RESUMO
OBJECTIVES: To describe the pharmacokinetics of maraviroc when dosed at 150 or 300 mg once daily with 800/100 mg of darunavir/ritonavir. METHODS: A retrospective case-note review of HIV-infected adults taking maraviroc was conducted. Patients on a maraviroc-based regimen for a minimum of 5 weeks were grouped as receiving: (i) 300 mg of maraviroc twice daily with 245 mg of tenofovir/200 mg of emtricitabine; (ii) 300 mg of maraviroc once daily with 800/100 mg of darunavir/ritonavir once daily; and (iii) 150 mg of maraviroc once daily with 800/100 mg of darunavir/ritonavir once daily. C(trough) and C(peak) data were collected at 2, 12 or 24 h post-dose. RESULTS: Sixty-six patients were included, providing 115 samples. The median (IQR) C(peak) was 378 (350-640) ng/mL for 300 mg of maraviroc twice daily with 245 mg of tenofovir/200 mg of emtricitabine (n=9), 728 (378-935) ng/mL for 300 mg of maraviroc once daily with darunavir/ritonavir (n=29) and 364 (104-624) ng/mL for 150 mg of maraviroc once daily with darunavir/ritonavir (n=2; P=0.24). The median (IQR) C(trough) was 46 (33-61) ng/mL for 300 mg of maraviroc twice daily with 245 mg of tenofovir/200 mg of emtricitabine (n=12), 70 (49-97) ng/mL for 300 mg of maraviroc once daily with darunavir/ritonavir (n=34) and 43 (35-55) ng/mL for 150 mg of maraviroc once daily with darunavir/ritonavir (n=17; P=0.001). The maraviroc C(trough) in black patients (n=34) was 61 (45-110) ng/mL and in white patients (n=29) it was 49 (42-70) ng/mL (P=0.04). The C(peak) in black patients (n=20) was 800 (397-1060) ng/mL versus 387 (336-723) ng/mL in white patients (n=20; P=0.02). CONCLUSIONS: Once daily coadministration of 300 mg of maraviroc with 800/100 mg of darunavir/ritonavir was well tolerated and had favourable pharmacokinetics when compared with 300 mg of maraviroc twice daily with 245 mg of tenofovir/200 mg of emtricitabine. A 24% higher C(trough) and 107% higher C(peak) was seen in black patients compared with white patients.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Cicloexanos/administração & dosagem , Cicloexanos/farmacocinética , Infecções por HIV/tratamento farmacológico , Ritonavir/administração & dosagem , Sulfonamidas/administração & dosagem , Triazóis/administração & dosagem , Triazóis/farmacocinética , Adulto , Darunavir , Interações Medicamentosas , Feminino , Humanos , Masculino , Maraviroc , Pessoa de Meia-Idade , Estudos RetrospectivosAssuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Serviços de Saúde Materna , Complicações Infecciosas na Gravidez/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Adulto , Terapia Antirretroviral de Alta Atividade , Parto Obstétrico/métodos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Fórmulas Infantis , Recém-Nascido , Masculino , Profilaxia Pós-Exposição/estatística & dados numéricos , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/imunologia , Prevalência , Sociedades Médicas , Reino Unido/epidemiologiaRESUMO
PENTA Guidelines aim to provide practical recommendations for treating children with HIV infection in Europe. Changes to guidance since 2004 have been informed by new evidence and by expectations of better outcomes following the ongoing success of antiretroviral therapy (ART). Participation in PENTA trials of simplifying treatment is encouraged. The main changes are in the following sections: 'When to start ART': Treatment is recommended for all infants, and at higher CD4 cell counts and percentages in older children, in line with changes to adult guidelines. The number of age bands has been reduced to simplify and harmonize with other paediatric guidelines. Greater emphasis is placed on CD4 cell count in children over 5 years, and guidance is provided where CD4% and CD4 criteria differ. 'What to start with': A three-drug regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) remains the first choice combination. Lamivudine and abacavir are the NRTI backbone of choice for most children, based on long-term follow-up in the PENTA 5 trial. Stavudine is no longer recommended. Whether to start with an NNRTI or PI remains unclear, but PENPACT 1 trial results in 2009 may help to inform this. All PIs should be ritonavir boosted. Recommendations on use of resistance testing, therapeutic drug monitoring and HLA testing draw from data in adults and from European paediatric cohort studies. Recently updated US and WHO paediatric guidelines provide more detailed review of the evidence base. Differences between guidelines are highlighted and explained.