulker, Jp, Harper, L, Klein, N, Mofenson, L, Moye, J, Saïdi, Y, Jacqz Aigrain, E, Tréluyer, Jm, Clerici, M, De Rossi, A, Ngo Giang Huong, N, Muñoz Fernandez MA, Pillay, D, Hill, C, Lepage, P, Pozniak, A, Vella, S, Eliette, V, Hadjou, G, Léonardo, S, Pitrou, C, Riault, Y, Buck, L, Farrelly, L, Johnson, D, Taylor, C, Chalermpantmetagul, S, Peongjakta, R, Chailert, S, Fregonese, F, Jourdain, G, Butler, D, Carlton, C, Collins, D, Kao, G, Van Buskirk, S, Watson, S, Corradini, S, Floret, D, Laplace, J, Monpoux, F, Cottalorda, J, Lefebvre, Jc, Mellul, S, Boudjoudi, N, Firtion, G, Faye, A, Beniken, D, Damond, F, Tricoire, J, Krivine, A, Chaix, Ml, Notheis, G, Strotmann, G, Schlieben, S, Rampon, O, Zanchetta, M, Rosso, R, Repeto, E, Vitale, F, Martino, A, Bernardi, S, Mazza, A, Rossetti, G, Dobosz, S, Oldakowska, A, Popielska, J, Kaflik, M, Stanczak, J, Stanczac, T, González Tomé MI, Delgado García, R, José Mellado Peña, M, Martín Fontelos, P, Piñeiro Pérez, R, Alimenti, A, Penin, M, Gurbindo, D, Navarro Gomez ML, Jimenez, Jl, Prieto, C, de José Gómez MI, García Rodriguez MC, Moreno Pérez, D, Núñéz Cuadros, E, Asensi Botet, F, Pérez, A, Pérez Tamarit MD, Kalhert, C, Schupbach, J, Bunupuradah, T, Ananworanich, J, Phanuphak, P, Intasan, J, Ubolyam, S, Kanjanavanit, S, Namwong, T, Foster, C, Hamadache, D, Campbell, S, Hanley, C, Walsh, C, Kaye, S, Seery, P, Novelli, V, Shingadia, D, Flynn, J, Clapson, M, Jacobsen, M, Mcmaster, P, Hawkes, E, Liebeschuetz, S, Sodeinde, O, Wong, S, Walsh, S, Heath, Y, Weiner, L, Famiglietti, M, Rana, S, Yu, P, Roa, J, Puga, A, Haerry, A, Regazzi, M, Villani, S, Gibbons, S, Jullien, V, Rey, E, Treluye, Jm, Rodríguez Nóvoa, S, Tawon, Y., University of Zurich, and Green, H
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Cyclopropanes ,Male ,Time Factors ,Infectious diseases and international health [NCEBP 13] ,HIV Infections ,Drug resistance ,Pharmacology ,THERAPY ,PROPHYLAXIS ,2726 Microbiology (medical) ,chemistry.chemical_compound ,Plasma ,immune system diseases ,Medicine ,Child ,Reverse-transcriptase inhibitor ,RESISTANCE, THERAPY, EXPOSURE, PHARMACOGENETICS, PROPHYLAXIS ,virus diseases ,Drug holiday ,Viral Load ,Infectious Diseases ,Alkynes ,Child, Preschool ,Reverse Transcriptase Inhibitors ,Female ,Viral load ,medicine.drug ,Microbiology (medical) ,medicine.medical_specialty ,Efavirenz ,Nevirapine ,Adolescent ,CD4-CD8 Ratio ,610 Medicine & health ,Article ,Invasive mycoses and compromised host [N4i 2] ,Internal medicine ,Drug Resistance, Viral ,Humans ,Protease inhibitor (pharmacology) ,EXPOSURE ,PHARMACOGENETICS ,business.industry ,Poverty-related infectious diseases [N4i 3] ,2725 Infectious Diseases ,Benzoxazines ,CD4 Lymphocyte Count ,Regimen ,chemistry ,Withholding Treatment ,10036 Medical Clinic ,Mutation ,HIV-1 ,Microbial pathogenesis and host defense [UMCN 4.1] ,business ,RESISTANCE - Abstract
Contains fulltext : 71467.pdf (Publisher’s version ) (Open Access) BACKGROUND: The optimum strategy for stopping treatment with drugs that have different half-lives in a combination regimen to minimize the risk of selecting drug-resistant viruses remains unknown. We evaluated drug concentrations in plasma, human immunodeficiency virus (HIV) load, and development of drug resistance after a planned treatment interruption of a nonnucleoside reverse-transcriptase inhibitor (NNRTI)-containing regimen in HIV type 1-infected children. METHODS: Children with viral loads or =30% (for children aged 2-6 years) or CD4 cell percentages > or =25% and CD4 cell counts > or =500 cells/microL (for children aged 7-15 years) were randomized to either a planned treatment interruption or to continuous therapy. In the planned treatment interruption arm, either (1) treatment with nevirapine or efavirenz was stopped, and treatment with the remaining drugs was continued for 7-14 days, or (2) nevirapine or efavirenz were replaced by a protease inhibitor, and all drugs were stopped after 7-14 days. Sampling for determination of plasma drug concentrations, measurement of viral load, and drug resistance testing was scheduled at day 0, day 7 (drug concentrations only), day 14, and day 28 after interruption of treatment with an NNRTI. RESULTS: Treatment with an NNRTI was interrupted for 35 children (20 were receiving nevirapine, and 15 were receiving efavirenz). Median time from NNRTI cessation to stopping all drugs was 9 days (range, 6-15 days) for nevirapine and 14 days (range, 6-18 days) for efavirenz. At 7 days, 1 (5%) of 19 and 4 (50%) of 8 children had detectable nevirapine and efavirenz concentrations, respectively; efavirenz remained detectable in 3 (25%) of 12 children at 14 days. At 14 days, viral load was > or =50 copies/mL in 6 of 16 children interrupting treatment with nevirapine (range, 52-7000 copies/mL) and in 2 of 12 children interrupting treatment with efavirenz (range, 120-1600 copies/mL). No new NNRTI mutations were observed. CONCLUSIONS: In children with virological suppression who experienced interruption of treatment with an NNRTI, staggered or replacement stopping strategies for a median of 9 days for nevirapine and 14 days for efavirenz were not associated with the selection of NNRTI resistance mutations.
