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1.
N Engl J Med ; 378(16): 1479-1493, 2018 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-29669226

RESUMEN

BACKGROUND: Donor availability and transplantation-related risks limit the broad use of allogeneic hematopoietic-cell transplantation in patients with transfusion-dependent ß-thalassemia. After previously establishing that lentiviral transfer of a marked ß-globin (ßA-T87Q) gene could substitute for long-term red-cell transfusions in a patient with ß-thalassemia, we wanted to evaluate the safety and efficacy of such gene therapy in patients with transfusion-dependent ß-thalassemia. METHODS: In two phase 1-2 studies, we obtained mobilized autologous CD34+ cells from 22 patients (12 to 35 years of age) with transfusion-dependent ß-thalassemia and transduced the cells ex vivo with LentiGlobin BB305 vector, which encodes adult hemoglobin (HbA) with a T87Q amino acid substitution (HbAT87Q). The cells were then reinfused after the patients had undergone myeloablative busulfan conditioning. We subsequently monitored adverse events, vector integration, and levels of replication-competent lentivirus. Efficacy assessments included levels of total hemoglobin and HbAT87Q, transfusion requirements, and average vector copy number. RESULTS: At a median of 26 months (range, 15 to 42) after infusion of the gene-modified cells, all but 1 of the 13 patients who had a non-ß0/ß0 genotype had stopped receiving red-cell transfusions; the levels of HbAT87Q ranged from 3.4 to 10.0 g per deciliter, and the levels of total hemoglobin ranged from 8.2 to 13.7 g per deciliter. Correction of biologic markers of dyserythropoiesis was achieved in evaluated patients with hemoglobin levels near normal ranges. In 9 patients with a ß0/ß0 genotype or two copies of the IVS1-110 mutation, the median annualized transfusion volume was decreased by 73%, and red-cell transfusions were discontinued in 3 patients. Treatment-related adverse events were typical of those associated with autologous stem-cell transplantation. No clonal dominance related to vector integration was observed. CONCLUSIONS: Gene therapy with autologous CD34+ cells transduced with the BB305 vector reduced or eliminated the need for long-term red-cell transfusions in 22 patients with severe ß-thalassemia without serious adverse events related to the drug product. (Funded by Bluebird Bio and others; HGB-204 and HGB-205 ClinicalTrials.gov numbers, NCT01745120 and NCT02151526 .).


Asunto(s)
Terapia Genética , Globinas beta/genética , Talasemia beta/terapia , Adolescente , Adulto , Antígenos CD34 , Niño , Transfusión de Eritrocitos/estadística & datos numéricos , Femenino , Técnicas de Transferencia de Gen , Vectores Genéticos , Hemoglobinas/análisis , Hemoglobinas/genética , Humanos , Lentivirus/genética , Masculino , Mutación , Trasplante Autólogo , Adulto Joven , Talasemia beta/genética
2.
Rev Infirm ; 70(274): 42-44, 2021 Oct.
Artículo en Francés | MEDLINE | ID: mdl-34565538

RESUMEN

Recent therapeutic innovations are significantly changing the management of young children with severe haemophilia. A team from the University Hospital of Nice (06) introduced emicizumab, the first subcutaneous non-replacement therapy. Integrated into the multi-professional management of children and their families, this innovative therapeutic option has shown encouraging initial results. Experience sharing.


Asunto(s)
Hemofilia A , Niño , Preescolar , Hemofilia A/terapia , Humanos
3.
Br J Haematol ; 177(5): 751-758, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28444729

