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1.
Antivir Ther ; 17(5): 933-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22297568

RESUMO

We describe the antiviral effect of maraviroc in a patient who had been shedding high levels of HIV-1 in seminal fluid for three years despite an undetectable blood plasma viral load. Adding maraviroc to HAART stopped the seminal shedding. We discuss the mechanisms involved and the effect on sexual transmission.


Assuntos
Cicloexanos/uso terapêutico , Inibidores da Fusão de HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Sêmen/virologia , Triazóis/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/virologia , Humanos , Masculino , Maraviroc , Contagem de Espermatozoides , Carga Viral
2.
Antimicrob Agents Chemother ; 56(3): 1655-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22203586

RESUMO

Efavirenz concentrations were measured in 21 patients during an interruption cycle of the ANRS 106 Window trial. The median efavirenz concentrations in the patients 12 h, 3 days, and 7 days after discontinuation of the drug were 1,962 ng/ml, 416 ng/ml, and 112 ng/ml, respectively. The half-life ranged from 27 to 136 h. No relationship between efavirenz exposure and detection of nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations was demonstrated. Patients who were treated by a lamivudine- or emtricitabine-based regimen had a lower risk of NNRTI mutation selection.


Assuntos
Benzoxazinas/farmacocinética , Desoxicitidina/análogos & derivados , Infecções por HIV/tratamento farmacológico , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/genética , Lamivudina/administração & dosagem , Inibidores da Transcriptase Reversa/farmacocinética , Adulto , Alcinos , Substituição de Aminoácidos , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/farmacocinética , Benzoxazinas/sangue , Cromatografia Líquida de Alta Pressão , Ciclopropanos , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Farmacorresistência Viral , Emtricitabina , Infecções por HIV/virologia , Transcriptase Reversa do HIV/metabolismo , HIV-1/efeitos dos fármacos , Meia-Vida , Humanos , Lamivudina/uso terapêutico , Masculino , Mutação , Inibidores da Transcriptase Reversa/sangue , Carga Viral/efeitos dos fármacos
3.
PLoS One ; 6(6): e21655, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21738752

RESUMO

UNLABELLED: The impact of minor drug-resistant variants of the type 1 immunodeficiency virus (HIV-1) on the failure of antiretroviral therapy remains unclear. We have evaluated the importance of detecting minor populations of viruses resistant to non-nucleoside reverse-transcriptase inhibitors (NNRTI) during intermittent antiretroviral therapy, a high-risk context for the emergence of drug-resistant HIV-1. We carried out a longitudinal study on plasma samples taken from 21 patients given efavirenz and enrolled in the intermittent arm of the ANRS 106 trial. Allele-specific real-time PCR was used to detect and quantify minor K103N mutants during off-therapy periods. The concordance with ultra-deep pyrosequencing was assessed for 11 patients. The pharmacokinetics of efavirenz was assayed to determine whether its variability could influence the emergence of K103N mutants. Allele-specific real-time PCR detected K103N mutants in 15 of the 19 analyzable patients at the end of an off-therapy period while direct sequencing detected mutants in only 6 patients. The frequency of K103N mutants was <0.1% in 7 patients by allele-specific real-time PCR without further selection, and >0.1% in 8. It was 0.1%-10% in 6 of these 8 patients. The mutated virus populations of 4 of these 6 patients underwent further selection and treatment failed for 2 of them. The K103N mutant frequency was >10% in the remaining 2, treatment failed for one. The copy numbers of K103N variants quantified by allele-specific real-time PCR and ultra-deep pyrosequencing agreed closely (ρ = 0.89 P<0.0001). The half-life of efavirenz was higher (50.5 hours) in the 8 patients in whom K103N emerged (>0.1%) than in the 11 patients in whom it did not (32 hours) (P = 0.04). Thus ultrasensitive methods could prove more useful than direct sequencing for predicting treatment failure in some patients. However the presence of minor NNRTI-resistant viruses need not always result in virological escape. TRIAL REGISTRATION: ClinicalTrials.gov NCT00122551.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , Farmacorresistência Viral/genética , HIV-1/efeitos dos fármacos , HIV-1/genética , Adulto , Alcinos , Ciclopropanos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
4.
Arzneimittelforschung ; 60(10): 636-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21125815

RESUMO

Ribavirin (CAS 66510-90-5) associated to peginterferon (CAS 99210-65-8) is the current standard treatment for chronic hepatitis C. Exposure to ribavirin influences the virological response and anemia. Therefore monitoring plasma concentration of ribavirin is a useful tool for individualizing ribavirin dosing regimens. Ribavirin is a substrate of several nucleoside transporters that play a role in its distribution in erythrocytes. After blood sampling, it is essential to limit this mechanism. The aim of this study was to evaluate the influence of temperature and time on ribavirin plasma concentrations. Two blood samples, collected in EDTA tubes, were taken at the same time from 23 patients. One sample was conserved on ice whereas the second one was kept at room temperature during transport to the laboratory. Upon receipt at the laboratory and at different times post-reception (from 1 to 3 h), 1.5 mL of blood from each sample was centrifuged to obtain plasma that was then stored at -20 degrees C until assay. Samples were maintained in the same conditions as during transport for the 3 h. Plasma ribavirin was analysed using an HPLC-UV system. The results showed that mean loss of ribavirin concentration, for samples kept on ice as well as at room temperature, was less than 3%, 9% and 13% after 1, 2 and 3 h, respectively. These results suggest that blood samples for ribavirin analysis can be sent at room temperature within a period of 2 h between sampling and centrifugation.


Assuntos
Antivirais/sangue , Ribavirina/sangue , Antivirais/uso terapêutico , Coleta de Amostras Sanguíneas , Centrifugação , Cromatografia Líquida de Alta Pressão , Ácido Edético , Feminino , Hepatite C/sangue , Hepatite C/tratamento farmacológico , Humanos , Interferons/farmacologia , Interferons/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ribavirina/uso terapêutico , Espectrofotometria Ultravioleta , Temperatura
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