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- 2008
12. Dynamics of progression markers in a non-study population of human immunodeficiency virus-1 vertically infected infants with different antiretroviral treatments.
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Resino, S, Bellón, J M, Gurbindo, D, Ramos, J T, León, J A, Muñóz-Fernández, M Á, Bellón, J M, León, J A, and Muñóz-Fernández, M A
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HIV infections ,NEONATAL infections ,ANTIVIRAL agents - Abstract
Unlabelled: Treatment with highly active antiretroviral therapy (HAART) has been shown to modify viral replication dynamics and lead to a significant recovery of CD4+ T-cells. A retrospective multicentre observational study was performed in a non-study population of 151 HIV-1-infected children, categorized into four groups according to therapy: untreated (NT), on monotherapy (MT) with a nucleoside inhibitor, on combination therapy (CT) with two nucleoside inhibitors, and on HAART, protease inhibitor containing regimens, to assess the "real-life" effectiveness of these different therapies on plasma viral load (VL) and CD4+ T-cells. VL was quantified using a standard molecular assay. CD4+ and CD8+ T-cells subsets were determined by flow cytometry. The HAART group showed the highest relative proportion (RP) of increases in 5, 10, 15 and 20% of CD4+ T-cells over baseline, and the earliest fall-off of VL (0.5, 1, 1.5 and 2 log10 copies ml-1). The RP of the fall-off of 0.5, 1, 1.5 and 2 log10 VL below baseline was 3-fold higher in HAART group than in the MT and CT groups. However, no differences were found among the groups of treated children in reaching undetectable VL.Conclusion: A better evolution of VL and CD4+ T-cells was evident in children on HAART, indicating a positive effect on the immune system and clinical status, inhibiting HIV-1 replication and enabling the recovery of CD4+ T-cell counts. [ABSTRACT FROM AUTHOR]- Published
- 2002
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13. Disruption in cytokine and chemokine production by T-cells in vertically HIV-1-infected children.
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Resino, S, Bellón, J M, Gurbindo, D, Muñoz-Fernández, M A, Bellón, J M, and Muñoz-Fernández, M A
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T cells ,CYTOKINES ,CHEMOKINES - Abstract
Unlabelled: This study measured cytokine production by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) from 55 human immunodeficiency virus (HIV)-infected children born to HIV-infected mothers, and compared it with vertically exposed but uninfected age-matched children. A significant defect was observed in Th1 cytokine production [interferon-gamma and interleukin-2 (IL-2)] in HIV-infected children compared with controls, but without a concomitant increase in Th2 cytokines. Indeed, IL-5 and IL-10 production was even lower in HIV-infected children than in controls, with the decrease in IL-5 being the best predictive marker of immunodeficiency. In addition, an increased release of tumour necrosis factor-alpha (TNF-alpha) that correlated well with CD4+ levels, and a positive correlation of the TNF-alpha/IL-10 ratio with disease progression was observed. A correlation between AIDS-free status and higher %CD4+ and %CD8+ T-lymphocytes and RANTES (regulated on activation, normal T-cell expressed and secreted) production was also found.Conclusion: A dysfunctional cytokine production of PBMCs was observed in HIV-infected children in both Th1 and Th2 cytokines due to quantitative and qualitative defects induced by HIV-1. An important observation was an increased RANTES production associated with viral isolates of NSI/R5 phenotype and S/L kinetics. [ABSTRACT FROM AUTHOR]- Published
- 2001
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14. Naïve and memory CD4[sup +] T cells and T cell activation markers in HIV-1 infected children on HAART.
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Resino, S., Navarro, J., Bellón, J. M., Gurbindo, D., León, J. A., and Muñoz-Fernández, M. A.
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T cells ,AIDS in children ,BLOOD cells ,IMMUNOLOGY - Abstract
The objective of this study was to investigate the relationship between peripheral blood CD4[sup +] T cell subsets and routine viro-immunological markers in vertically HIV-1-infected children undergoing highly active antiretroviral therapy (HAART). CD4[sup +] and CD8[sup +] T cell subsets were examined by three-colour flow cytometry. Plasma viraemia was quantified by a standardized molecular assay. A negative correlation between the %CD4[sup +] T cells and both viral load and the %CD8[sup +] T cells was observed. A strong positive correlation between the %CD4 T cells and naïve, CD38[sup +] and non-activated CD4[sup +] T cell subsets was found, whereas the %CD4 T cells correlated negatively with the numbers of memory, activated and memory-activated CD4[sup +] T cell subsets. Elevated percentages of CD8 T cells were associated with increased memory and CD4[sup +] CD62L-T cell subsets, whereas the naïve and CD4[sup +] HLA-DR[sup ]CD38[sup +] subsets negatively correlated with the CD8%. Co-expression of CD62L on memory CD4[sup +] cells and high expression of HLA-DR (but not of CD38) were associated with high viral load. No association between viral load and naïve CD4[sup +] T cells was observed. Specific CD4[sup +] T cell subsets may be more informative than routine surrogate markers in defining the evolution of HIV infection and immune reconstitution in children. [ABSTRACT FROM AUTHOR]
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- 2001
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15. Correlation of Viral Load and CD8 T-Lymphocytes with Development of Neurological Manifestations in Vertically HIV-1-Infected Infants. A Prospective Longitudinal Study.
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Gurbindo, D., Resino, S., S�nchez-Ram�n, S., Le�n, J. A., and Mu�oz-Fern�ndez, M. A.
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- 1999
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16. IgD antibodies: in vitro blocking activity of IgE mediated reactions.
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BRINGEL, H., VELA, C., URENA, V., GURBINDO, D., GARCIA, R., and LAHOZ, C.
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- 1982
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17. Low blood CD8+ T-lymphocytes and high circulating monocytes are predictors of HIV-1-associated progressive encephalopathy in children.
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Sánchez-Ramón S, Bellón JM, Resino S, Cantó-Nogués C, Gurbindo D, Ramos J, and Muñoz-Fernández MA
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- 2003
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18. Multicenter study for the evaluation of the antibody response against salmonella typhi Vi vaccination (EMPATHY) for the diagnosis of Anti-polysaccharide antibody production deficiency in patients with primary immunodeficiency.
