RESUMEN
BACKGROUND: Reports of long-term tenofovir disoproxil fumarate (TDF) treatment in HIV-infected adolescents are limited. We present final results from the open-label (OL) TDF extension following the randomized, placebo (PBO)-controlled, double-blind phase of GS-US-104-0321 (Study 321). METHODS: HIV-infected 12- to 17-year-olds treated with TDF 300 mg or PBO with an optimized background regimen (OBR) for 24-48 weeks subsequently received OL TDF plus OBR in a single arm study extension. HIV-1 RNA and safety, including bone mineral density (BMD), was assessed in all TDF recipients. RESULTS: Eighty-one subjects received TDF (median duration 96 weeks). No subject died or discontinued OL TDF for safety/tolerability. At week 144, proportions with HIV-1 RNA <50 copies/mL were 30.4% (7 of 23 subjects with baseline HIV-1 RNA >1000 c/mL initially randomized to TDF), 41.7% (5 of 12 subjects with HIV-1 RNA <1000 c/mL who switched PBO to TDF) and 0% (0 of 2 subjects failed randomized PBO plus OBR with HIV-1 RNA >1000 c/mL and switched PBO to TDF). Viral resistance to TDF occurred in 1 subject. At week 144, median decrease in estimated glomerular filtration rate was 38.1 mL/min/1.73 m (n = 25). Increases in median spine (+12.70%, n = 26) and total body less head BMD (+4.32%, n = 26) and height-age adjusted Z-scores (n = 21; +0.457 for spine, +0.152 for total body less head) were observed at week 144. Five of 81 subjects (6%) had persistent >4% BMD decreases from baseline. CONCLUSIONS: Some subjects had virologic responses to TDF plus OBR, and TDF resistance was rare. TDF was well tolerated and can be considered for treatment of HIV-infected adolescents.
Asunto(s)
Adenina/análogos & derivados , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa/efectos adversos , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , Organofosfonatos/efectos adversos , Organofosfonatos/uso terapéutico , Adenina/efectos adversos , Adenina/uso terapéutico , Adolescente , Densidad Ósea , Niño , Método Doble Ciego , Farmacorresistencia Viral , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Humanos , Masculino , Placebos/administración & dosificación , ARN Viral/sangre , Tenofovir , Insuficiencia del Tratamiento , Carga ViralRESUMEN
Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) is one of the most serious complications associated with solid organ and hematopoietic stem cell transplantation. PTLD is most frequently seen with primary EBV infection post-transplant, a common scenario for pediatric solid organ recipients. Risk factors for infection or reactivation of EBV following solid organ transplant are stronger immunosuppressive therapy regimens, and being seronegative for receptor. For hematopoietic stem cell transplantation, the risk factors relate to the type of transplant, human leukocyte antigen disparity, the use of stronger immunosuppressants, T-cell depletion, and severe graft-versus-host disease. Mortality is high, and most frequent in patients who develop PTLD in the first six months post-transplant. The primary goal of this article is to provide an overview of the clinical manifestations, diagnosis, accepted therapies, and management of EBV infection in transplant recipients, and to suggest that the adoption of monitoring protocols could contribute to a reduction in related complications.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trastornos Linfoproliferativos/virología , Trasplante de Órganos/efectos adversos , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/prevención & control , Infecciones por Virus de Epstein-Barr/terapia , Humanos , Terapia de Inmunosupresión/métodos , Inmunosupresores/uso terapéutico , Factores de RiesgoRESUMEN
Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) is one of the most serious complications associated with solid organ and hematopoietic stem cell transplantation. PTLD is most frequently seen with primary EBV infection post-transplant, a common scenario for pediatric solid organ recipients. Risk factors for infection or reactivation of EBV following solid organ transplant are stronger immunosuppressive therapy regimens, and being seronegative for receptor. For hematopoietic stem cell transplantation, the risk factors relate to the type of transplant, human leukocyte antigen disparity, the use of stronger immunosuppressants, T-cell depletion, and severe graft-versus-host disease. Mortality is high, and most frequent in patients who develop PTLD in the first six months post-transplant. The primary goal of this article is to provide an overview of the clinical manifestations, diagnosis, accepted therapies, and management of EBV infection in transplant recipients, and to suggest that the adoption of monitoring protocols could contribute to a reduction in related complications.
