RESUMO
BACKGROUND: This Phase IIb study explored the antiviral activity and safety of the investigational CCR5 antagonist aplaviroc (APL) in antiretroviral-naive patients harbouring R5-tropic virus. METHODS: One hundred and forty-seven patients were randomized 2:2:1 to one of two APL dosing regimens or efavirenz (EFV). All dosage arms were administered twice daily and in combination with lamivudine/zidovudine (3TC/ZDV; Combivir, COM). Efficacy, safety, and pharmacokinetic parameters were assessed. RESULTS: This study was prematurely terminated due to APL-associated idiosyncratic hepatotoxicity. The primary endpoint of the study was the proportion of patients with plasma HIV-1 RNA <400 copies/ml who remained on randomized treatment through week 12. Of the 147 patients enrolled, 145 patients received one dose of treatment and were included in the intention-to-treat population. The proportion of patients with HIV-1 RNA <400 copies/ml at week 12 was 53%, 50% and 66% in the APL 600 mg twice daily, APL 800 mg twice daily, and EFV arms, respectively. Common clinical adverse events (AEs) were diarrhoea, nausea, fatigue and headache. APL demonstrated non-linear pharmacokinetics with high interpatient variability. In addition to the hepatic findings, there was an apparent dose-response relationship in the incidence of diarrhoea. CONCLUSIONS: Whereas target plasma concentrations of APL were achieved, the antiviral activity of APL as the third agent in a triple drug regimen did not appear to be comparable to EFV in this treatment-naive patient population.
Assuntos
Fármacos Anti-HIV , Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Inibidores da Fusão de HIV/administração & dosagem , Inibidores da Fusão de HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Inibidores da Transcriptase Reversa , Compostos de Espiro/administração & dosagem , Compostos de Espiro/efeitos adversos , Adulto , Idoso , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Benzoatos/farmacocinética , Benzoatos/uso terapêutico , Dicetopiperazinas , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Inibidores da Fusão de HIV/farmacocinética , Inibidores da Fusão de HIV/uso terapêutico , Infecções por HIV/virologia , Humanos , Lamivudina/administração & dosagem , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Piperazinas/farmacocinética , Piperazinas/uso terapêutico , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/uso terapêutico , Compostos de Espiro/farmacocinética , Compostos de Espiro/uso terapêutico , Resultado do Tratamento , Zidovudina/administração & dosagem , Zidovudina/uso terapêuticoRESUMO
BACKGROUND: Zidovudine, lamivudine, and efavirenz comprise a highly effective and well-tolerated triple regimen for antiretroviral-naive patients. Evaluating other unique nucleoside reverse-transcriptase inhibitor (NRTI) combinations for long-term viral suppression is desirable. METHODS: This multicenter, randomized, double-blind noninferiority clinical trial compared the efficacy and safety of abacavir with that of zidovudine plus lamivudine and efavirenz in 649 antiretroviral-naive HIV-infected patients. The primary objective was a comparison of proportions of patients achieving plasma HIV-1 RNA levels Assuntos
Didesoxinucleosídeos/uso terapêutico
, Infecções por HIV/tratamento farmacológico
, Lamivudina/uso terapêutico
, Oxazinas/uso terapêutico
, Zidovudina/uso terapêutico
, Adolescente
, Adulto
, Idoso
, Alcinos
, Fármacos Anti-HIV/efeitos adversos
, Fármacos Anti-HIV/uso terapêutico
, Benzoxazinas
, Contagem de Linfócito CD4
, Ciclopropanos
, Didesoxinucleosídeos/efeitos adversos
, Método Duplo-Cego
, Quimioterapia Combinada
, Feminino
, Humanos
, Lamivudina/efeitos adversos
, Masculino
, Pessoa de Meia-Idade
, Oxazinas/efeitos adversos
, RNA Viral/sangue
, Zidovudina/efeitos adversos