Asunto(s)
Infecciones Fúngicas del Sistema Nervioso Central/diagnóstico , Infecciones Fúngicas del Sistema Nervioso Central/etiología , Aspergilosis Pulmonar Invasiva/diagnóstico , Aspergilosis Pulmonar Invasiva/etiología , Leucemia Linfocítica Crónica de Células B/complicaciones , Pirazoles/efectos adversos , Pirimidinas/efectos adversos , Adenina/análogos & derivados , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Cultivo de Sangre/métodos , Infecciones Fúngicas del Sistema Nervioso Central/tratamiento farmacológico , Humanos , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/patología , Recurrencia Local de Neoplasia , Piperidinas , Pirazoles/administración & dosificación , Pirazoles/uso terapéutico , Pirimidinas/administración & dosificación , Pirimidinas/uso terapéutico , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: Although the mechanism of atazanavir (ATV)-related hyperbilirubinemia is well identified, its prevalence, risk factors, and association with transaminase flares have rarely been assessed in a large population from the "real life" setting. METHODS: Prospectively collected data on 2,404 patients from the Italian MASTER Cohort and the Italian ATV expanded access program database were examined. Uni- and multivariable Cox proportional hazards regression models were conducted to identify risk factors for grade >or= III hyperbilirubinemia during the administration of ATV. The risk of increased levels of serum alanine aminotransferase (ALT) was compared between patients with or without grade >or= III hyperbilirubinemia in a Cox regression analysis stratified by hepatitis C virus (HCV) serostatus. RESULTS: Grade III and IV hyperbilirubinemia were observed in 1,072 (44.6%) and 174 (7.2%) of the patients, respectively. Higher CD4+ T-cell counts, abnormal bilirubinemia at baseline, and ritonavir co-administration were associated with a higher risk of developing grade >or= III hyperbilirubinemia. In contrast, female gender, clinical class C, and non-nucleoside reverse transcriptase co-administration appeared to be protective. Higher bilirubinemia at baseline and the use of ritonavir were associated with a higher risk of grade IV hyperbilirubinemia. The occurrence of grade >or= III hyperbilirubinemia was not associated with severe hepatotoxicity (hazard ratio 1.00, 95% confidence interval 0.64-1.57; p = 0.997). CONCLUSIONS: Hyperbilirubinemia is a common side effect of an ATV pharmacotherapeutic regimen. However, grade IV increase in bilirubin was rarely found. In most cases, ATV hyperbilirubinemia appeared to be an innocent phenomenon as far as the risk of a subsequent increase in liver enzyme level is concerned.
Asunto(s)
Alanina Transaminasa/sangre , Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Hiperbilirrubinemia/inducido químicamente , Hígado/efectos de los fármacos , Oligopéptidos/efectos adversos , Piridinas/efectos adversos , Adulto , Alanina Transaminasa/metabolismo , Análisis de Varianza , Terapia Antirretroviral Altamente Activa , Sulfato de Atazanavir , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/patología , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Humanos , Hiperbilirrubinemia/epidemiología , Hiperbilirrubinemia/patología , Hígado/enzimología , Masculino , Análisis Multivariante , Prevalencia , Modelos de Riesgos Proporcionales , Factores de Riesgo , Ritonavir/uso terapéutico , Índice de Severidad de la EnfermedadRESUMEN
The degree of infection of memory and naive CD4(+) T cells in patients treated with HAART and with durable undetectable or detectable viral load in plasma was evaluated. The following two groups of patients were analyzed cross-sectionally: (i) patients with undetectable HIV RNA plasma levels during follow-up (responders); (ii) patients with no reduction or with rebound in HIV RNA levels during treatment (non-responders). Patients were examined following 6, 12, 18 and 24 months of HAART, respectively, by quantifying: (i) plasma HIV RNA load; (ii) CD4(+) T cells; (iii) memory and naive CD4(+) T cells; (iv) HIV DNA levels in memory and naive CD4(+) T cells. HIV RNA plasma levels were significantly higher in non-responders vs responders at each time point (P<0.02), while CD4(+) T cell counts as well as memory and naive CD4(+) T cell levels were comparable in both viremic and non-viremic patients. However, higher HIV DNA values were observed in both memory and naive CD4(+) T cells of non-responders vs responders after 18 and 24 months of HAART (P<0.02), suggesting an increased amount of HIV-infected naive CD4(+) T cells and a sustained high degree of infection of memory CD4(+) T cells. Immunological reconstitution following HAART might potentially be hampered in viremic patients despite the absolute increase in CD4(+) T cell counts.