RESUMEN

Childhood autoimmune haemolytic anaemia (AIHA) requires second-line immunosuppressive therapy in 30-50% of cases. It appears that rituximab is indicated in such circumstances. This prospective national study reports the practice, efficacy and tolerance of rituximab in children with isolated AIHA and AIHA in the setting of Evans syndrome (ES). Sixty-one children were given rituximab between 2000 and 2014. The median interval from diagnosis to rituximab was 9·9 [interquartile range (IQR) 1·6-28·5] months. Forty-six patients responded (75%) and the 6-year relapse-free survival (RFS) was 48%. Twenty patients relapsed at a median interval of 10·8 (IQR 3·9-18·7) months, rituximab allowed steroid withdrawal in 44/61 (72%) of children. In isolated AIHA, complete response and 6-year RFS were significantly higher than in ES (P < 0·05). Ten out of 61 patients were infants, seven of who responded with a 6-year RFS of 71%. Among patients without immunoglobulin substitution before rituximab, 4 are still receiving substitutions. Five patients died, including one potentially attributable to rituximab. This large observational series of childhood AIHA established the rituximab benefit-risk ratio, allowing steroid withdrawal, with 37% of long-term responders, mainly in isolated AIHA. All subgroups of patients drew benefit. Our long-term results indicate the baseline to be challenged by new treatment approaches.


Asunto(s)
Anemia Hemolítica Autoinmune/tratamiento farmacológico , Hematínicos/uso terapéutico , Rituximab/uso terapéutico , Adolescente , Transfusión Sanguínea/estadística & datos numéricos , Niño , Preescolar , Sustitución de Medicamentos , Femenino , Francia , Humanos , Masculino , Estudios Prospectivos , Esteroides/uso terapéutico , Resultado del Tratamiento
4.
J Allergy Clin Immunol ; 129(3): 770-7, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22153772

RESUMEN

BACKGROUND: Primary immunoglobulin deficiencies lead to recurrent bacterial infections of the respiratory tract and bronchiectasis, even with adequate immunoglobulin replacement therapy. It is not known whether patients able to secrete IgM (eg, those with hyper-IgM [HIgM] syndrome) are as susceptible to these infections as patients who lack IgM production (eg, those with panhypogammaglobulinemia [PHG]). OBJECTIVE: This study is aimed at identifying specific microbiological and clinical (infections) characteristics that distinguish immunoglobulin-substituted patients with PHG from patients with HIgM syndrome. METHODS: A cohort of patients with HIgM syndrome (n = 25) and a cohort of patients with PHG (n = 86) were monitored prospectively for 2 years while receiving similar polyvalent immunoglobulin replacement therapies. Regular bacterial analyses of nasal swabs and sputum were performed, and clinical events were recorded. In parallel, serum and saliva IgM antibody concentrations were measured. RESULTS: When compared with patients with PHG, patients with HIgM syndrome were found to have a significantly lower risk of nontypeable Haemophilus influenzae carriage in particular (relative risk, 0.39; 95% CI, 0.21-0.63). Moreover, patients with HIgM syndrome (including those unable to generate somatic hypermutations of immunoglobulin genes) displayed anti-nontypeable H influenzae IgM antibodies in their serum and saliva. Also, patients with HIgM syndrome had a lower incidence of acute respiratory tract infections. CONCLUSIONS: IgM antibodies appear to be microbiologically and clinically protective and might thus attenuate the infectious consequences of a lack of production of other immunoglobulin isotypes in patients with HIgM syndrome. Polyvalent IgG replacement therapy might not fully compensate for IgM deficiency. It might thus be worth adapting long-term antimicrobial prophylactic regimens according to the underlying B-cell immunodeficiency phenotype.


Asunto(s)
Agammaglobulinemia/inmunología , Anticuerpos Antivirales/metabolismo , Infecciones por Haemophilus/inmunología , Haemophilus influenzae/inmunología , Síndrome de Inmunodeficiencia con Hiper-IgM/inmunología , Inmunoglobulina M/metabolismo , Adolescente , Agammaglobulinemia/complicaciones , Agammaglobulinemia/epidemiología , Anticuerpos Antivirales/inmunología , Niño , Femenino , Infecciones por Haemophilus/complicaciones , Infecciones por Haemophilus/epidemiología , Haemophilus influenzae/patogenicidad , Humanos , Síndrome de Inmunodeficiencia con Hiper-IgM/complicaciones , Síndrome de Inmunodeficiencia con Hiper-IgM/epidemiología , Inmunoglobulina M/inmunología , Incidencia , Masculino , Estudios Prospectivos , Sistema Respiratorio/inmunología , Sistema Respiratorio/patología , Sistema Respiratorio/virología , Riesgo
5.
Nat Med ; 28(1): 81-88, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35075288