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Sánchez-Ramón S, de Gracia J, García-Alonso AM, Rodríguez Molina JJ, Melero J, de Andrés A, García Ruiz de Morales JM, Ferreira A, Ocejo-Vinyals JG, Cid JJ, García Martínez JM, Lasheras T, Vargas ML, Gil-Herrera J, García Rodríguez MC, Castañer JL, González Granado LI, Allende LM, Soler-Palacin P, Herráiz L, López Hoyos M, Bellón JM, Silva G, Gurbindo DM, Carbone J, Rodríguez-Sáinz C, Matamoros N, Parker AR, and Fernández-Cruz E
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- Adult, Agammaglobulinemia immunology, Aged, Common Variable Immunodeficiency immunology, Enzyme-Linked Immunosorbent Assay, Female, Host-Pathogen Interactions drug effects, Host-Pathogen Interactions immunology, Humans, Immunoglobulin G immunology, Male, Middle Aged, Prospective Studies, Salmonella typhi physiology, Typhoid Fever immunology, Typhoid Fever microbiology, Typhoid Fever prevention & control, Typhoid-Paratyphoid Vaccines administration & dosage, Vaccination methods, Young Adult, Antibodies, Bacterial immunology, Antibody Formation immunology, Immunologic Deficiency Syndromes immunology, Polysaccharides, Bacterial immunology, Salmonella typhi immunology, Typhoid-Paratyphoid Vaccines immunology
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- 2016
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19. Low thymic output, peripheral homeostasis deregulation, and hastened regulatory T cells differentiation in children with 22q11.2 deletion syndrome.
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Ferrando-Martínez S, Lorente R, Gurbindo D, De José MI, Leal M, Muñoz-Fernández MA, and Correa-Rocha R
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- Cell Differentiation, Child, Preschool, Female, Humans, Infant, Male, DiGeorge Syndrome immunology, DiGeorge Syndrome physiopathology, Homeostasis, T-Lymphocytes, Regulatory cytology, Thymus Gland physiopathology
- Abstract
Objective: To perform an extensive analysis of the immune status of asymptomatic children with the 22q11.2 deletion syndrome, with special emphasis on the regulatory T cells (Treg) population., Study Design: Analysis of thymic function, frequency and absolute counts of immune subsets, and phenotype of Treg were performed in 10 asymptomatic children bearing the 22q11.2 deletion and compared with 12 age-matched, healthy children., Results: Children with 22q11.2 deletion syndrome showed a curtailed thymic output, lower T-cell levels, and a homeostatic deregulation in the CD4 T-cell compartment, characterized by a greater proliferative history in the naïve CD4 T-cell subset. Treg numbers were markedly reduced in children with 22q11.2 deletion syndrome, and remaining Treg showed mostly an activated phenotype., Conclusions: Reduced thymic output in children with 22q11.2 deletion syndrome could be related with an increased proliferation in the naïve CD4 T-cell compartment and the consequent Treg activation to ensure that T-cell expansion remains under control. Deregulated peripheral homeostasis and loss of suppressive capacity by Treg could compromise the integrity of T-cell immunity during adulthood and play a relevant role in the increased incidence of autoimmune diseases reported in patients with the 22q11.2 deletion syndrome., (Copyright © 2014 Mosby, Inc. All rights reserved.)
- Published
- 2014
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20. Rate of candidiasis among HIV-infected children in Spain in the era of highly active antiretroviral therapy (1997-2008).
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Álvaro-Meca A, Jensen J, Micheloud D, Díaz A, Gurbindo D, and Resino S
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- Antiretroviral Therapy, Highly Active, Child, Child, Preschool, Female, HIV Infections drug therapy, Hospitalization statistics & numerical data, Humans, Infant, Male, Poisson Distribution, Spain epidemiology, Candidiasis epidemiology, Candidiasis virology, HIV Infections epidemiology, HIV Infections microbiology
- Abstract
Background: Candidiasis is the most common opportunistic infection seen in human immunodeficiency virus (HIV)-infected individuals. The aim of our study was to estimate the candidiasis rate and evaluate its trend in HIV-infected children in Spain during the era of highly active antiretroviral therapy (HAART) compared to HIV-uninfected children., Methods: We carried out a retrospective study. Data were obtained from the records of the Minimum Basic Data Set from hospitals in Spain. All HIV-infected children were under 17 years of age, and a group of HIV-uninfected children with hospital admissions matching the study group by gender and age were randomly selected. The follow-up period (1997-2008) was divided into three calendar periods: a) From 1997 to 1999 for early-period HAART; b) from 2000 to 2002 for mid-period HAART; and c) from 2003 to 2008 for late-period HAART., Results: Among children with hospital admissions, HIV-infected children had much higher values than HIV-uninfected children during each of the three calendar periods for overall candidiasis rates (150.0 versus 6.1 events per 1,000 child hospital admissions/year (p < 0.001), 90.3 versus 3.1 (p < 0.001), and 79.3 versus 10.7 (p < 0.001), respectively) and for non-invasive Candida mycosis (ICM) rates (118.5 versus 3.8 (p < 0.001), 85.3 versus 2.3 (p < 0.001), and 80.6 versus 6.0 (p < 0.001), respectively). In addition, HIV-infected children also had higher values of ICM rates than HIV-uninfected children, except during the last calendar period when no significant difference was found (32.4 versus 1.2 (p < 0.001), 11.6 versus 0.4 (p < 0.001), and 4.6 versus 2.3 (p = 0.387), respectively). For all children living with HIV/AIDS, the overall candidiasis rate (events per 1,000 HIV-infected children/year) decreased from 1997-1999 to 2000-2002 (18.8 to 10.6; p < 0.001) and from 2000-2002 to 2003-2008 (10.6 to 5.7; p = 0.060). Within each category of candidiasis, both non-ICM and ICM rates experienced significant decreases from 1997-1999 to 2003-2008 (15.9 to 5.7 (p < 0.001) and 4.1 to 0.3 (p < 0.001), respectively)., Conclusions: Although the candidiasis rate still remains higher than in the general population (from 1997 to 2008), candidiasis diagnoses have decreased among HIV-infected children throughout the HAART era, and it has ceased to be a major health problem among children with HIV infection.