Asunto(s)
Humanos , Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trastornos Linfoproliferativos/virología , Trasplante de Órganos/efectos adversos , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/prevención & control , Infecciones por Virus de Epstein-Barr/terapia , Terapia de Inmunosupresión/métodos , Inmunosupresores/uso terapéutico , Factores de RiesgoRESUMEN
BACKGROUND: To evaluate the long-term (up to week 292) safety, efficacy and tolerability of ritonavir-boosted tipranavir in HIV-1-infected pediatric patients. Long-term follow up of patients enrolled in the randomized, open-label pediatric trial (1182.14/PACTG1051). METHODS: HIV-1-infected pediatric patients (2-18 years) who participated in the PACTG 1051 trial were followed for ritonavir-boosted tipranavir-based regimen efficacy, safety and tolerability through week 292. RESULTS: In patients <12 years of age, 51/62 (82%) were receiving drug at week 48 and 13/62 (21%) at week 288. Among adolescents (12-18 years of age), 35/53 (66%) were receiving drug at week 48 and 2/53 (4%) at week 288. Among patients 2 to <6 years of age, 18/25 (72%) had viral loads <400 copies/mL at week 48. By week 292, 9/25 (36%) of patients had viral loads <400 copies/mL. Among older patients, week 48 responder rates were 35% (13/37 of patients 6 to <12 years of age) and 32% (17/53 of patients 12 to 18 years of age). By week 292, 6/37 (16%) of those 6 to <12 years of age and 2/53 (4%) of those 12 to 18 years of age had viral loads <400 copies/mL. Overall safety and tolerability profiles were best for children who initiated treatment between 2 and <6 years of age. Drug-related adverse events (investigator defined) were similar across all age groups (55-65%). CONCLUSIONS: Pediatric patients who begin treatment at the earlier ages, and who are stable on a ritonavir-boosted tipranavir-based regimen at week 48, generally continue to demonstrate good safety, tolerability and virologic efficacy profiles up to 292 weeks of treatment.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Piridinas/administración & dosificación , Pironas/administración & dosificación , Ritonavir/administración & dosificación , Adolescente , Fármacos Anti-VIH/efectos adversos , Niño , Preescolar , Combinación de Medicamentos , Infecciones por VIH/virología , Humanos , Piridinas/efectos adversos , Pironas/efectos adversos , Ritonavir/efectos adversos , Sulfonamidas , Carga ViralRESUMEN
BACKGROUND: There are few data on the safety and antiviral activity of tenofovir disoproxil fumarate (TDF) in HIV-1 infected adolescents. METHODS: A randomized, double-blinded, placebo-controlled study was conducted. Ninety adolescents (12 to <18 years) who were viremic while receiving antiretroviral treatment were randomized to receive TDF 300 mg (mean, 216.8 mg/m(2)) or placebo in combination with an optimized background regimen (OBR) for 48 weeks. The primary efficacy endpoint was time-weighted average change in plasma HIV-1 RNA from baseline at week 24 RESULTS: Eighty-seven subjects (45 TDF, 42 placebo) received the study drug. Through week 24, the median time-weighted average change in plasma HIV-1 RNA was not different between the TDF and placebo groups (-1.6 versus -1.6 log(10)copies/mL, P = 0.55). The percentages of subjects who achieved HIV-1 RNA <400 copies/mL were similar at week 24 (40.9 versus 41.5%). One fourth of subjects in the TDF and placebo groups (24.4 versus 28.6%) had at least 3 active agents in the OBR. Many subjects in both groups had baseline genotypic resistance to TDF (48.9 versus 33.3%). TDF was generally safe and well tolerated. There were no statistically significant differences in changes of renal function and bone mineral density between the 2 groups. CONCLUSION: This study of TDF in combination with an OBR in antiretroviral-experienced adolescents did not meet its primary or secondary efficacy endpoints. The effectiveness of the OBR and baseline genotypic resistance to TDF in both groups may have confounded the efficacy findings. No clinically relevant TDF-related renal or bone toxicities were observed in this adolescent population.
