RESUMO
Kaposi sarcoma is a rare angioproliferative disease associated with human herpes virus-8 (HHV-8) infection. Kaposi sarcoma is frequent and aggressive in HIV-infected people, whereas the classic form (CKS) generally has an indolent course. Notably, all conventional therapies against Kaposi sarcoma have only temporary efficacy. We have previously shown that indinavir, a HIV protease-inhibitor with direct antiangiogenic and antitumor activity, is safe and effective in patients with early CKS, whereas effects are less prominent in advanced disease, probably due to the larger tumor mass. Therefore, the clinical response to indinavir was assessed in patients with advanced CKS after debulking chemotherapy. This was a monocentric phase 2 trial in elderly with progressive/advanced CKS treated with debulking chemotherapy and indinavir combined, followed by a maintenance phase with indinavir alone. Secondary endpoints included safety and Kaposi sarcoma biomarker evaluation.All evaluable patients (22) responded to debulking therapy. Out of these, 16 entered the indinavir maintenance phase. The overall response rate at end of maintenance was 75% (estimated median response-duration 43 months). Moreover, most responders showed further clinical improvements (lesion number/nodularity) during maintenance and post-treatment follow-up. Notably, after relapse, progressors did not require systemic Kaposi sarcoma therapy and showed clinical improvements (including disease stabilization) remaining on study. Responders also showed immune status amelioration with a consistent B-cell increase and positive changes of other biomarkers, including anti-HHV-8 natural killer activity. In advanced CKS a strategy combining indinavir and chemotherapy is safe and associated with high and durable response rates and it could be rapidly adopted for the clinical management of these patients. SIGNIFICANCE: This phase-2 trial showed that the HIV protease inhibitor indinavir may boost and extend the duration of the effects of chemotherapy in elderly with advanced progressive classic Kaposi sarcoma, without additional toxicity. Further, the amelioration of the immune status seen in responders suggests a better control of HHV-8 infection and tumor-cell killing. Thus, indinavir combined with chemotherapy may represent an important tool for the clinical management of classic Kaposi sarcoma in elderly patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Inibidores da Protease de HIV , Indinavir , Sarcoma de Kaposi , Humanos , Sarcoma de Kaposi/tratamento farmacológico , Indinavir/uso terapêutico , Indinavir/administração & dosagem , Indinavir/efeitos adversos , Masculino , Feminino , Idoso , Inibidores da Protease de HIV/uso terapêutico , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso de 80 Anos ou mais , Resultado do Tratamento , Herpesvirus Humano 8RESUMO
BACKGROUND: Study of liquid lopinavir/ritonavir (LPV/r) in young infants has been limited by concerns for its safety in neonates. METHODS: International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1106 was a phase IV, prospective, trial evaluating the safety and pharmacokinetics of antiretroviral medications administered according to local guidelines to South African preterm and term infants <3 months of age. Safety evaluation through 24-week follow-up included clinical, cardiac and laboratory assessments. Pharmacokinetic data from P1106 were combined with data from International Maternal Pediatric Adolescent AIDS Clinical Trials Network studies P1030 and P1083 in a population pharmacokinetics model used to simulate LPV exposures with a weight-band dosing regimen in infants through age 6 months. RESULTS: Safety and pharmacokinetics results were similar in 13/28 (46%) infants initiating LPV/r <42 weeks postmenstrual age (PMA) and in those starting ≥42 weeks PMA. LPV/r was started at a median (range) age of 47 (13-121) days. No grade 3 or higher adverse events were considered treatment related. Modeling and simulation predicted that for infants with gestational age ≥27 weeks who receive the weight-band dosing regimen, 82.6% will achieve LPV trough concentration above the target trough concentration of 1.0 µg/mL and 56.6% would exceed the observed adult lower limit of LPV exposure of 55.9 µg·h/mL through age 6 months. CONCLUSIONS: LPV/r oral solution was safely initiated in a relatively small sample size of infants ≥34 weeks PMA and >2 weeks of life. No serious drug-related safety signal was observed; however, adrenal function assessments were not performed. Weight-band dosing regimen in infants with gestational age ≥27 weeks is predicted to result in LPV exposures equivalent to those observed in other pediatric studies.
Assuntos
Inibidores da Protease de HIV , Lopinavir , Ritonavir , Humanos , Lactente , Recém-Nascido , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/farmacocinética , Lopinavir/efeitos adversos , Lopinavir/farmacocinética , Estudos Prospectivos , Ritonavir/efeitos adversos , Ritonavir/farmacocinética , Administração OralRESUMO
Resumen Introducción: El impacto del cambio de terapia antiretroviral (TAR) para tratar la dislipidemia en pacientes infectados por VIH no ha sido reportado en Chile. Objetivo: Evaluar la efectividad y seguridad a 12 meses del cambio de TAR a esquema con raltegravir (RAL) para tratar la dislipidemia. Material y Métodos: Cohorte retrospectiva de pacientes con infección por VIH en TAR, atendidos en Fundación Arriarán, con dislipidemia y que cambiaron a esquema con RAL para tratarla. Resultados: Se incluyó 73 casos, en TAR con inhibidores no nucleosídicos de transcriptasa reversa (INNTR; 50,7%) o inhibidores de proteasa (IP; 49,3%), con dislipidemia mixta (42,5%) o hipertrigliceridemia aislada (57,5%). La mediana de colesterol total (CT) y triglicéridos (TG) basales era 228 mg/dl y 420 mg/dl, respectivamente. El 94,5% tenía carga viral (CV) indetectable. Se modificó TAR de base en 58,4%; 89,1% recibía hipolipemiantes. Las concentraciones plasmáticas de lípidos descendieron significativamente a 12 meses (TG= −43,6%; CT= −19,3%). Ningún paciente presentó fracaso virológico, aunque 10,9% tuvo viremia detectable a 12 meses, mayoritariamente transitoria. Conclusiones: El cambio de TAR a RAL en pacientes dislipidémicos tratados con INNTR o IP reduce significativamente las concentraciones plasmáticas de TG y CT a 12 meses. Es una estrategia segura, pero puede observarse viremia transitoria.