RESUMEN

Sickle cell disease (SCD) and transfusion-dependent ß-thalassemia (TDT) are the most prevalent monogenic disorders worldwide. Trial HGB-205 ( NCT02151526 ) aimed at evaluating gene therapy by autologous CD34+ cells transduced ex vivo with lentiviral vector BB305 that encodes the anti-sickling ßA-T87Q-globin expressed in the erythroid lineage. HGB-205 is a phase 1/2, open-label, single-arm, non-randomized interventional study of 2-year duration at a single center, followed by observation in long-term follow-up studies LTF-303 ( NCT02633943 ) and LTF-307 ( NCT04628585 ) for TDT and SCD, respectively. Inclusion and exclusion criteria were similar to those for allogeneic transplantation but restricted to patients lacking geno-identical, histocompatible donors. Four patients with TDT and three patients with SCD, ages 13-21 years, were treated after busulfan myeloablation 4.6-7.9 years ago, with a median follow-up of 4.5 years. Key primary endpoints included mortality, engraftment, replication-competent lentivirus and clonal dominance. No adverse events related to the drug product were observed. Clinical remission and remediation of biological hallmarks of the disease have been sustained in two of the three patients with SCD, and frequency of transfusions was reduced in the third. The patients with TDT are all transfusion free with improvement of dyserythropoiesis and iron overload.


Asunto(s)
Anemia de Células Falciformes/terapia , Terapia Genética , Lentivirus/genética , Talasemia beta/terapia , Adolescente , Femenino , Terapia Genética/efectos adversos , Humanos , Masculino , Resultado del Tratamiento , Adulto Joven
6.
Arch Pediatr ; 28(1): 101-103, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33250331

RESUMEN

Beta thalassemias are autosomal recessive hemoglobin disorders related to a defect in the beta-globin chain production. Most of the major forms of beta-thalassemia are transfusion dependent leading to iron overload. Today, three iron chelators are available in France. We report the case of a patient suffering from ß+ major transfusion-dependent thalassemia who presented with severe skin reactions to deferoxamine and deferasirox as well as with agranulocytosis after deferiprone administration. The patient benefited from successful tolerance induction to deferasirox. With the increasing number of children suffering from iron overload, we believe that our protocol can be useful to pediatric hematology teams confronted with multiple iron chelator reactions.


Asunto(s)
Deferasirox/efectos adversos , Desensibilización Inmunológica/métodos , Erupciones por Medicamentos/terapia , Quelantes del Hierro/efectos adversos , Talasemia beta/tratamiento farmacológico , Preescolar , Deferasirox/uso terapéutico , Erupciones por Medicamentos/etiología , Humanos , Tolerancia Inmunológica , Lactante , Quelantes del Hierro/uso terapéutico , Talasemia beta/inmunología
7.
J Pediatr Gastroenterol Nutr ; 49(5): 599-606, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19668009

