RESUMO
OBJECTIVES: Low plasma concentrations of rifampicin, an essential antituberculosis drug, have been reported particularly among HIV co-infected persons. In a prospective, longitudinal study we measured rifampicin systemic exposure at different timepoints during highly active antiretroviral therapy (HAART). PATIENTS AND METHODS: From May 2006 to April 2007, 16 tuberculosis (TB)/HIV co-infected patients were enrolled in Ouagadougou, Burkina Faso. All patients received fixed dose combinations of rifampicin, isoniazid, pyrazinamide and ethambutol under direct observation and HAART, consisting of a fixed dose combination of stavudine, lamivudine and nevirapine. Rifampicin concentrations during the dosing interval were determined by HPLC at three different timepoints: (i) after 2 weeks of TB therapy and before starting HIV therapy (T0); (ii) after 4 weeks of combined therapy (T1); and (iii) after 10 weeks of combined therapy (T2). RESULTS: The median values of the area under the curve (AUC(0-24)) of rifampicin increased by 39% at T1 (15.69 µgâ·âh/mL; P = 0.01) and by 83% at T2 (20.65 µgâ·âh/mL; P = 0.001) compared with T0 (11.28 µgâ·âh/mL). Similar variations were observed for the median C(max) at T0 (2.24 µg/mL) compared with T2 (2.83 µg/mL; P = 0.003). However, none of the subjects had C(max) levels >8 µg/mL at either T0 or T2. CONCLUSIONS: Rifampicin systemic exposure increased during combined TB and HIV therapy, possibly due to increased drug absorption or decreased oral clearance, but remained invariably low in this population. Studies to define the C(max) rifampicin concentrations, which are associated with a significantly increased risk of treatment failure, are urgently warranted.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Antituberculosos/farmacocinética , Infecções por HIV/tratamento farmacológico , Rifampina/farmacocinética , Tuberculose/tratamento farmacológico , Adulto , Antituberculosos/administração & dosagem , Burkina Faso , Cromatografia Líquida de Alta Pressão , Etambutol/administração & dosagem , Feminino , Infecções por HIV/complicações , Humanos , Isoniazida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Plasma/química , Pirazinamida/administração & dosagem , Rifampina/administração & dosagem , Tuberculose/complicaçõesRESUMO
Because data from countries in Africa are limited, we measured the proportion of extensively drug-resistant (XDR) tuberculosis (TB) cases among TB patients in Burkina Faso for whom retreatment was failing. Of 34 patients with multidrug-resistant TB, 2 had an XDR TB strain. Second-line TB drugs should be strictly controlled to prevent further XDR TB increase.
Assuntos
Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Pulmonar/epidemiologia , Adulto , Antituberculosos/uso terapêutico , Burkina Faso/epidemiologia , Farmacorresistência Bacteriana Múltipla , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Evolução Fatal , Humanos , Masculino , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Falha de Tratamento , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologiaRESUMO
BACKGROUND: Nevirapine (NVP) plasma levels are reduced in patients receiving rifampicin (RFM) for tuberculosis (TB) treatment. We determined variations over time of the pharmacokinetic parameters of NVP in patients who receive RFM. METHODS: HIV-1-infected patients with CD4+ T-lymphocyte count Assuntos
Fármacos Anti-HIV/sangue
, Antibióticos Antituberculose/administração & dosagem
, Infecções por HIV/tratamento farmacológico
, HIV-1
, Nevirapina/sangue
, Rifampina/administração & dosagem
, Tuberculose/tratamento farmacológico
, Adulto
, Fármacos Anti-HIV/farmacocinética
, Fármacos Anti-HIV/uso terapêutico
, Contagem de Linfócito CD4
, Feminino
, Seguimentos
, Infecções por HIV/sangue
, Infecções por HIV/complicações
, Humanos
, Lamivudina/sangue
, Lamivudina/farmacocinética
, Lamivudina/uso terapêutico
, Estudos Longitudinais
, Masculino
, Pessoa de Meia-Idade
, Nevirapina/farmacocinética
, Nevirapina/uso terapêutico
, Estudos Prospectivos
, Estavudina/sangue
, Estavudina/farmacocinética
, Estavudina/uso terapêutico
, Tuberculose/complicações