Assuntos
Infecções Fúngicas do Sistema Nervoso Central/diagnóstico , Infecções Fúngicas do Sistema Nervoso Central/etiologia , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/etiologia , Leucemia Linfocítica Crônica de Células B/complicações , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Adenina/análogos & derivados , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Hemocultura/métodos , Infecções Fúngicas do Sistema Nervoso Central/tratamento farmacológico , Humanos , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/patologia , Recidiva Local de Neoplasia , Piperidinas , Pirazóis/administração & dosagem , Pirazóis/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
PURPOSE: Switch to unboosted atazanavir (ATV) is an attractive option due to convenience and tolerability in HIV-positive patients. With limited available data we investigated the determinants of long-term efficacy and the consequences of virological failure of unboosted atazanavir-based regimens. METHODS: Retrospective analysis in two Italian large outpatient clinics including demographic, immunovirological, resistance and pharmacokinetic data. RESULTS: 249 patients receiving atazanavir (400 mg once-daily) plus 2 NRTIs were included; 163 were males (65.5%) and median age was 47 years (42-51.5). Median CD4+ T-cell count was 396/uL (261-583); 146 (58.6%) presented a viral load < 50 copies/mL. Over a median follow up of 157 weeks (106-203) 193 patients (77.5%) were still on treatment with 10 (4%) and 2 (0.8%) stopping for virological failure or toxicity, respectively. Ten patients with virological failure presented newly selected resistance associated mutations (RAMs) for NRTIs (2/10) or ATV (4/10, one I50L). Total cholesterol and triglycerides showed significant decreases at 48 [-4 mg/dL and -41 mg/dL] and 96 weeks [-14 mg/dL and -54 mg/dL] as compared to baseline. At multivariate analysis a genotypic sensitivity score ≤ 1, atazanavir RAMs > 1 and suboptimal adherence were independently associated with virological failure; in lamivudine/emtricitabine-treated patients the presence of M184V (without other NRTI RAMs) was not associated with virological failure. CONCLUSION: Unboosted-atazanavir containing regimens were efficacious (with uncommon virological failures) and well-tolerated (with improvements in lipid profile over time) treatments in HIV-positive patients. Isolated M184V in lamivudine/emtricitabine recipients was not associated with higher failure rates supporting the use of functional ATV-based dual therapies as maintenance strategies.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Oligopeptídeos/uso terapêutico , Piridinas/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Fármacos Anti-HIV/farmacocinética , Terapia Antirretroviral de Alta Atividade , Sulfato de Atazanavir , Contagem de Linfócito CD4 , Farmacorresistência Viral/genética , Substituição de Medicamentos , Feminino , Infecções por HIV/virologia , Inibidores da Protease de HIV/farmacocinética , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/farmacocinética , Piridinas/farmacocinética , RNA Viral/genética , Estudos Retrospectivos , Carga ViralRESUMO
The exposure to DNA reactive carcinogens is known to elicit a specific humoral immunological response, with the production of antibodies towards the carcinogen adducts. In analogy to chemical carcinogens, any chemotherapic, like Adriamycin, undergoes the same adduct formation, and for this reason could elicit specific antibodies. In this case we can suppose that an eventual immunological response could influence the efficacy of chemotherapy. The aim of this study was to verify if adriamycin adducted to DNA or transport proteins can elicit an immunological response of specific anti-adriamycin (ADM) antibodies in sera of 43 cancer patients treated with the drug. No specific antibodies were detected in these individuals. The lack of anti-adriamycin antibodies suggests that the therapeutic exposure to the drug does not elicit a specific immunological response.
Assuntos
Antineoplásicos/imunologia , Adutos de DNA/imunologia , Doxorrubicina/imunologia , Epirubicina/imunologia , Imunoglobulina G/sangue , Neoplasias/sangue , Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Epirubicina/uso terapêutico , Feminino , Humanos , Masculino , Neoplasias/tratamento farmacológicoRESUMO
Between March 1990 and March 1992, 89 patients with recurrent and/or metastatic squamous cell cancer of the head and neck were randomised to receive either intravenous methotrexate (MTX) at a weekly dose of 40 mg/m2 plus lonidamine (LND) given orally at a starting dose of 75 mg three times daily for 3 days and then at a dose of 150 mg three times daily (arm MTX + LND) or methotrexate alone (arm MTX) at the same doses as arm MTX + LND. Complete remissions were observed in 10.5% of the patients in arm MTX + LND, and partial remissions in another 15.8%, yielding a 26.3% response rate. In arm MTX, only partial remissions were observed, yielding an overall response rate of 18.2%. Haematological toxicity was mild in both groups. Mild testicular pain (21%) and myalgias (31%) occurred only in patients treated with LND.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Neoplasias de Cabeça e Pescoço/secundário , Humanos , Indazóis/administração & dosagem , Indazóis/efeitos adversos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de NeoplasiaRESUMO
The authors report on a group of 44 patients operated on for vascular disease, treated with antiplatelet therapy (picotamide). These patients were followed up for a period of 12 months with clinical and instrumental controls (Doppler ultrasound) in order to evaluate the evolution of atherosclerotic disease.