RESUMEN

OBJECTIVES: : Progressive liver injury is a concern in HIV-infected children exposed to long-term antiretroviral drugs and to the cytopathic effect of HIV. Yet liver biopsy is usually considered too invasive to be repeated in these patients. The aims of this study are to evaluate the feasibility of noninvasive hepatic investigations in HIV-1-infected children, assess the prevalence of signs of liver affection, and analyse the influence of the HIV disease severity and the exposure to antiretroviral therapy. MATERIALS AND METHODS: : A cross-sectional study conducted in 26 HIV-1 vertically infected children ages 8 to 18 years old. Liver function was assessed with standard serum biochemical markers, FibroTest, ActiTest, SteatoTest, Forns index, aspartate aminotransferase to platelet ratio index, ultrasound, and Fibroscan. RESULTS: : Nineteen (>60%) children had signs of liver affection on at least 1 of the test results: 13 (50%) had elevated liver enzymes, 15 (63%), 8 (33%), 5 (21%), and 5 (21%) had abnormal FibroTest, ActiTest, Forns index, and aspartate aminotransferase to platelet ratio index results, respectively. Four children (17%) had mild liver steatosis on ultrasound. Fibroscan measures were significantly higher in patients than in age-matched healthy children. Patients with elevated Fibroscan measures also had significantly higher FibroTest results. Age, HIV stage N in the Centers for Disease Control and Prevention classification and exposure duration to nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor drugs were the main risk factors for hepatotoxicity. CONCLUSIONS: : More than half of our population of HIV-infected children had biological and/or radiological signs of liver affection. Regular follow-up of liver function is necessary in these patients, which is now possible with noninvasive procedures.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Hígado Graso/etiología , Infecciones por VIH/complicaciones , VIH-1 , Hígado/patología , Inhibidores de la Transcriptasa Inversa/efectos adversos , Adolescente , Factores de Edad , Terapia Antirretroviral Altamente Activa/efectos adversos , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Plaquetas , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Niño , Estudios Transversales , Progresión de la Enfermedad , Hígado Graso/epidemiología , Estudios de Factibilidad , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/enzimología , Infecciones por VIH/patología , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Hígado/enzimología , Masculino
8.
BMJ Open ; 8(7): e022409, 2018 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-30049701

RESUMEN

INTRODUCTION: Severe haemophilia is a rare disease characterised by spontaneous bleeding from early childhood, which may lead to various complications, especially in joints. It is nowadays possible to avoid these complications thanks to substitutive therapies for which the issue of adherence is major. The transition from adolescence to adulthood in young people with severe haemophilia is a critical period as it is associated with a high risk of lack of adherence to healthcare, which might have serious consequences on daily activities and on quality of life. METHODS AND ANALYSIS: We present the protocol for a cross-sectional, observational, multicentric study to assess the differences between adolescents and young adults with severe haemophilia in France through the transition process, especially on adherence to healthcare. This study is based on a mixed methods design, with two complementary and consecutive phases, comparing data from a group of adolescents (aged 14-17 years) with those from a group of young adults (aged 20-29 years). The quantitative phase focuses on the determinants (medical, organisational, sociodemographic and social and psychosocial and behavioural factors) of adherence to healthcare (considered as a marker of the success of transition). The qualitative phase explores participants' views in more depth to explain and refine the results from the quantitative phase. Eligible patients are contacted by the various Haemophilia Treatment Centres participating in the French national registry FranceCoag. ETHICS AND DISSEMINATION: The study was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2016-A01034-47). Study findings will be disseminated to the scientific and medical community in peer-reviewed journals and presented at scientific meetings. Results will be popularised to be communicated via the French association for people with haemophilia to participants and to the general public. TRIAL REGISTRATION NUMBER: NCT02866526; Pre-results.


Asunto(s)
Hemofilia A/terapia , Transición a la Atención de Adultos , Cumplimiento y Adherencia al Tratamiento/estadística & datos numéricos , Rendimiento Académico , Adolescente , Adulto , Actitud Frente a la Salud , Estudios Transversales , Relaciones Familiares , Femenino , Francia , Hemofilia A/psicología , Humanos , Masculino , Satisfacción del Paciente , Factores Protectores , Investigación Cualitativa , Calidad de Vida , Factores de Riesgo , Clase Social , Cumplimiento y Adherencia al Tratamiento/psicología , Adulto Joven
9.
Clin Infect Dis ; 45(6): 785-94, 2007 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-17712765