Background: The impact of switching antiretroviral therapy (ART) regimen for dyslipidemia management in HIV-infected (HIV+) patients has not been reported in Chile. Aim: To assess effectiveness and safety at 12 months after switching to raltegravir-based regimen for dyslipidemia management. Methods: Retrospective cohort of HIV+ patients receiving ART at Arriaran Foundation, with dyslipidemia switched to raltegravir-based regimen for lipid management. Results: 73 patients were included, receiving ART based in nonnucleoside reverse transcriptase inhibitor (NNRTI; 50,7%) or protease inhibitor (PI; 49,3%), with mixed dyslipidemia (42,5%) or isolated hypertriglyceridemia (57,5%). At baseline, median total cholesterol (TC) and triglycerides (TG) were 228 mg/dl and 420 mg/dl, respectively; undetectable viral load (VL) was present in 94,5% of patients. Backbone ART was switched in 58,4% and lipid-lowering therapy was used by 89,1% of them. At 12 months, there was a significant decrease in TG (-43,6%) and TC (-19,3%). No cases of virologic failure were observed, although 10,9% of patients had detectable VL at 12 months, mostly transient. Conclusions: Switching ART to raltegravir-based regimen in dyslipidemic patients receiving NNRTI or PI is associated with a significative decrease in TG and TC at 12 months. This strategy is safe, but VL can be increased temporarily.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Dislipidemias/prevenção & controle , Raltegravir Potássico/administração & dosagem , Infecções por HIV/sangue , Estudos Retrospectivos , Estudos de Coortes , Seguimentos , Contagem de Linfócito CD4 , Carga ViralRESUMO
Contexto: A solicitação da exclusão dos antirretrovirais fosamprenavir (FPV) 700mg e didanosina entérica (ddI EC) 250mg e 400mg do arsenal terapêutico de antirretrovirais para tratamento do HIV/aids baseia-se na substituição desses fármacos por outros com melhor eficácia e posologia, além de menor toxicidade e menos interações medicamentosas, tendo como foco disponibilizar melhores opções de tratamento para as pessoas vivendo com HIV/aids (PVHA). Recomendação da CONITEC: Na reunião realizada no dia 30 de novembro de 2016, os membros presentes deliberaram por unanimidade recomendar a exclusão dos medicamentos antirretrovirais (ARV) na forma farmacêutica comprimido de fosamprevir (FPV) 700 mg, dianosina entérica ddI EC 250 mg e ddI EC 400 mg do arsenal terapêutico de antirretrovirais para o tratamento do HIV/aids. Recomendação da CONITEC: Na reunião realizada no dia 30 de novembro de 2016, os membros presentes deliberaram por unanimidade recomendar a exclusão dos medicamentos antirretrovirais (ARV) na forma farmacêutica comprimido de fosamprevir (FPV) 700 mg, dianosina entérica ddI EC 250 mg e ddI EC 400 mg do arsenal terapêutico de antirretrovirais para o tratamento do HIV/aids. Decisão: Excluir os medicamentos antirretrovirais (ARV) fosamprenavir (FPV) 700mg, didanosina entérica ddI EC 250mg e ddI EC 400mg do arsenal terapêutico de antirretrovirais para tratamentodo HIV/Aids, no âmbito do Sistema Único de Saúde SUS, dada pela Portaria SCTIE-MS nº 49 publicada no Diário Oficial da União (D.O.U.) nº 246, de 23 de dezembro de 2016.
Assuntos
Humanos , HIV , Didanosina/efeitos adversos , Didanosina/uso terapêutico , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/uso terapêutico , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Brasil , Análise Custo-Benefício , Falha de Tratamento , Substituição de MedicamentosAssuntos
Humanos , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/administração & dosagem , Ritonavir/administração & dosagem , Síndrome de Lipodistrofia Associada ao HIV/induzido quimicamente , Darunavir/administração & dosagem , Triglicerídeos/sangue , Estudos Prospectivos , Inibidores da Protease de HIV/efeitos adversos , Ritonavir/efeitos adversos , Síndrome de Lipodistrofia Associada ao HIV/sangue , Substituição de Medicamentos , Darunavir/efeitos adversos , LDL-Colesterol/sangueRESUMO
We report a 41-year-old man with HIV and a chronic obstructive pulmonary disease, treated for seven months with Fluticasone/Salmeterol and antiretroviral therapy (Lamivudine, Tenofovir, Atazanavir and Ritonavir). While using these medications, the patients developed a Cushing syndrome in a period of five months. After performing laboratory and imaging tests, it was concluded that the most probable cause of the syndrome was the interaction of inhaled steroids with Ritonavir. After discontinuing these medications the syndrome reverted in a period of 8 months.