- Published
- 2013
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21. Preterm neonates show marked leukopenia and lymphopenia that are associated with increased regulatory T-cell values and diminished IL-7.
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Correa-Rocha R, Pérez A, Lorente R, Ferrando-Martínez S, Leal M, Gurbindo D, and Muñoz-Fernández MÁ
- Subjects
- Humans, Infant, Newborn, Lymphocyte Subsets, Infant, Premature, Interleukin-7 blood, Leukopenia diagnosis, Lymphopenia diagnosis, T-Lymphocytes, Regulatory immunology
- Abstract
Introduction: Current advances in neonatology have improved survival among preterm and low-birth-weight infants. However, the risk of neonatal death in preterm infants is much greater than in full-term neonates and is frequently associated with infections., Methods: Little is known about the immune status of preterm neonates; therefore, we analyzed the frequency and absolute counts of different immune populations in 211 cord blood samples taken from very-preterm to full-term neonates., Results: We found that absolute counts of all the immune subsets analyzed (i.e., monocytes, granulocytes, B cells, natural killer (NK) cells, CD4(+), and CD8(+) T cells) were markedly lower in preterm infants than in full-term infants. Surprisingly, we observed that regulatory T cells (Tregs) were the only cell subset that did not decrease in preterm infants, and their frequency was even higher than in full-term infants., Discussion: Tregs are crucial to maternal-fetal tolerance, but their suppressive role could be also implicated in the leukopenia observed in preterm infants. We did not observe differences in thymic function, but we found that plasma levels of interleukin (IL)-7 and the frequency of its receptor were significantly decreased in preterm infants. Our results could help to identify leukopenia and to implement immune therapies that significantly diminish mortality in preterm neonates.
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- 2012
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22. A leaky mutation in CD3D differentially affects αβ and γδ T cells and leads to a Tαβ-Tγδ+B+NK+ human SCID.
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Gil J, Busto EM, Garcillán B, Chean C, García-Rodríguez MC, Díaz-Alderete A, Navarro J, Reiné J, Mencía A, Gurbindo D, Beléndez C, Gordillo I, Duchniewicz M, Höhne K, García-Sánchez F, Fernández-Cruz E, López-Granados E, Schamel WW, Moreno-Pelayo MA, Recio MJ, and Regueiro JR
- Subjects
- Animals, B-Lymphocytes immunology, Base Sequence, DNA Mutational Analysis, Female, Humans, Infant, Killer Cells, Natural immunology, Male, Mice, Pedigree, RNA Splice Sites genetics, Receptors, Antigen, T-Cell, alpha-beta metabolism, Receptors, Antigen, T-Cell, gamma-delta metabolism, Severe Combined Immunodeficiency etiology, CD3 Complex genetics, Mutation, Severe Combined Immunodeficiency genetics, Severe Combined Immunodeficiency immunology, T-Lymphocyte Subsets immunology
- Abstract
T cells recognize antigens via their cell surface TCR and are classified as either αβ or γδ depending on the variable chains in their TCR, α and β or γ and δ, respectively. Both αβ and γδ TCRs also contain several invariant chains, including CD3δ, which support surface TCR expression and transduce the TCR signal. Mutations in variable chains would be expected to affect a single T cell lineage, while mutations in the invariant chains would affect all T cells. Consistent with this, all CD3δ-deficient patients described to date showed a complete block in T cell development. However, CD3δ-KO mice have an αβ T cell-specific defect. Here, we report 2 unrelated cases of SCID with a selective block in αβ but not in γδ T cell development, associated with a new splicing mutation in the CD3D gene. The patients' T cells showed reduced CD3D transcripts, CD3δ proteins, surface TCR, and early TCR signaling. Their lymph nodes showed severe T cell depletion, recent thymus emigrants in peripheral blood were strongly decreased, and the scant αβ T cells were oligoclonal. T cell-dependent B cell functions were also impaired, despite the presence of normal B cell numbers. Strikingly, despite the specific loss of αβ T cells, surface TCR expression was more reduced in γδ than in αβ T cells. Analysis of individuals with this CD3D mutation thus demonstrates the contrasting CD3δ requirements for αβ versus γδ T cell development and TCR expression in humans and highlights the diagnostic and clinical relevance of studying both TCR isotypes when a T cell defect is suspected.
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- 2011
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23. Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome.
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Torrelo A, Patel S, Colmenero I, Gurbindo D, Lendínez F, Hernández A, López-Robledillo JC, Dadban A, Requena L, and Paller AS
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- Anemia, Hypochromic pathology, Child, Child, Preschool, Fatal Outcome, Female, Hepatomegaly pathology, Humans, Infant, Infant, Newborn, Inflammation pathology, Male, Sweet Syndrome diagnosis, Syndrome, Fever pathology, Lipodystrophy pathology, Skin Diseases pathology
- Abstract
Several syndromes manifest as recurrent daily fevers, skin lesions, and multisystem inflammation. We describe 4 patients with early-onset recurrent fevers, annular violaceous plaques, persistent violaceous eyelid swelling, low weight and height, lipodystrophy, hepatomegaly, and a range of visceral inflammatory manifestations. Laboratory abnormalities included chronic anemia, elevated acute-phase reactants, and raised liver enzymes. Histopathologic examination of lesional skin showed atypical mononuclear infiltrates of myeloid lineage and mature neutrophils. Our patients have a distinctive early-onset, chronic inflammatory condition with atypical or immature myeloid infiltrates in the skin. We propose the acronym CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) syndrome for this newly described disorder, which is probably genetic in origin., (Copyright 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)
- Published
- 2010
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24. Slow progression of human immunodeficiency virus and hepatitis C virus disease in a cohort of coinfected children.
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Micheloud D, Jensen J, Bellón JM, Gurbindo D, de José MI, Moreno D, Ramos JT, Muñoz-Fernández MA, and Resino S
- Subjects
- Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Child, Child, Preschool, Cohort Studies, Disease Progression, Female, HIV Infections complications, HIV Infections drug therapy, Hepacivirus, Hepatitis C complications, Humans, Infant, Male, Polymerase Chain Reaction, Spain, Viral Load, HIV, HIV Infections virology, Hepatitis C virology
- Abstract
We carried out a retrospective study to determine the evolution of 23 vertically HIV-1/HCV coinfected children and 30 vertically HIV-1 infected children (control group). Six out of 23 HIV-1/HCV coinfected children developed AIDS versus 20 out of 30 HIV-1 children (P < 0.05). HIV-1/HCV children had a good evolution in relation to CD4 and HIV-RNA viral load. They presented higher CD8 counts than HIV-1 children during long periods, and slower progression of HCV liver disease.
