RESUMO
OBJECTIVES: Complex antiretroviral regimens can be associated with increased toxicity and poor adherence. Our aim was to compare the efficacy and safety of switching to two simplified, class-sparing antiretroviral regimens. METHODS: We conducted a randomized, open-label study in 236 patients with virologic suppression who were taking a three- or four-drug protease inhibitor or non-nucleoside reverse transcriptase inhibitor regimen for > or = 18 months. Patients received lopinavir/ritonavir (LPV/r) 533 mg/133 mg twice daily + efavirenz (EFV) 600 mg once daily or EFV + two nucleoside reverse transcriptase inhibitors (NRTI). Primary study endpoint was time to first virologic failure (VF, confirmed HIV-1 RNA > 200 copies/ml) or discontinuation because of study drug-related toxicity. RESULTS: After 2.1 years of follow up, patients receiving LPV/r + EFV discontinued treatment at a greater rate than patients receiving EFV + NRTI (P < 0.001). Twenty-one patients developed VF (14 receiving LPV/r + EFV and seven receiving EFV + NRTI) and 26 discontinued because of a study drug-related toxicity (20 receiving LPV/r + EFV and six receiving EFV + NRTI). Time to VF or study drug related-toxicity discontinuation was significantly shorter for LPV/r + EFV than EFV + NRTIs (P = 0.0015). A significantly higher risk of drug-related toxicity occurred with LPV/r + EFV, mainly for increased triglycerides (P = 0021). A trend toward a higher VF rate occurred with LPV/r + EFV in an intent-to-treat and as-treated analyses (P = 0.088 and P = 0.063 respectively). CONCLUSIONS: Switching to EFV + NRTI resulted in better outcomes, fewer drug-related toxicity discontinuations and a trend to fewer virologic failures compared to switching to LPV/r + EFV.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1 , Adulto , Alcinos , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Benzoxazinas/efeitos adversos , Benzoxazinas/uso terapêutico , Contagem de Linfócito CD4 , Ciclopropanos , Farmacorresistência Viral , Feminino , Seguimentos , Infecções por HIV/imunologia , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Humanos , Lopinavir , Masculino , Pessoa de Meia-Idade , Pirimidinonas/efeitos adversos , Pirimidinonas/uso terapêutico , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/efeitos adversos , Ritonavir/uso terapêutico , Resultado do TratamentoRESUMO
Panacos Pharmaceuticals Inc is developing the HIV Gag protein and viral maturation inhibitor bevirimat for the potential oral treatment of HIV infection. Phase II clinical trials are underway and phase III trials expected to commence in 2007.
Assuntos
Produtos do Gene gag/antagonistas & inibidores , Infecções por HIV/tratamento farmacológico , HIV-1/metabolismo , Succinatos/farmacologia , Triterpenos/farmacologia , Animais , Ensaios Clínicos Fase II como Assunto , Avaliação Pré-Clínica de Medicamentos , Infecções por HIV/metabolismo , Humanos , Succinatos/efeitos adversos , Succinatos/farmacocinética , Succinatos/uso terapêutico , Triterpenos/efeitos adversos , Triterpenos/farmacocinética , Triterpenos/uso terapêuticoRESUMO
Cytomegalovirus (CMV) disease is a common complication of patients with advanced human immunodeficiency virus infection. The aim of the present study, based on a case-cohort design, was to determine the predictive value of follow-up and baseline qualitative plasma CMV polymerase chain reaction (PCR) values for CMV end-organ disease in 378 patients (158 who progressed to CMV end-organ disease and 220 who did not develop CMV disease). These patients are part of the full AIDS Clinical Trials Group 204 multinational study (1227 patients), a randomized, controlled trial that compared the effects of valacyclovir with those of acyclovir for CMV disease prevention. Baseline PCR positivity was a significant risk factor for CMV disease progression (relative risk [RR], 1.81; 95% confidence interval [CI], 1.09-3.00). In multivariate analyses, time-updated PCR positivity was strongly associated with progression to CMV end-organ disease (RR, 4.42; 95% CI, 2.87-6.81). Change in cumulative PCR status was informative for the risk of subsequent CMV disease.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Aciclovir/análogos & derivados , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/genética , Infecções por HIV/virologia , Valina/análogos & derivados , Infecções Oportunistas Relacionadas com a AIDS/virologia , Aciclovir/uso terapêutico , Adulto , Estudos de Casos e Controles , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/virologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Análise Multivariada , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Fatores de Risco , Valaciclovir , Valina/uso terapêuticoRESUMO
To compare long-term virologic benefits of antiretroviral regimens in persons with advanced human immunodeficiency virus (HIV) disease, a randomized, open-label study was conducted of 517 subjects with no or limited previous experience with antiretroviral therapy. Subjects received lamivudine plus zidovudine and indinavir (indinavir group), efavirenz plus indinavir (efavirenz + indinavir group), or nelfinavir plus indinavir (nelfinavir + indinavir group) and were monitored for 2.1 years. Virologic failure was lower in the efavirenz + indinavir group (P=.04) and higher in the nelfinavir + indinavir group (P=.006), compared with that in the indinavir group. No difference in grade 3 or 4 adverse event rates in the efavirenz + indinavir group (P=.97) and a trend toward an increased rate in the nelfinavir + indinavir group (P=.07), compared with the indinavir group, were noted. A 4-drug regimen containing efavirenz plus indinavir resulted in a superior virologic response, whereas one containing nelfinavir plus indinavir resulted in an inferior response and a greater likelihood of toxicity.