Assuntos
Humanos , Masculino , Adulto , Broncodilatadores/efeitos adversos , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Síndrome de Cushing/induzido quimicamente , Xinafoato de Salmeterol/efeitos adversos , Fluticasona/efeitos adversos , Nebulizadores e Vaporizadores , Broncodilatadores/uso terapêutico , Inibidores da Protease de HIV/uso terapêutico , Síndrome de Cushing/diagnóstico , Interações Medicamentosas , Xinafoato de Salmeterol/uso terapêutico , Fluticasona/uso terapêuticoRESUMO
Abstract In this study, 275 patients in use of tenofovir were retrospectively followed-up for three years to evaluate risk factors involved in impaired renal function. Analysis of variance (ANOVA) and Tukey's test were used to verify any differences in creatinine levels and estimated clearance at 0, 6, 12, 24 and 36 months, adjusting for the co-variables sex, skin color, age >50 years, arterial hypertension, diabetes and the use of the ritonavir-boosted protease inhibitors (PI/r) lopinavir/r or atazanavir/r. The software package STATISTICA 10® was used for statistical analysis. The patients’ mean age was 43.2 ± 10.7 years. Systemic arterial hypertension (SAH) and diabetes were found in 20.4% and 8.7% of the patients, respectively. Overall, 96.7% were on tenofovir associated with lamivudine (TDF + 3TC), 39.3% on lopinavir/r, 29.8% on efavirenz, and 17.6% on atazanavir/r. There was a statistically significant difference in estimated creatinine clearance at 24 months, when the co-variables male (F = 3.95; p = 0.048), SAH (F = 6.964; p = 0.009), and age over 50 years (F = 45.81; p < 0.001) were taken into consideration. Analysis of the co-variable use of atazanavir/r showed a tendency toward an increased risk over time (F = 2.437; p = 0.063); however, no significant time interaction was seen. At 36-month, a statistically significant difference was found for age over 50 years, (F = 32.02; p < 0.05) and there was a significant time-by-sex interaction (F = 3.117; p = 0.0149). TDF was discontinued in 12 patients, one because of a femoral neck fracture (0.7%) and 11 due to nephrotoxicity (4%). Of these latter cases, 9/11 patients were also using protease inhibitors. These data strongly alert that tenofovir use should be individualized with careful attention to renal function especially in male patients, over 50 years, with SAH, and probably those on ATV/r.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Fármacos Anti-HIV/efeitos adversos , Rim/efeitos dos fármacos , Tenofovir/efeitos adversos , Fármacos Anti-HIV/administração & dosagem , Quimioterapia Combinada/efeitos adversos , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/efeitos adversos , Rim/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tenofovir/administração & dosagemRESUMO
El ergotismo es una complicación de la intoxicación aguda y/o el abuso crónico de los derivados del ergot. Se manifiesta por síndrome vasomotor con enfermedad vascular periférica que frecuentemente compromete extremidades. Presentamos cuatro casos de pacientes infectados con el virus de la inmunodeficiencia humana 1 (HIV-1), en tratamiento con antirretrovirales que incluyen inhibidores de la proteasa reforzados con ritonavir, y que habían recibido ergotamina como automedicación. Ellos desarrollaron síntomas de enfermedad vascular periférica y al examen físico sus pulsos estaban disminuidos o ausentes. El Doppler arterial confirmó signos de espasmo arterial difuso en dos de ellos. Se hizo diagnóstico de ergotismo secundario a la asociación de ergotamina-inhibidores de la proteasa. Los pacientes fueron tratados con la discontinuación de las drogas involucradas (inhibidores de la proteasa y ergotamina), bloqueantes cálcicos, profilaxis antitrombótica con enoxaparina, antiagregación con ácido acetil salicílico y uno ellos recibió pentoxifilina e infusión de prostaglandinas vasodilatadoras con mejoría de los síntomas. Discutimos la presentación clínica de esta interacción medicamentosa, difícil de diagnosticar correctamente sin una fuerte sospecha de su existencia.
