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1.
J Acquir Immune Defic Syndr ; 52(3): 382-6, 2009 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-19654552

RESUMO

BACKGROUND: Boosted darunavir (DRV/r) plus etravirine (ETR), in DUET trials, and raltegravir, in BENCHMRK trials, showed high rates of virologic response in patients with multidrug-resistant HIV-1 infection, particularly when associated with two more fully active antiretroviral drugs. No data from clinical trials, about this combination, are available. PATIENTS AND METHODS: Thirty-two consecutive heavily pretreated patients with multidrug-resistant HIV-1 infection who started a new salvage regimen with RAL (400 mg twice daily), ETR (200 mg twice daily), and DRV/r (600/100 mg twice daily) were studied. Clinical evaluation and immunologic, virologic, and biochemical parameters were collected at baseline and at Weeks 4, 12, and 24. RESULTS: Median baseline characteristics were age 44 years, 13 years on antiretroviral therapy, nine prior highly active antiretroviral therapy regimens, 261 CD4 cells/mL, and HIV-1 RNA 4.2 log10 copies/mL. Sixteen (50%) and 14 (44%) patients were enfuvirtide- and tipranavir-experienced, respectively. Three-class resistance mutations were present in all patients. Three patients (9%) had isolates with three ETR resistance mutations. All patients were DRV-naïve with a median of one DRV resistance mutation. At Weeks 4, 12, and 24, respectively, 63%, 81%, and 94% of patients achieved HIV1-RNA less than 50 copies/mL. Median CD4 cell count increased 30, 73, and 103 cells/mL at Weeks 4, 12, and 24, respectively. No patient had adverse events leading to discontinuation of the regimen. CONCLUSION: The combination of raltegravir, ETR, and DRV/r was a highly effective and well-tolerated antiretroviral salvage regimen in patients infected with multidrug-resistant HIV-1.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral Múltipla , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adulto , Contagem de Linfócito CD4 , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue
2.
J Acquir Immune Defic Syndr ; 49(1): 26-31, 2008 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-18667930

RESUMO

BACKGROUND: The aim of this study was to analyze the incidence of new cases, survival of HIV-1-infected patients with progressive multifocal leukoencephalopathy (PML), and the characteristics of PML-associated immune reconstitution inflammatory syndrome (IRIS). METHODS: Multicenter observational cohort study of all HIV-1-infected patients newly diagnosed of PML in 7 hospitals in Barcelona (Spain) from 2002 to 2006. The annual incidence of PML was calculated. Survival was estimated using the Kaplan-Meier method. IRIS was defined as new onset or rapid worsening of PML shortly after initiation of highly active antiretroviral therapy together with a decline in HIV-1 viral load and rising of CD4 lymphocytes. RESULTS: Sixty-one new cases of PML were diagnosed. The mean survival time was 15 months [95% confidence interval (CI), 11 to 19]. The Kaplan-Meier estimates of the probability of survival were 47.7% (95% CI, 35 to 59) at 6 months, 38.6% (95% CI, 25 to 51) at 12 months, 35.1% (95% CI, 22 to 48) at 24 months, and 25.1% (95% CI, 10 to 40) at 36 months. IRIS was diagnosed in 14 (23%) cases. Mortality was similar in patients with and without IRIS. CONCLUSIONS: PML continues to be one of the deadliest opportunistic infections in acquired immunodeficiency syndrome patients. The development of PML-associated IRIS has no influence on prognosis.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , HIV-1 , Leucoencefalopatia Multifocal Progressiva/complicações , Adulto , Estudos de Coortes , Feminino , Infecções por HIV/mortalidade , Humanos , Doenças do Sistema Imunitário/complicações , Doenças do Sistema Imunitário/mortalidade , Leucoencefalopatia Multifocal Progressiva/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
3.
HIV Clin Trials ; 9(6): 407-17, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19203906

RESUMO

BACKGROUND: Lipoatrophy is the most stigmatizing side effect of stavudine therapy. We assessed the long-term effects of replacing stavudine with tenofovir in HIV-infected patients with lipoatrophy. METHOD: Prospective switch study. Sixty-two clinically stable patients with antiretroviral therapy (ART) containing stavudine, HIV-1 RNA <50 copies/mL, and lipoatrophy at least in the face on physical examination were included. All patients switched from stavudine to tenofovir without changing any other drug. Objective (malar ultasonography, bioelectrical impedance analysis) and subjective measures of lipoatrophy were assessed. RESULTS: Median age at baseline was 40 years, 44 patients (71%) were male, and median time on stavudine was 4.8 years. Median malar fat thickness increased 0.8 mm (25%) 24 months after switching. Total fat mass increased 3.9 kg (21%). Plasma lactate levels decreased significantly, mainly in patients with baseline hyperlactatemia (from 3.05 to 1.19 mmol/L). Significant improvement in total cholesterol (-12%), triglycerides (-31%), and total cholesterol/HDL cholesterol ratio (-11%) was observed at Month 24. CONCLUSIONS: In this study, switching from stavudine to tenofovir maintained durable virologic suppression when the HAART regimen included a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor, led to a slow improvement of lipoatrophy, and improved the lipid profile and lactate levels with excellent tolerability. These results support the proactive change of stavudine to tenofovir.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/patologia , Lipídeos/sangue , Organofosfonatos/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Estavudina/uso terapêutico , Adenina/administração & dosagem , Adenina/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Composição Corporal/efeitos dos fármacos , Esquema de Medicação , Quimioterapia Combinada , Face , Feminino , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Síndrome de Lipodistrofia Associada ao HIV/induzido quimicamente , Síndrome de Lipodistrofia Associada ao HIV/tratamento farmacológico , Humanos , Lactatos/sangue , Masculino , Pessoa de Meia-Idade , Mitocôndrias/efeitos dos fármacos , Organofosfonatos/administração & dosagem , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Estavudina/administração & dosagem , Estavudina/efeitos adversos , Gordura Subcutânea/diagnóstico por imagem , Gordura Subcutânea/efeitos dos fármacos , Tenofovir , Resultado do Tratamento , Ultrassonografia
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