Asunto(s)
Adenina/análogos & derivados , Fármacos Anti-VIH , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Organofosfonatos , Inhibidores de la Transcriptasa Inversa , Adenina/administración & dosificación , Adenina/efectos adversos , Adenina/uso terapéutico , Adolescente , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Niño , Método Doble Ciego , Farmacorresistencia Viral , Quimioterapia Combinada , Femenino , Infecciones por VIH/virología , VIH-1/fisiología , Humanos , Masculino , Organofosfonatos/administración & dosificación , Organofosfonatos/efectos adversos , Organofosfonatos/uso terapéutico , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Tenofovir , Resultado del Tratamiento , Viremia/tratamiento farmacológico , Viremia/virologíaRESUMEN
The objective of this study was to estimate and analyze the costs of treating children with HIV/AIDS at a university hospital in São Paulo, Brazil. The study collected and analyzed data from 291 medical records of children treated at the hospital as of March 2002. The costs of treatment were estimated for each category of patient (exposed and infected) and severity, based on the quantity of inputs and procedures used in treating each child, based on the cost accounting system used at the hospital. The total cost of treatment for children exposed to the HIV was R$ 956.41 and for those infected with HIV R$ 8,092.71 per year. The mean cost of ambulatory care was R$ 6,047.28 for children with severe conditions, R$ 3,714.45 for those with light/moderate conditions, and R$ 948.63 for the exposed. Hospitalized children had annual costs of R$ 19,353.34, R$ 18,823.16, and R$ 871.03, respectively. The medication was a major factor in the cost of treatment. Our estimates are comparable to the findings from other studies, but lower than corresponding findings from the international literature.
Asunto(s)
Terapia Antirretroviral Altamente Activa/economía , Infecciones por VIH/economía , Costos de la Atención en Salud , Hospitalización/economía , Síndrome de Inmunodeficiencia Adquirida/economía , Atención Ambulatoria/economía , Brasil , Niño , Análisis Costo-Beneficio , Hospitales Universitarios/economía , Humanos , Índice de Severidad de la EnfermedadRESUMEN
The objective of this study was to estimate and analyze the costs of treating children with HIV/AIDS at a university hospital in São Paulo, Brazil. The study collected and analyzed data from 291 medical records of children treated at the hospital as of March 2002. The costs of treatment were estimated for each category of patient (exposed and infected) and severity, based on the quantity of inputs and procedures used in treating each child, based on the cost accounting system used at the hospital. The total cost of treatment for children exposed to the HIV was R$ 956.41 and for those infected with HIV R$ 8,092.71 per year. The mean cost of ambulatory care was R$ 6,047.28 for children with severe conditions, R$ 3,714.45 for those with light/moderate conditions, and R$ 948.63 for the exposed. Hospitalized children had annual costs of R$ 19,353.34, R$ 18,823.16, and R$ 871.03, respectively. The medication was a major factor in the cost of treatment. Our estimates are comparable to the findings from other studies, but lower than corresponding findings from the international literature.
O objetivo deste estudo foi estimar e analisar os custos de tratamento da criança com HIV/AIDS em um hospital universitário de São Paulo, Brasil. Foram analisados 291 prontuários de crianças expostas ou infectadas acompanhadas no Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, em março de 2002. O custo foi estimado por categoria de paciente (exposta e infectada) e nível de gravidade (graves e leves/moderados), com base na quantidade de procedimentos e insumos utilizados no tratamento, e valorizado monetariamente por meio do sistema de apuração de custos existente no Instituto da Criança. O custo total estimado de tratamento da criança exposta ao HIV foi de R$ 956,41 e da criança infectada de R$ 8.092,71 por ano. O custo do tratamento ambulatorial foi de R$ 6.047,28, R$ 3.714,45 e R$ 948,63, respectivamente para os pacientes infectados graves, leves/moderados e para as crianças expostas, e o custo médio de internação foi de R$ 19.353,34, R$ 18.823,16 e R$ 871,03, respectivamente. O custo foi fortemente influenciado pelo consumo de medicamentos e comparável aos obtidos pelos demais estudos publicados, embora inferior ao estimado em estudos internacionais.