Ergotism is a complication of acute intoxication and/or chronic abuse of ergot derivatives. It expresses itself through a vasomotor syndrome with peripheral vascular disease which frequently involves extremities. We report four cases of HIV-1 infected patients treated with antiretroviral drugs including boosted-protease inhibitors who had self-treated themselves with ergotamine. They developed peripheral vascular disease symptoms and their pulses where diminished or absent in the physical examination. Arterial Doppler confirmed diffused arterial spasm in two of them. Ergotism following ergotamine-protease inhibitors association was diagnosed. Patients were treated through the discontinuity of involved drugs (protease inhibitors and ergotamine), calcium blockers; antithrombotic prophylaxis with enoxaparine, antiaggregant therapy with acetylsalicylic acid, and one of them received pentoxifylline and vasodilator prostaglandins infusion, with amelioration of the symptoms. We discuss the clinical presentation of this drug interaction, difficult to diagnose properly without a strong suspicion of its existence.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Ergotamina/efeitos adversos , Ergotismo/etiologia , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Ritonavir/efeitos adversos , Interações Medicamentosas , Quimioterapia Combinada/efeitos adversosRESUMO
El ergotismo es una complicación de la intoxicación aguda y/o el abuso crónico de los derivados del ergot. Se manifiesta por síndrome vasomotor con enfermedad vascular periférica que frecuentemente compromete extremidades. Presentamos cuatro casos de pacientes infectados con el virus de la inmunodeficiencia humana 1 (HIV-1), en tratamiento con antirretrovirales que incluyen inhibidores de la proteasa reforzados con ritonavir, y que habían recibido ergotamina como automedicación. Ellos desarrollaron síntomas de enfermedad vascular periférica y al examen físico sus pulsos estaban disminuidos o ausentes. El Doppler arterial confirmó signos de espasmo arterial difuso en dos de ellos. Se hizo diagnóstico de ergotismo secundario a la asociación de ergotamina-inhibidores de la proteasa. Los pacientes fueron tratados con la discontinuación de las drogas involucradas (inhibidores de la proteasa y ergotamina), bloqueantes cálcicos, profilaxis antitrombótica con enoxaparina, antiagregación con ácido acetil salicílico y uno ellos recibió pentoxifilina e infusión de prostaglandinas vasodilatadoras con mejoría de los síntomas. Discutimos la presentación clínica de esta interacción medicamentosa, difícil de diagnosticar correctamente sin una fuerte sospecha de su existencia.(AU)
Ergotism is a complication of acute intoxication and/or chronic abuse of ergot derivatives. It expresses itself through a vasomotor syndrome with peripheral vascular disease which frequently involves extremities. We report four cases of HIV-1 infected patients treated with antiretroviral drugs including boosted-protease inhibitors who had self-treated themselves with ergotamine. They developed peripheral vascular disease symptoms and their pulses where diminished or absent in the physical examination. Arterial Doppler confirmed diffused arterial spasm in two of them. Ergotism following ergotamine-protease inhibitors association was diagnosed. Patients were treated through the discontinuity of involved drugs (protease inhibitors and ergotamine), calcium blockers; antithrombotic prophylaxis with enoxaparine, antiaggregant therapy with acetylsalicylic acid, and one of them received pentoxifylline and vasodilator prostaglandins infusion, with amelioration of the symptoms. We discuss the clinical presentation of this drug interaction, difficult to diagnose properly without a strong suspicion of its existence.(AU)
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Ergotamina/efeitos adversos , Ergotismo/etiologia , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Ritonavir/efeitos adversos , Interações Medicamentosas , Quimioterapia Combinada/efeitos adversosRESUMO
Ergotism is a complication of acute intoxication and/or chronic abuse of ergot derivatives. It expresses itself through a vasomotor syndrome with peripheral vascular disease which frequently involves extremities. We report four cases of HIV-1 infected patients treated with antiretroviral drugs including boosted-protease inhibitors who had self-treated themselves with ergotamine. They developed peripheral vascular disease symptoms and their pulses where diminished or absent in the physical examination. Arterial Doppler confirmed diffused arterial spasm in two of them. Ergotism following ergotamine-protease inhibitors association was diagnosed. Patients were treated through the discontinuity of involved drugs (protease inhibitors and ergotamine), calcium blockers; antithrombotic prophylaxis with enoxaparine, antiaggregant therapy with acetylsalicylic acid, and one of them received pentoxifylline and vasodilator prostaglandins infusion, with amelioration of the symptoms. We discuss the clinical presentation of this drug interaction, difficult to diagnose properly without a strong suspicion of its existence.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Ergotamina/efeitos adversos , Ergotismo/etiologia , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Ritonavir/efeitos adversos , Adulto , Interações Medicamentosas , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Introducción: Los nuevos inhibidores de la proteasa (IPs), telaprevir y boceprevir, con peginterferón y ribavirina, han aumentado la tasa de respuesta en pacientes con el Virus de la Hepatitis C genotipo 1. Ambos son metabolizados y son inhibidores del CYP3A y sustratos, y telaprevir inhibidor, de la glicoproteína P. Nuestro objetivo es analizar las interacciones entre estos IPs y otros medicamentos. Métodos: Se realizó una revisión sistematizada en PubMed y Cochrane y en resúmenes de congresos (últimos 2-5 años). Se realizó otra búsqueda en Medline para revisar artículos de eficacia en fase II y III, en Micromedex y fichas técnicas. Resultados: En PubMed se encontraron dos artículos sobre ensayos en fase I que cumplían los criterios de búsqueda, no así en las bases de datos de la Cochrane. Se seleccionaron catorce resúmenes de congresos, mayoritariamente estudios en fase I. En la búsqueda libre en Pubmed se localizó un ensayo preclínico in vitro/in vivo que analizaba IPs coadministrados con ritonavir. En los ensayos clínicos en fase II y III, no se hizo ninguna mención sobre interacciones. Conclusiones: Actualmente, disponemos de estudios en fase I que establecen la alteración de parámetros farmacocinéticos al combinar los IPs con medicamentos representativos (potentes inductores, potentes inhibidores, fármacos con alta unión a proteínas plasmáticas, etc.), existiendo evidencias contradictorias de estas interacciones. Su incorporación a la terapéutica debe tener en cuenta la posibilidad de interacciones complejas y no del todo conocidas, en cuanto a su mecanismo de acción, que pudieran comprometer su eficacia o incrementar su toxicidad (AU)