RESUMEN

BACKGROUND: Some children who are infected with human immunodeficiency virus type 1 (HIV-1) during the perinatal period remain asymptomatic for very long periods in the absence of antiretroviral treatment, as is the case for some adults. Our objective was to estimate the proportion of children who developed neither symptoms nor major immunological perturbations to the age of > or = 10 years in a prospective cohort of infected children who had been observed since birth. METHODS: The ongoing prospective French Pediatric Cohort includes 568 HIV-1-infected children. Here, we report the follow-up data for all 348 HIV-1-infected children who were born before 1 January 1994. Children with long-term nonprogression of infection (LTNPs) were defined as HIV-1-infected children who had been observed for at least 10 years, never received antiretroviral treatment other than zidovudine monotherapy, never developed symptoms of Centers for Disease Control and Prevention clinical category C or B, and had a CD4+ cell percentage of < 25% no more than once during follow-up. Other definitions were compared. RESULTS: The Kaplan-Meier estimate of long-term nonprogression was 2.4% (95% confidence interval, 1.1%-4.6%) at 10 years of age, and 7 children were classified as LTNPs. The Kaplan-Meier estimates decreased slightly with age, to 1.8% at 12 years of age and 1.4% at 14 years of age. Plasma HIV-1 replication rates were low (< 1000 copies RNA/mL) for 2 of the 7 LTNPs at the age of 10 years (0.6% of the total denominator). None of the routinely measured maternal or perinatal markers were significantly linked to long-term nonprogression, with the exception of the mother's Centers for Disease Control and Prevention clinical category at the time of delivery. CONCLUSIONS: Approximately 2% of children who were infected during the perinatal period displayed no immunological or clinical progression by the age of 10 years. This figure is close to that reported for adults in studies that have used similar definitions.


Asunto(s)
Infecciones por VIH/patología , VIH-1 , Adolescente , Fármacos Anti-VIH/uso terapéutico , Niño , Preescolar , Estudios de Cohortes , Progresión de la Enfermedad , Estudios de Seguimiento , Francia/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Lactante , Estimación de Kaplan-Meier , Factores de Tiempo , Zidovudina/uso terapéutico
10.
Haematologica ; 92(12): 1691-4, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18055994

RESUMEN

The safety and efficacy of rituximab have been retrospectively assessed in 17 children with Evans syndrome. Patients received 4 or 3 weekly doses of rituximab (375 mg/m(2) per dose) associated with prednisone, alone (14 patients) or associated with other immunosuppressive drugs. Complete or partial remission of at least one cytopenia was achieved in 13 out of the 17 patients (76%), and lasted in 11 of them with a mean follow-up of 2.4 years (range 0.5-7 years). Steroid therapy was stopped or tapered at 50-100% of the baseline dosage in all long-term responders. Moderate side effects and infection occurred only in 4 and 1 children respectively.


Asunto(s)
Anemia Hemolítica Autoinmune/tratamiento farmacológico , Anticuerpos Monoclonales/administración & dosificación , Factores Inmunológicos/administración & dosificación , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Adolescente , Anemia Hemolítica Autoinmune/complicaciones , Anemia Hemolítica Autoinmune/mortalidad , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales de Origen Murino , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Francia , Humanos , Factores Inmunológicos/efectos adversos , Lactante , Infecciones/inducido químicamente , Infecciones/mortalidad , Masculino , Prednisolona/administración & dosificación , Prednisolona/efectos adversos , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/mortalidad , Sistema de Registros , Inducción de Remisión , Rituximab , Tasa de Supervivencia , Síndrome
11.
AIDS ; 18(18): 2401-9, 2004 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-15622316

RESUMEN

OBJECTIVE: To assess both benefits and risks related to treatment interruption (TI) in children with chronic HIV-1 materno-fetal infection. DESIGN: : A multicentre, retrospective analysis in five university hospital pediatric departments in France. METHODS: Clinical events, plasma HIV-1 RNA, CD4 cell counts, CD4 percentages (CD4%) and genotypes were recorded in 24 patients before and during TI. Patients were classified as sparing regimen or virological failure groups according to the main reason for treatment interruption. Clinical events, immuno-virological evolution and genotype reversions were monitored. RESULTS: After a median of 40 weeks of TI, none of the patients presented with an AIDS-defining event. For the whole cohort, median viral load variation from baseline, measured during TI was +1.26 log10 copies/ml (range, -0.22, +4.3 log10) with large inter-individual variability, median absolute CD4 cell loss was 32.5% (range, -82, +17%). These variations were not different in the two patient groups. The mean number of mutations conferring resistance to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors at baseline and last evaluation did not differ significantly. Few mutation reversions to wild type were noted in our cohort. CONCLUSIONS: Treatment interruption in children with chronic HIV-1 infection is associated with higher viral load increases than observed in adult patients. The CD4 cell loss is comparable. Although no clinical AIDS-defining event was noted close monitoring is required when TI is proposed to HIV-infected children. Very few reversion mutations were observed during treatment interruption.