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- 2007
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25. Role of antiretroviral therapies in mucocutaneous manifestations in HIV-infected children over a period of two decades.
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Seoane Reula E, Bellon JM, Gurbindo D, and Muñoz-Fernandez MA
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- Antiretroviral Therapy, Highly Active methods, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, HIV Infections complications, HIV Infections immunology, HIV Seropositivity complications, HIV Seropositivity drug therapy, HIV Seropositivity immunology, HIV-1 immunology, Humans, Incidence, Lymphocyte Count, Phenotype, Prevalence, Retrospective Studies, Skin Diseases, Viral etiology, Skin Diseases, Viral pathology, Viral Load, Anti-Retroviral Agents therapeutic use, HIV Infections drug therapy, Skin Diseases, Viral prevention & control
- Abstract
Background: Human immunodeficiency virus (HIV) infection causes a severe cellular immunodeficiency, which results in a greater susceptibility to infectious, inflammatory and malignant conditions. Among these, pathologies of the skin seem to be those most frequently observed in HIV+ patients. However, there are few reports on how antiretroviral therapy affects skin disorders in HIV-infected children., Objective: To study the incidence and prevalence of skin disorders in a cohort of HIV-infected children, in relation to the antiviral therapy [nontreated, monotherapy, combined therapy and highly active antiretroviral therapy (HAART)] received, and their impact on immunological and virological markers. The treatments were those available in different calendar periods in the history of antiviral treatment., Materials and Methods: A retrospective, observational study in a cohort of 210 HIV-infected children was carried out. These children were followed up every 3 months throughout 22 years. The viral load (HIV RNA copies mL(-1)) was quantified using reverse transcriptase-polymerase chain reaction and the viral phenotype of HIV-1 isolates was determined by in vitro culture. T-lymphocyte subsets in peripheral blood were quantified by flow cytometry., Results: Mucocutaneous manifestations were diagnosed in 17% of the untreated infected children. Of the treated children in different treatment periods, 22% in the monotherapy period, 25% in the combined therapy period but only 10% on HAART had some type of mucocutaneous manifestation, concordant with a higher number of CD4+ T cells, a lower viral load and less cytopathic virus in the last group. Mucocutaneous manifestations of infectious aetiology were most frequently observed; they were detected in 13% of the children during the first calendar period (untreated children), 16% during the second and third periods (monotherapy and combined therapy) and only 5% in the last period (HAART). Interestingly, syncytium-inducing virus was present in 69% of all children with mucocutaneous manifestations of infectious aetiology., Conclusion: Only in the last calendar period (HAART) was a significant decrease observed in the prevalence of mucocutaneous manifestations with HIV infection associated with an increase in CD4+ T cells. In addition, we found a strong association between children who had mucocutaneous manifestations with an infectious aetiology and a more cytopathic (X4/SI) viral phenotype.
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- 2005
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26. Positive virological outcome after lopinavir/ritonavir salvage therapy in protease inhibitor-experienced HIV-1-infected children: a prospective cohort study.
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Resino S, Bellón JM, Ramos JT, Gonzalez-Rivera M, de José MI, González MI, Gurbindo D, Mellado MJ, Cabrero E, and Muñoz-Fernández MA
- Subjects
- Acquired Immunodeficiency Syndrome immunology, Acquired Immunodeficiency Syndrome virology, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Cohort Studies, Drug Therapy, Combination, Humans, Lopinavir, Prospective Studies, Pyrimidinones adverse effects, Ritonavir adverse effects, Salvage Therapy, Acquired Immunodeficiency Syndrome drug therapy, HIV-1, Pyrimidinones administration & dosage, Ritonavir administration & dosage
- Abstract
Background: Lopinavir/ritonavir has demonstrated antiviral activity in the HIV-infected patient., Objective: To analyse virological response to lopinavir/ritonavir therapy in previously protease inhibitor (PI)-experienced HIV-1-infected children., Materials and Methods: Sixty-seven HIV-1-children on lopinavir/ritonavir were studied in a multicentre prospective cohort observational study. The outcome variables were undetectable viral load (uVL; VL < or =400 copies/mL) and virological failure after uVL with a rebound of VL >400 copies/mL. VL and genotype of HIV-1-isolates were measured using standard assays., Results: 83.5% of children had a 1 log10 VL decrease including 65.6% who reached uVL. Children with >2 changes of antiretroviral therapy (ART) or >5 drugs needed a median time of 3-4 months higher than children with < or =2 changes of ART or < or =5 drugs previous to lopinavir/ritonavir, to reach those values, and the relative proportions (RP) were 2.2 (P =0.038) and 1.9 (P=0.050), respectively. Children with CD4+>15% (P=0.122), VL < or =30,000 (P < 0.001) copies/mL, and age >12 years (P=0.096) achieved an earlier control of VL during the follow-up. The children with virological failure or rebound of VL had higher baseline VL and lower CD4+ T-lymphocytes/mm3 and had taken a greater number of drugs previous to lopinavir/ritonavir. HIV-children with a new nucleoside reverse transcriptase inhibitor (NRTI), or protease inhibitor (PI) or PI plus non-nucleoside reverse transcriptase inhibitors (NNRTI) in the current regimen had a better virological response than children without these new drugs. Also, children with <6 protease mutations had an RP of 2.31 of achieving uVL., Conclusions: Highly active antiretroviral therapy (HAART) including lopinavir/ritonavir induces beneficial effects in terms of virological outcome responses, and it is an effective option for salvage therapy in PI-experienced HIV-1-infected children.
- Published
- 2004
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27. The effects on infants of potent antiretroviral therapy during pregnancy: a report from Spain.