Introduction: The new protease inhibitors (PIs), telaprevir and boceprevir, with peginterferon and ribavirin, have increased the response rate in patients with genotype 1 chronic hepatitis C. Both are metabolized by CYP3A and they are CYP3A inhibitors. Furthermore, they are substrates, also telaprevir is an inhibitor, for P-glycoprotein. Our aim is to analyze the interactions between these IPs and other medications. Method: We performed a systematic review in PubMed and Cochrane database and in conference abstracts of the last 2-5 years. Another search was performed in Medline to check efficacy clinical trials in phase II and III, in Micromedex database and in label information. Results: In PubMed we found two Phase I clinical trials; we did not find any article in the Cochrane database. 14 conference abstracts were selected, mainly there are phase I studies. In the free search in PubMed was located an in vitro / in vivo preclinical study which analyzed the co-administration of IPs and ritonavir. In phase II and III clinical trials, there was no mention about interactions. Conclusions: Currently, there are pharmacokinetic Phase I studies about the interaction between PIs and representative drugs (potent inducers, potent inhibitors, high protein binding drugs, etc.), but the evidence of these interactions is contradictory. Its incorporation into the therapeutic have to take into account the possibility of complex interactions and not entirely known, about their mechanism of action, which might compromise its effectiveness or increase its toxicity (AU)
Assuntos
Humanos , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/farmacocinética , Inibidores da Protease de HIV/uso terapêutico , Oligopeptídeos/efeitos adversos , Oligopeptídeos/farmacocinética , Prolina/análogos & derivados , Prolina/efeitos adversos , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Interações Medicamentosas , Oligopeptídeos/uso terapêutico , Prolina/farmacocinética , Prolina/uso terapêutico , Hepatite C Crônica/tratamento farmacológicoRESUMO
El ergotismo es una enfermedad conocida desde la antigüedad, que se caracteriza por isquemia y, en algunos casos, gangrena de las extremidades. Muchas drogas de uso corriente tienen la capacidad de interactuar con los ergotamínicos desarrollando ergotismo como efecto adverso. Un ejemplo de ello es el ritonavir, un inhibidor de la proteasa utilizado en pacientes con el virus de la inmunodeficiencia humana (HIV). Presentamos un caso de ergotismo en un varón de 39 años con infección por HIV en tratamiento con ritonavir que, después de ingerir 1 mg de tartrato de ergotamina, además de presentar manifestaciones clásicas de la enfermedad, desarrolló un infarto esplénico. Por lo tanto, consideramos importante advertir a los pacientes sobre la posible interacción farmacológica entre los ergotamínicos y otras drogas de uso frecuente y, en particular, el ritonavir en pacientes portadores de HIV.
Ergotism is a clinical condition known since old times and whose main characteristics are ischemia and even limb gangrene. Some drugs have the capacity of interacting with small amounts of ergotamine or its derivatives producing ergotism as a side effect. This is the case of ritonavir, a widely used anti-HIV drug. Here we present a case of ergotism that developed in an HIV positive 39 year old male under treatment with ritonavir, after taking 1 mg of ergotamine tartrate. His clinical picture, apart from showing the basic manifestations of the disease, was associated with splenic infarction. For this reason, we consider important to advise patients about the potential pharmacological interaction between ergotamines and others common drugs and, in particular, ritonavir in HIV positive patients.
Assuntos
Adulto , Humanos , Masculino , Ergotamina/efeitos adversos , Ergotismo/etiologia , Inibidores da Protease de HIV/efeitos adversos , Ritonavir/efeitos adversos , Infarto do Baço/induzido quimicamente , Vasoconstritores/efeitos adversos , Interações Medicamentosas , Infecções por HIV/tratamento farmacológico , Tomografia Computadorizada por Raios XRESUMO
El ergotismo es una enfermedad conocida desde la antig³edad, que se caracteriza por isquemia y, en algunos casos, gangrena de las extremidades. Muchas drogas de uso corriente tienen la capacidad de interactuar con los ergotamínicos desarrollando ergotismo como efecto adverso. Un ejemplo de ello es el ritonavir, un inhibidor de la proteasa utilizado en pacientes con el virus de la inmunodeficiencia humana (HIV). Presentamos un caso de ergotismo en un varón de 39 años con infección por HIV en tratamiento con ritonavir que, después de ingerir 1 mg de tartrato de ergotamina, además de presentar manifestaciones clásicas de la enfermedad, desarrolló un infarto esplénico. Por lo tanto, consideramos importante advertir a los pacientes sobre la posible interacción farmacológica entre los ergotamínicos y otras drogas de uso frecuente y, en particular, el ritonavir en pacientes portadores de HIV.(AU)
Ergotism is a clinical condition known since old times and whose main characteristics are ischemia and even limb gangrene. Some drugs have the capacity of interacting with small amounts of ergotamine or its derivatives producing ergotism as a side effect. This is the case of ritonavir, a widely used anti-HIV drug. Here we present a case of ergotism that developed in an HIV positive 39 year old male under treatment with ritonavir, after taking 1 mg of ergotamine tartrate. His clinical picture, apart from showing the basic manifestations of the disease, was associated with splenic infarction. For this reason, we consider important to advise patients about the potential pharmacological interaction between ergotamines and others common drugs and, in particular, ritonavir in HIV positive patients.(AU)
Assuntos
Adulto , Humanos , Masculino , Ergotamina/efeitos adversos , Ergotismo/etiologia , Inibidores da Protease de HIV/efeitos adversos , Ritonavir/efeitos adversos , Infarto do Baço/induzido quimicamente , Vasoconstritores/efeitos adversos , Interações Medicamentosas , Infecções por HIV/tratamento farmacológico , Tomografia Computadorizada por Raios XRESUMO
The use of new antiretroviral drugs in HIV infection is particularly important in patients with intolerance or resistance to other antiretroviral agents. Raltegravir and maraviroc represent new, important resources in salvage regimens. A reduced grade of liver fibro-steatosis after a combination of raltegravir and maraviroc (second-line) has not been studied and the mechanism by which these new drug classes induced a marked reduction of grade of liver diseases is currently unknown. In the present case report, nested in an ongoing multicentre observational study on the use of new antiretroviral inhibitors in heavy treatment-experienced HIV patients, we evaluated the correlation between a "short therapeutic regimen" raltegravir, maraviroc and fosamprenavir and liver diseases. The aim of this report is to describe the use of a three-drug regimen based on two novel-class antiretroviral agents (raltegravir and maraviroc) plus the protease inhibitor fosamprenavir, in an experienced HIV-infected patient with chronic progressive hepatitis C complicated by liver fibrosis; an overwhelming increased serum creatine kinase level occurred during treatment, and is probably related to integrase inhibitor administration. At present no information is available regarding this correlation.