Asunto(s)
Niño , Humanos , Terapia Antirretroviral Altamente Activa/economía , Costos de la Atención en Salud , Infecciones por VIH/economía , Hospitalización/economía , Síndrome de Inmunodeficiencia Adquirida/economía , Atención Ambulatoria/economía , Brasil , Análisis Costo-Beneficio , Hospitales Universitarios/economía , Índice de Severidad de la EnfermedadRESUMEN
Although treatment of children infected with HIV with protease inhibitors has improved the survival of these patients, various adverse side effects have been reported, including metabolic abnormalities, such as hyperlipidaemia. We describe a case of hip osteonecrosis in an adolescent with AIDS who was being treated with protease inhibitors. There is a possible relation with hyperlipidemia. F.M.G., white, 11 years old, AIDS A2, started to receive AZT and DDI when he was 7 years old. In April 1999, the patient had a significant increase in viral load and so the antiretroviral therapy was switched to d4T, 3TC and Ritonavir. Triglyceride plasma levels reached 460mg/dl after this switch and were always above the reference value. In December 1999, the patient complained of pain in the right hip. On physical examination, he had limited movement of this joint. Magnetic resonance imaging of the right hip showed flattening, deformity and fragmentation of the femoral head, compatible with osteonecrosis. Few cases of femoral head osteonecrosis have been associated with HIV infection, in the absence of the classic risk factors for osteonecrosis. Metabolic risk factors include hypertriglyceridaemia. The immunological disorders that occur in the HIV infection may predispose the patient to avascular osteonecrosis and metabolic disorders, particularly hypertriglyceridemia, while the use of protease inhibitors, may be considered an additional risk factor for osteonecrosis. Given the importance of premature diagnosis and to avoid complications of osteonecrosis, we recommend evaluation of musculoskeletal symptoms in children receiving protease inhibitors.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Necrosis de la Cabeza Femoral/complicaciones , Hiperlipidemias/complicaciones , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Analgésicos , Niño , Inhibidores de la Proteasa del VIH/efectos adversos , Humanos , Hiperlipidemias/inducido químicamente , MasculinoRESUMEN
Although treatment of children infected with HIV with protease inhibitors has improved the survival of these patients, various adverse side effects have been reported, including metabolic abnormalities, such as hyperlipidaemia. We describe a case of hip osteonecrosis in an adolescent with AIDS who was being treated with protease inhibitors. There is a possible relation with hyperlipidemia. F.M.G., white, 11 years old, AIDS A2, started to receive AZT and DDI when he was 7 years old. In April 1999, the patient had a significant increase in viral load and so the antiretroviral therapy was switched to d4T, 3TC and Ritonavir. Triglyceride plasma levels reached 460mg/dl after this switch and were always above the reference value. In December 1999, the patient complained of pain in the right hip. On physical examination, he had limited movement of this joint. Magnetic resonance imaging of the right hip showed flattening, deformity and fragmentation of the femoral head, compatible with osteonecrosis. Few cases of femoral head osteonecrosis have been associated with HIV infection, in the absence of the classic risk factors for osteonecrosis. Metabolic risk factors include hypertriglyceridaemia. The immunological disorders that occur in the HIV infection may predispose the patient to avascular osteonecrosis and metabolic disorders, particularly hypertriglyceridemia, while the use of protease inhibitors, may be considered an additional risk factor for osteonecrosis. Given the importance of premature diagnosis and to avoid complications of osteonecrosis, we recommend evaluation of musculoskeletal symptoms in children receiving protease inhibitors.
Asunto(s)
Niño , Humanos , Masculino , Hiperlipidemias , Necrosis de la Cabeza Femoral/complicaciones , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Analgésicos , Inhibidores de la Proteasa del VIH , Hiperlipidemias , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológicoRESUMEN
No presente trabalho sao registrados dois casos de aspergilose em criancas imunocomprometidas. O estudo micologico completo identificou Aspergillus flavus como agente de dois processos. A presenca cada vez mais frequente da aspergilose invasiva deve-se ao numero crescente de pacientes imunocomprometidos, muitos com hemopatias graves submetidos a quimioterapia. O diagnostico precoce em um dos casos possibilitou remissao do processo. Tratava-se de paciente com leucemia mieloide aguda, tendo sido isolado o fungo do sangue circulante. O segundo caso evoluiu para obito, com infeccao fungica generalizada.
Asunto(s)
Humanos , Femenino , Niño , Adolescente , Aspergilosis/diagnóstico , Leucemia Mieloide Aguda/complicaciones , Aspergilosis/inmunología , Aspergillus flavus/aislamiento & purificaciónRESUMEN
Os autores relatam o caso de uma criança do sexo feminino, de oito anos de idade, portadora de paracoccidioidomicose profunda, com febre intermitente, hepatomegalia, linfadenopatia abdominal, comprometimento do esqueleto com lesöes ósseas do tipo osteolítico, acompanhado de aumento das partes moles e cardiomegalia com derrame pericárdio, sem acometimento pulmonar
Asunto(s)
Humanos , Femenino , Niño , Diagnóstico por Imagen/métodos , Linfadenopatía Inmunoblástica/diagnóstico , Osteólisis Esencial/diagnóstico , ParacoccidioidomicosisRESUMEN
Propöe concepçöes fundamentais para a elaboraçäo de uma nova política de informaçöes em saúde: elaborar a política através de consensos construídos a partir de experiências; definir claramente os papéis institucionais e técnicos a níveis locais, estaduais e federais; usar abordagens interdisciplinares e intersetoriais; enfatizar o nível local; transformar a busca da qualidade das informaçöes produzidas como um processo contínuo (AMSB)