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Bellón Cano JM, Sánchez-Ramón S, Ciria L, León JA, Gurbindo D, Fortuny C, Bertrán JM, Ruiz Contreras J, Ramos JT, Asensi O, Mur A, Resino R, and Muñóz-Fernández MA
- Subjects
- Anti-HIV Agents therapeutic use, Female, HIV Infections, HIV Seropositivity, HIV-1 metabolism, Humans, Infant, Newborn, Infectious Disease Transmission, Vertical, Pregnancy, Pregnancy Complications, Infectious, Pregnancy Outcome, Reverse Transcriptase Inhibitors therapeutic use, Spain, Time Factors, Anti-Retroviral Agents therapeutic use
- Abstract
Background: The purpose of our study was to assess the effects on infants of protease inhibitor (PI)-based antiretroviral therapy (ART) given to their HIV-positive mothers during pregnancy., Material/methods: A multicenter observational study was carried out at 11 centers in Spain, involving 124 HIV-1-infected pregnant women under ART and their infants. The mothers were classified according to the ART protocols used during pregnancy into two groups: group A, 52 women with > or =2 nucleoside reverse transcriptase inhibitors (NRTI) with or without NNRTI, for a mean time of 4.7+/-2.2 months; and group B, 72 women on protease inhibitor (PI)-based regimens for 5.4+/-2.6 months., Results: Maternal therapy was well tolerated, with no serious adverse effects on pregnancy course. No newborn was infected with HIV-1. There were two deaths at birth (group B), both with extreme prematurity. Among the 126 ART-exposed infants (4 siblings), the most common toxicity was anemia (29%), without significant differences between the two groups. Low birthweight and prematurity were also common (21% and 14%, respectively)., Conclusions: Optimal management of HIV-1 infection in women, regardless of their pregnancy status, can be recommended in more developed countries, without adverse effects on pregnancy outcome, and dramatically decreasing vertical transmission. HAART with PI versus potent ART during pregnancy was effective and safe for infants throughout the 12-month follow-up. In the light of recent advances in anti-HIV-1 pregnancy therapy, the long-term safety of these prophylactic and therapeutical strategies should be studied.
- Published
- 2004
28. Viral load and CD4+ T lymphocyte response to highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children: an observational study.
- Author
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Resino S, M Bellón J, Gurbindo D, Tomás Ramos J, Antonio León J, Jose Mellado M, and Angeles Muñoz-Fernández M
- Subjects
- Anti-HIV Agents adverse effects, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active, Child, HIV Infections drug therapy, HIV Infections virology, Humans, Regression Analysis, CD4-Positive T-Lymphocytes immunology, HIV Infections immunology, HIV-1 physiology, Viral Load
- Abstract
An observational study was performed involving 95 children with vertically transmitted human immunodeficiency virus type 1 infection to assess the sustainability of undetectable viral loads (VLs) and increased CD4+ T lymphocyte percentages after 48 months of highly active antiretroviral therapy (HAART). The median time to achieve a 10% increase in the CD4+ T lymphocyte percentage was 11.01 months. The median time to achieve an undetectable VL was 6.4 months. At the end of the study, 64.2% of the children had achieved an undetectable VL. Of the patients with an initial VL of >3.6 log10 copies/mL, 74.7% had a decrease in the VL of 1 log10 copies/mL. By contrast, of the patients who presented with an initial VL of >4.6 log10 copies/mL, 37.9% had a decrease of >2 log10 copies/mL. Higher VL at baseline, antiretroviral therapy regimens received before HAART, and multiple drug switches while receiving antiretroviral therapy were all inversely associated with an undetectable VL. A CD4+ T lymphocyte percentage of >25% was directly associated with undetectable VL during the follow-up period. In conclusion, first-line HAART induces beneficial virological and immunological outcome responses in children.
- Published
- 2003
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29. Neuroprotective effects of early antiretrovirals in vertical HIV infection.
- Author
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Sánchez-Ramón S, Resino S, Bellón Cano JM, Ramos JT, Gurbindo D, and Muñoz-Fernández A
- Subjects
- AIDS Dementia Complex drug therapy, Anti-Retroviral Agents pharmacology, Child, Child, Preschool, Female, HIV Infections drug therapy, HIV-1 drug effects, Humans, Infant, Male, Neuroprotective Agents pharmacology, Proportional Hazards Models, Retrospective Studies, Statistics, Nonparametric, Survival Analysis, Time Factors, AIDS Dementia Complex prevention & control, Anti-Retroviral Agents therapeutic use, HIV Infections prevention & control, Infectious Disease Transmission, Vertical prevention & control, Neuroprotective Agents therapeutic use
- Abstract
We performed a retrospective study of a series of 58 of 189 vertically HIV-1 infected children who went on to develop progressive HIV-1-associated encephalopathy to assess real-life effects of early antiretroviral therapy on neurologic outcome. Our findings clearly indicate that antiretroviral therapy before the onset of neurologic symptoms delayed presentation of progressive HIV-1-associated encephalopathy, with an additional beneficial effect on survival.
- Published
- 2003
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30. CD8+ T-cell numbers predict the response to antiviral therapy in HIV-1-infected children.
- Author
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Resino S, Bellón JM, Sánchez-Ramón S, Gurbindo D, León JA, and Muñoz-Fernández MA
- Subjects
- Adolescent, CD4-CD8 Ratio, CD4-Positive T-Lymphocytes metabolism, Child, Child, Preschool, Follow-Up Studies, HIV Infections blood, Humans, Infant, Longitudinal Studies, Lymphocyte Count, Predictive Value of Tests, Prospective Studies, T-Lymphocyte Subsets metabolism, Viral Load, Antiretroviral Therapy, Highly Active methods, CD8-Positive T-Lymphocytes metabolism, HIV Infections drug therapy, HIV-1 isolation & purification
- Abstract
Our objective was to study the probability of achieving undetectable viral load levels in HIV-1-infected children after 36 mo of highly active antiretroviral therapy (HAART). A prospective, multicenter, longitudinal study in 41 HIV-1-infected children on HAART was undertaken. Viral load was quantified using standard molecular assay. CD4+ and CD8+ T cell subsets were determined by flow cytometry. The probability of achieving undetectable viral load was determined using Kaplan-Meier curves according to groups by percentage CD8+ at baseline (CD8+ <25% or >25%). Lower baseline CD8+ T cell levels conditioned a less effective virological response to HAART in children, independent of baseline CD4+ T cell numbers and viral load levels. A greater number of children (81%) from CD8+ >25% group than from the CD8+ <25% (40%) presented undetectable viral load levels (p = 0.013). Additionally, the CD8+ >25% group showed a 4.5-fold higher (95% confidence interval: 1.1-19.2) relative proportion for achieving viral load <400 copies/mL than the CD8+ <25% group (p = 0.039). We concluded that monitoring CD8+ T cell numbers may be valuable in deciding when to start HAART in vertically HIV-1-infected children.