El uso de nuevos medicamentos antiretrovirales para la infección por VIH es particularmente importante en los pacientes con intolerancia o resistencia a otros agentes antiretrovirales. Raltegravir (RTV) y maraviroc (MRV) representan nuevos e importantes recursos en las terapias de salvamento. Un grado reducido de fibroesteatosis hepática después de una combinación de raltegravir y maraviroc (terapia de segunda línea) no ha sido estudiado, y el mecanismo por el cual estas nuevas clases de droga indujeron una marcada reducción de grado de las enfermedades hepáticas se desconoce hasta el momento. Como parte de la realización en curso de un estudio observacional multicentro acerca del uso de nuevos inhibidores antiretrovirales en pacientes de VIH altamente experimentados en el tratamiento, en el presente reporte de caso se evalúa la correlación entre un "régimen terapéutico corto" (raltegravir, maraviroc y fosamprenavir) y las enfermedades del hígado. El objetivo de este reporte es describir el uso de un régimen de tres medicamentos - basado en dos agentes antiretrovirales de nuevo tipo (raltegravir y maraviroc) además del fosamprenavir inhibidor de la proteasa - en un paciente de VIH experimentado. El paciente también sufre de hepatitis C evolutiva, progresiva, crónica, complicada por fibrosis hepática. Durante el tratamiento, se produjo un aumento extraordinario del nivel de creatina quinasa sérica, el cual probablemente esta relacionado con la administración del inhibidor de la integrasa. Actualmente no hay información disponible con respecto a esta correlación.
Assuntos
Adulto , Humanos , Masculino , Carbamatos/efeitos adversos , Cardiomiopatias/tratamento farmacológico , Creatina Quinase/sangue , Cicloexanos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Fígado Gorduroso/induzido quimicamente , Inibidores da Fusão de HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/efeitos adversos , Inibidores da Protease de HIV/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/induzido quimicamente , Organofosfatos/efeitos adversos , Pirrolidinonas/efeitos adversos , Sulfonamidas/efeitos adversos , Triazóis/efeitos adversos , Carbamatos/uso terapêutico , Cicloexanos/uso terapêutico , Substituição de Medicamentos , Quimioterapia Combinada , Fígado Gorduroso/diagnóstico , Inibidores da Fusão de HIV/uso terapêutico , Inibidores de Integrase de HIV/uso terapêutico , Inibidores da Protease de HIV/uso terapêutico , Cirrose Hepática/diagnóstico , Organofosfatos/uso terapêutico , Pirrolidinonas/uso terapêutico , Sulfonamidas/uso terapêutico , Triazóis/uso terapêuticoRESUMO
Ergotism is a complication of the acute intoxication or chronic abuse of ergot derivatives. It may be manifested by a vasomotor syndrome with peripheral vascular disease frequently involving extremities. We report three patients infected with human immunodeficiency virus (HIV), in antiretroviral treatment (ART) that included a protease inhibitor as ritonavir, and had received self-medicated ergotamine. They developed symptoms of peripheral vascular disease and the physical examination showed no arterial pulses in the affected vessels. Arterial Doppler confirmed signs of diffuse arterial spasm in all of them. An arteriography was performed to the second patient and it showed obliteration of the distal sector of the ulnar and radial arteries. Ergotism secondary to ergotamine-ritonavir association was diagnosed. Patients were treated discontinuing the administration of involved drugs, arterial vasodilators and prophylactic anticoagulation, with marked improvement of symptoms.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ergotamina/intoxicação , Ergotismo/etiologia , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Doença Arterial Periférica/induzido quimicamente , Ritonavir/efeitos adversos , Interações Medicamentosas , Quimioterapia Combinada/efeitos adversos , Vasoconstritores/intoxicaçãoRESUMO
The aim of this study was to determine the impact of antiretroviral therapy on the lipid profile of human immunodeficiency virus (HIV) patients before and after the initiation of highly active antiretroviral therapy (HAART). This was a cross-sectional analysis of patients receiving HAART at a reference center in Belo Horizonte, Brazil, on the basis of medical records from 2002 to 2006. Patients were included if they had at least one lipid test or a clinical or laboratory diagnosis of dyslipidemia/lipodystrophy. Among the 692 patients, 620 met the eligibility criteria. The majority were males (66.5 percent), middle age (average 39 years), had a low educational level (60.4 percent), and low income (51.0 percent). HAART duration ranged from 11 days to 4.6 years, with a mean of 28.6 months (SD = ± 470.19 days). The prevalence of dyslipidemia/lipodystrophy nearly tripled (11.3 percent pre- and 32.4 percent post-HAART). Dyslipidemia was associated with older age (P = 0.007), nucleoside reverse transcriptase inhibitor (NRTI) + protease inhibitor (PI) regimens (P = 0.04), NRTI + non-NRTI (NNRTI) regimens (P = 0.026), the use of stavudine (d4T) in any regimen (P = 0.002) or in NRTI-based regimens (P = 0.006), and longer exposure to HAART (P < 0.000). In addition, there was no correlation between dyslipidemia and gender (P = 0.084). Only 2.0 percent of the patients received treatment for dyslipidemia during the trial. These results show a need for continuous monitoring of patients under antiretroviral therapy, particularly those using NRTI-based regimens, especially when combined with d4T and PIs. Secondly, interventions should be developed to correct metabolic changes.