Asunto(s)
Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Privación de Tratamiento , Adolescente , Recuento de Linfocito CD4 , Niño , Preescolar , Enfermedad Crónica , Femenino , Genotipo , Infecciones por VIH/genética , Humanos , Masculino , Mutación/genética , ARN Viral/sangre , Estudios Retrospectivos , Factores de Riesgo , Insuficiencia del Tratamiento
12.
Clin Infect Dis ; 39(11): 1692-8, 2004 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-15578372

RESUMEN

BACKGROUND: The clinical impact of early antiretroviral multidrug therapy on the risk of early-onset severe human immunodeficiency virus (HIV) disease has not been evaluated on a large scale. METHODS: We evaluated the risk of early-onset events associated with acquired immunodeficiency syndrome (AIDS), particularly the risk of encephalopathy, among infants in the French Perinatal Cohort, according to whether antiretroviral multidrug therapy was initiated before or after the age of 6 months. RESULTS: Of 83 HIV-infected infants born in 1996 (when HAART became available) or later, 40 received early treatment on or before the age of 6 months, and 43 received deferred multidrug therapy after the age of 6 months. In the group that received early multidrug therapy, no child developed an opportunistic infection or an encephalopathy during the first 24 months of life. In the deferred multidrug therapy group, 6 infants presented with a total of 7 AIDS-associated events (P=.01), 3 of which were encephalopathies (P=.08). The small number of events prevented the identification of clinical and biological markers that accurately predict progression of early-onset severe HIV disease. CONCLUSION: In this observational study, infants who received multidrug therapy before 6 months of age did not have the early-onset severe form of childhood HIV disease. Further studies are needed to find accurate early markers of disease progression in this age group.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Progresión de la Enfermedad , Quimioterapia Combinada , Infecciones por VIH/epidemiología , Humanos , Lactante , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Factores de Tiempo
13.
Pediatr Infect Dis J ; 21(6): 518-25, 2002 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12182375

RESUMEN

BACKGROUND: To assess tolerance and efficacy of early multitherapy including a protease inhibitor for infants perinatally infected with HIV. METHODS: Observational study of tolerance and clinical and immunovirologic evolution in HIV-infected infants treated before the age of 1 year in the French Perinatal Study. RESULTS: Thirty-one infants were included. The median age was 3.7 months at initiation of multitherapy. Clinical stage was C (n = 8), B (n = 5) or A/N (n = 18). The median HIV RNA viral load was 5.8 log copies/ml, and the median CD4 cell percentage was 29%. Median follow-up of treatment was 27 months. Of 31 infants 15 experienced mild to moderate adverse events. No infant had clinical or immunologic progression. The median change in viral load was -2.7 log copies/ml after 3 months, -2.0 log after 12 months and -1.7 log after 24 months of treatment. The proportion of infants with a viral load below 500 copies/ml decreased from 53% at 6 months to 18% at 24 months of treatment. The virologic response was not correlated with viral load at baseline. However, the slope of the viral load decrease during the first month of treatment was predictive of the virologic response at 3 and 6 months. Fourteen infants with a viral load of >500 copies/ml after 6 months of treatment displayed viruses with antiretroviral resistance mutations in reverse transcriptase and/or protease genes. CONCLUSIONS: Despite the absence of clinical or immunologic progression, the high frequency of virologic failure associated with genotypic resistance reveals the difficulties associated with implementing antiretroviral multitherapy in infants. Suboptimal doses of protease inhibitor could be a factor contributing to treatment failure.


Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/efectos de los fármacos , Quimioterapia Combinada , Endopeptidasas/genética , Infecciones por VIH/inmunología , Infecciones por VIH/prevención & control , Transcriptasa Inversa del VIH/genética , VIH-1/inmunología , Humanos , Lactante , Recién Nacido , Mutación , ARN Viral/análisis , ARN Viral/sangre , Medición de Riesgo
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