- Published
- 2003
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31. Association of CD8+ T lymphocyte subsets with the most commonly used markers to monitor HIV type 1 infection in children treated with highly active antiretroviral therapy.
- Author
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Navarro J, Resino S, Bellón JM, Abad ML, Gurbindo D, Fernández-Cruz E, and Muñóz-Fernández MA
- Subjects
- ADP-ribosyl Cyclase, ADP-ribosyl Cyclase 1, Adolescent, Antigens, Differentiation immunology, Antiretroviral Therapy, Highly Active, Biomarkers, CD4-Positive T-Lymphocytes immunology, CD57 Antigens immunology, Child, Child, Preschool, Cross-Sectional Studies, HIV Infections drug therapy, Humans, L-Selectin immunology, Leukocyte Common Antigens immunology, Membrane Glycoproteins, NAD+ Nucleosidase immunology, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Viral Load, Antigens, CD immunology, CD8-Positive T-Lymphocytes immunology, HIV Infections immunology, HIV-1 immunology, T-Lymphocyte Subsets immunology
- Abstract
In contrast to adults, there is no information about children concerning the effects of the new antiretroviral therapy on the chronic activation and expansion of CD8+ T cells. We have investigated the relationship between blood CD8(+) T cell subsets, with percent CD4+ cells (%CD4), percent CD8+ cells (%CD8), and plasma viral load (VL), in 39 vertically HIV-1-infected children receiving highly active antiretroviral therapy (HAART) (mean age, 7.6 years; range, 2-15.6 years). CD8+ subsets were examined by three-color multiparametric flow cytometry, and VL was quantified by standard assays. There was a strong positive correlation between activated CD8+ T cells and VL. An increase in memory and memory-activated CD8+ T cells correlated with increased VL, whereas nonactivated memory cells and CD28+ CD8+ T cells correlated negatively with VL. Naive and effector cells did not correlate with VL, although the CD8+ CD45RA -CD62L- subset correlated with increased VL. Activated CD8(+) T cells did not correlate with %CD4, but an increase in memory-activated and effector CD8+ T cells was associated with lower %CD4. Increased naive CD8+ and CD28 +CD8+ T cells showed a positive correlation with %CD4 and a negative correlation with %CD8. In conclusion, in HIV-1-infected children receiving HAART, the activation of CD8+ T cells is associated with high VL, whereas CD8 +CD28+ and nonactivated CD8+ memory cells are associated with lower viral load. Naive CD8+ and CD28 +CD8+ T cells are associated with an improved immunological status.
- Published
- 2001
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32. Predictive markers of clinical outcome in vertically HIV-1-infected infants. A prospective longitudinal study.
- Author
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Resino S, Gurbindo D, Cano JM, Sanchez-Ramón S, and Muõz-Fernández MA
- Subjects
- CD4 Lymphocyte Count, CD8-Positive T-Lymphocytes immunology, Female, HIV-1 isolation & purification, Humans, Infant, Newborn, Longitudinal Studies, Male, Predictive Value of Tests, Prospective Studies, Treatment Outcome, Viral Load, Biomarkers, HIV Infections immunology, Infectious Disease Transmission, Vertical
- Abstract
We have investigated the relationship between disease progression and several immunologic and virologic markers of HIV infection. Plasma samples from infants born to HIV-1-infected mothers were collected at birth and at 1, 2, 4, 6, 9, 12, 15, and 18 mo of age and subsequently were assayed every 6 mo for viral load, viral phenotype, and lymphocyte populations. A cutoff level of 25% indicative of a preserved immunologic status, both of CD4+ and CD8+ blood T cells, was associated with significant differences in disease progression (p = 0.04 and 0.02, respectively). Infants with median CD4+ T cells <25% had a relative risk of progression to AIDS 3.35-fold higher than those with CD4+ above this level (p = 0.05). The relative risk of progression to AIDS for infants with median CD8+ <25% was 4.95-fold higher than for those with CD8+ percent above this threshold (p = 0.03). Similarly, a cutoff level of viral load of 5.5 log10 copies/mL was indicative of a worse prognosis. Infants with median viral load >5.5 log10 copies/mL had a relative risk of progression to AIDS 23.72-fold higher (p = 0.0001) than those with median viral load below this threshold. Interestingly, changes from a slow replication and low titer to a rapid replication and high titer of virus and from nonsyncytium-inducing to syncytium-inducing viral phenotype were indicative of progression to AIDS. Our results indicate that biologic phenotype of viral isolates and CD8+ T-lymphocyte percentages in peripheral blood as well as viral load and CD4+ T-lymphocyte percentages could predict rapid progression to advanced HIV-1 disease in HIV-1-infected infants.
- Published
- 2000
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33. Adenoidal tissue mass as a clinical guide of disease evolution in vertically HIV-1 infected children.
- Author
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Benito MB, Sampelayo TH, Gurbindo D, Sánchez-Ramón BS, Gómez EM, and Muñoz-Fernández MA
- Subjects
- Adenoids pathology, Adolescent, Child, Child, Preschool, Disease Progression, HIV Infections diagnostic imaging, HIV Infections immunology, Humans, Hypertrophy, Infant, Nasopharynx diagnostic imaging, Radiography, T-Lymphocyte Subsets, Adenoids diagnostic imaging, HIV Infections diagnosis, HIV-1
- Abstract
Introduction: it is known that in early-stage HIV-induced disease there is a discrepancy between the levels of viral burden and virus replication in peripheral blood versus lymphoid organs. HIV disease is active in the lymphoid tissue throughout the period of clinical latency. However, it is not known how long term progression of HIV infection is influenced by short-term changes in the adenoidal size., Objective: To assess the reliability of adenoidal-nasopharyngeal (AN) ratio in predicting clinical evolution of pediatric HIV infection., Methods: lateral radiographs of the nasopharynx in 94 Caucasian children born to HIV-1-infected mothers ranged from 6 months to 15 years (60 children infected with HIV-1 and 34 without HIV infection), and in a control group of 692 normal children were evaluated to obtain the AN ratio in order to identify the relationship of AN profiles with different stages of the disease. Patients were rated regarding their clinical and immunological status according to the Center for Disease Control Classification., Results: statistically significant differences between the groups of HIV-1-infected children, seroreverters and controls in the AN ratio were found (P < 0.001). Moreover, significant differences were also found in individual children that correlated with clinical progression., Conclusion: examination of radiographic changes in adenoidal size by AN ratio in relation to clinical status during one year period in the whole group showed strong prognostic value. These findings may have important implications in the design of therapeutic strategies.