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Dislipidemias/epidemiologia , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Lipodistrofia/epidemiologia , Inibidores da Transcriptase Reversa/efeitos adversos , Estavudina/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Brasil/epidemiologia , Estudos Transversais , Quimioterapia Combinada/efeitos adversos , Dislipidemias/induzido quimicamente , Lipodistrofia/induzido quimicamente , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
OBJECTIVES: To describe laboratory abnormalities among HIV-infected women and their infants with standard and increased lopinavir/ritonavir (LPV/r) dosing during the third trimester of pregnancy. METHODS: We evaluated data on pregnant women from NISDI cohorts (2002-2009) enrolled in Brazil, who received at least 28 days of LPV/r during the third pregnancy trimester and gave birth to singleton infants. RESULTS: 164 women received LPV/r standard dosing [(798/198 or 800/200 mg/day) (Group 1)] and 70 increased dosing [(> 800/200 mg/day) (Group 2)]. Group 1 was more likely to have advanced clinical disease and to use ARVs for treatment, and less likely to have CD4 counts > 500 cells/mm³. Mean plasma viral load was higher in Group 2. There were statistically significant, but not clinically meaningful, differences between groups in mean AST, ALT, cholesterol, and triglycerides. The proportion of women with Grade 3 or 4 adverse events was very low, with no statistically significant differences between groups in severe adverse events related to ALT, AST, total bilirubin, cholesterol, or triglycerides. There were statistically significant, but not clinically meaningful, differences between infant groups in ALT and creatinine. The proportion of infants with Grade 3 or 4 adverse events was very low, and there were no statistically significant differences in severe adverse events related to ALT, AST, BUN, or creatinine. CONCLUSION: The proportions of women and infants with severe laboratory adverse events were very low. Increased LPV/r dosing during the third trimester of pregnancy appears to be safe for HIV-infected women and their infants.
Assuntos
Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Complicações Infecciosas na Gravidez/tratamento farmacológico , Pirimidinonas/efeitos adversos , Ritonavir/efeitos adversos , Fármacos Anti-HIV/administração & dosagem , Estudos de Coortes , Infecções por HIV/sangue , Inibidores da Protease de HIV/administração & dosagem , Terceiro Trimestre da Gravidez , Complicações Infecciosas na Gravidez/sangue , Pirimidinonas/administração & dosagem , Fatores de Risco , Ritonavir/administração & dosagemRESUMO
INTRODUCTION: HIV-infected children and adolescents treated with highly active antiretroviral therapy (HAART) regimens that include a protease inhibitor (PI) can show significant improvements in clinical outcomes, nutritional status and quality of life. The study aimed to report nutritional and metabolic alterations for pediatric patients continuously exposed to HAART and for healthy controls for up to 1 year. METHODS: Clinical, anthropometric, lipid profile and food intake data were collected prospectively over approximately 12-months for each patient. RESULTS: Fifty-one individuals were studied, of these, 16 were healthy. After 12 months follow-up, HIV-positive individuals remained below the healthy control group parameters. No change was observed concerning food intake. Triglyceride serum levels were higher in patients using protease inhibitor at the onset of the study [PI groups: 114 (43 - 336), and 136 (63 - 271) versus control group: 54.5 (20 - 162); p = 0.003], but after twelve months follow-up, only the group using protease inhibitor for up to two months presented higher values [140 (73 - 273) versus 67.5 (33 - 117); p = 0.004]. HDL-cholesterol was lower in HIV-positive individuals [HIV-positive groups: 36 (27 - 58) and 36 (23 - 43); control 49.5 (34 - 69); p = 0.004]. CONCLUSIONS: HIV-infected children and adolescents treated with highly active antiretroviral therapy showed compromised nutritional parameters compared to a paired healthy control group. Individuals using protease inhibitor presented worse triglyceride serum levels compared to their healthy counterparts.
INTRODUÇÃO: Crianças e adolescentes infectadas pelo HIV e tratadas com terapia antirretroviral de alta potência (TAAP), que inclui inibidor de protease (IP) podem apresentar significante melhora clínica no estado nutricional e na qualidade de vida. O objetivo é relatar as alterações nutricionais e metabólicas em pacientes pediátricos expostos a TAAP e controles saudáveis durante 1 ano. MÉTODOS: O perfil clínico, antropométrico e lipídico, bem como dados da ingestão alimentar foram coletados prospectivamente durante aproximadamente 12 meses. RESULTADOS: Cinquenta e um indivíduos foram estudados. Dezesseis eram saudáveis. Após 12 meses de acompanhamento, indivíduos HIV-positivo permaneceram abaixo dos parâmetros do grupo controle saudável. Nenhuma mudança foi observada em relação à ingestão alimentar. Níveis séricos de triglicerídeos foram maiores em pacientes usando inibidor de protease no começo do estudo [IP grupo: 114 (43 - 336), e 136 (63 - 271) versus grupo controle: 54.5 (20 - 162); p = 0.003], porém após doze meses de acompanhamento, apenas o grupo que recebeu inibidor de protease por não mais do que dois meses apresentou maiores valores [140 (73 - 273) versus 67.5 (33 - 117); p = 0.004]. HDL-colesterol foi menor nos indivíduos HIV-positivos [grupo HIV-positivo: 36 (27 - 58) e 36 (23 - 43); controle 49.5 (34 - 69); p=0.004]. CONCLUSÕES: Crianças e adolescentes infectadas pelo HIV e tratadas com terapia antirretroviral de alta potência tiveram seus parâmetros nutricionais comprometidos quando comparados com o pareado grupo controle. Indivíduos usando inibidor de protease apresentaram piores níveis séricos de triglicerídeos quando comparados com os saudáveis.
Assuntos
Adolescente , Criança , Feminino , Humanos , Masculino , Terapia Antirretroviral de Alta Atividade/efeitos adversos , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Infecções por HIV/tratamento farmacológico , Avaliação Nutricional , Triglicerídeos/sangue , Pesos e Medidas Corporais , Estudos de Casos e Controles , Impedância Elétrica , Seguimentos , Infecções por HIV/sangue , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/uso terapêutico , Estudos LongitudinaisRESUMO
OBJECTIVE: To describe nutritional status, body composition and lipid profile in children and adolescents receiving protease inhibitors. METHODS: Fifty-nine patients, 23 treated with protease inhibitors (group 1) and 36 not using protease inhibitors (group 2). Their dietary intake, anthropometry, bioimpedance analysis and lipid profile variables were measured. RESULTS: There was no difference in nutritional status or body composition between groups at the beginning of the study. After 6 months of follow-up, there was an increase in weight and height in both groups, as well as in waist circumference and subscapular skinfold thickness. In group 2, body mass index and triceps skinfold thickness adequacy were significantly higher after 6 months of follow-up. The groups had similar energy and macronutrient intake at any time point. After 6 months, group 1 had a higher cholesterol intake and group 2 had a higher fiber intake. Triglyceride serum levels were significantly different between the groups, with higher values in G1, at any time point [G1: 153 mg/dl (30-344); 138 (58-378) versus G2: 76 mg/dl (29-378); 76 (29-378)]. After 6 months of follow-up, G1 had higher LDL-cholesterol than G2 [104 mg/dl (40-142) versus 82 (42-145)]. CONCLUSION: The use of protease inhibitors, per se, does not seem to significantly interfere with anthropometric measures, body composition and food intake of HIV-infected children and adolescents. However, this antiretroviral therapy was associated with a significant increase in triglyceride and LDL-cholesterol in our subjects.
Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Lipídeos/sangue , Estado Nutricional/efeitos dos fármacos , Antropometria , Composição Corporal/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Seguimentos , Infecções por HIV/sangue , Fatores de Risco , Estatísticas não Paramétricas , Fatores de TempoRESUMO
Hay múltiples evidencias de que los pacientes infectados por el virus de la inmunodeficiencia humana (VIH), tanto varones como mujeres y tanto adultos como niños, tienen un mayor riesgo de desarrollar enfermedad cardiovascular arteriosclerótica. Dichas evidencias provienen tanto de estudios cuyas variables primarias han sido las propias manifestaciones clínicas de enfermedad cardiovascular arteriosclerótica (infarto agudo de miocardio, isquemia miocárdica silente, accidente vasculocerebral [AVC] y arteriopatía periférica), como diversos marcadores de aterosclerosis prematura y disfunción endotelial determinados a distintos niveles (carótidas, coronarias o arterias periféricas) y con diferentes procedimientos diagnósticos (EIM, CAC, FMD, rigidez arterial, índice tobillo/brazo, etc.). Este exceso de riesgo de enfermedad cardiovascular arteriosclerótica de los pacientes VIH-positivos está manifiestamente asociado con la propia infección por el VIH y con los factores de riesgo cardiovascular clásicos y, de forma menos relevante y homogénea, con el uso de inhibidores de la proteasa de primera generación. La hipertensión arterial, cuya relación con la infección por el VIH es mucho menos clara, se asocia, además de con los factores de riesgo cardiovascular tradicionales, con la existencia de lipodistrofia
A large body of evidence indicates that HIV-infected patients, both men and women, as well as adults and children, have a higher risk of developing arteriosclerotic cardiovascular disease. This evidence comes from studies whose main primary variables were the clinical manifestations of arteriosclerotic cardiovascular disease (acute myocardial infarction, silent myocardial ischemia, stroke and peripheral arterial disease) and the distinct markers of premature atherosclerosis and endothelial dysfunction determined in different sites (carotid, coronary or peripheral arteries) and with distinct diagnostic procedures (carotid intimamedia thickening, coronary artery calcification, flow-mediated vasodilation, arterial rigidity, ankle/arm index, etc.). This excess risk of arteriosclerotic cardiovascular disease in HIV-positive patients is clearly associated with the HIV infection per se and with classical cardiovascular risk factors, and, to a lesser extent and less uniformly, with the use of first-generation protease inhibitors. Hypertension, whose association with HIV infection is far less clear, is related to both traditional cardiovascular risk factors and to lipodystrophy