- Published
- 1999
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34. Immune reconstitution after in utero bone marrow transplantation in a fetus with severe combined immunodeficiency with natural killer cells.
- Author
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Gil J, Porta F, Bartolomé J, Lafranchi A, Verardi R, Notarangelo LD, Carlo-Stella C, Rodríguez R, Rodríguez JJ, Gurbindo D, Cela E, Zucca A, Fernández-Cruz E, and Ugazio AG
- Subjects
- Cesarean Section, Female, Fetal Blood immunology, Fetus, Humans, Infant, Newborn, Lymphocyte Activation, Male, Pregnancy, Prenatal Diagnosis, T-Lymphocytes immunology, Bone Marrow Transplantation methods, Killer Cells, Natural immunology, Severe Combined Immunodeficiency embryology, Severe Combined Immunodeficiency therapy
- Published
- 1999
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35. Microsporidiosis in HIV-positive children in Madrid (Spain).
- Author
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Del Aguila C, Navajas R, Gurbindo D, Ramos JT, Mellado MJ, Fenoy S, Muñoz Fernandez MA, Subirats M, Ruiz J, and Pieniazek NJ
- Subjects
- AIDS-Related Opportunistic Infections diagnosis, AIDS-Related Opportunistic Infections parasitology, Adolescent, Animals, Blastocystis isolation & purification, Child, Child, Preschool, Cryptosporidium isolation & purification, DNA, Protozoan analysis, Diarrhea parasitology, Feces parasitology, Female, Giardia isolation & purification, Humans, Infant, Infant, Newborn, Intestinal Diseases, Parasitic diagnosis, Intestinal Diseases, Parasitic parasitology, Male, Microsporida isolation & purification, Microsporidiosis diagnosis, Microsporidiosis parasitology, Polymerase Chain Reaction methods, Prevalence, Prospective Studies, Spain, AIDS-Related Opportunistic Infections epidemiology, Intestinal Diseases, Parasitic epidemiology, Microsporidiosis epidemiology
- Abstract
A prospective study was carried out to determine the prevalence rates of microsporidiosis and other enteroparasites in HIV-positive children in the Madrid area. HIV-positive pediatric patients from three hospitals were enrolled in the study. A total of 293 samples (158 stool and 127 urine) were collected from 83 children whose mean age was 6.3 years and had a mean CD4 count of 504.7/mm3 (range 1-2,220/mm3), 48 of whom suffered diarrhea at the time of the study. Microsporidia identification was investigated in stool and urine samples using Weber's chromotrope-based stain, IIF and PCR species-specific tests. Enteric parasites were identified in 32.5% of the children. Cryptosporidium sp. was the most common parasite encountered (14.4%), followed by Blastocytis sp. (9.6%) and Giardia duodenalis (8.4%). Microsporidia was only found in the stools of one child (1.2% of total and 2% of those with diarrhea) and Enterocytozoon bieneusi was demonstrated by PCR. The patient was 10 years old, presented non-chronic diarrhea and his CD4 count was 298/mm3. These data differ from those previously reported by us in HIV-positive adults (13.9%) in the same area, although this group showed more severely depressed CD4 lymphocyte counts than children. New epidemiological studies should be carried out to elucidate whether additional risk factors exist between these groups.
- Published
- 1997
- Full Text
- View/download PDF
36. Autoimmune phenomena in children with human immunodeficiency virus infection and acquired immunodeficiency syndrome.
- Author
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Rodríguez-Mahou M, López-Longo J, Lapointe N, Carreño L, Grau R, Gurbindo D, and Fernández-Cruz E
- Subjects
- Acquired Immunodeficiency Syndrome blood, Acquired Immunodeficiency Syndrome genetics, Acquired Immunodeficiency Syndrome immunology, Antibodies, Antinuclear blood, Antibodies, Antinuclear immunology, Autoantibodies blood, Case-Control Studies, Child, Child, Preschool, Follow-Up Studies, HIV Infections blood, HIV Infections genetics, Humans, Infant, Isoantibodies blood, Isoantibodies immunology, Polymerase Chain Reaction, Ribonucleoproteins, Small Nuclear blood, Ribonucleoproteins, Small Nuclear immunology, Autoantibodies immunology, Autoimmunity, DNA, Viral analysis, HIV Infections immunology, HIV-1
- Abstract
We have studied sera from 44 children with Human Immunodeficiency Virus infection and Acquired Immunodeficiency Syndrome using immunoblotting, radioimmunoassay, enzymoimmunoassay and indirect immunofluorescence. We have detected a low incidence of antinuclear (2.9%), anti-reticulin (2.9%) and anti-smooth muscle (14.7%) antibodies by indirect immunofluorescence. By enzymoimmunoassay we have detected anti-dsDNA (20.5%) and anti-ENA [anti-nRNP (61.3%), anti-Sm (29.5%), anti-Ro (47.7%) and anti-La (18.1%)] antibodies. Tests for anti-dsDNA by radioimmunoassay were negative, suggesting the presence of low-avidity anti-DNA antibodies. By immunoblotting we have detected anti-C (nRNP) (33.3%), anti-BB' (Sm) (33.3%), anti-Ro (60 KD) (4.5%) and anti-La (11.3%) antibodies. The presence of anti-Ro antibodies was associated with progressive neurological disease. Long-term follow-up studies with larger numbers of patients are necessary to evaluate the clinical significance of the presence of anti-dsDNA and anti-ENA antibodies in children infected with Human Immunodeficiency Virus.
- Published
- 1994
- Full Text
- View/download PDF
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