RESUMO
PURPOSE: The TOSCANA study aimed to determine the relationship between CD4 cell counts and liver toxicity in patients undergoing treatment simplification or substitution with nevirapine due to the toxicity or poor tolerability of a previous regimen. METHODS: A retrospective analysis was conducted of patients with prior viral suppression who were switched to nevirapine. RESULTS: Overall, 221 patients were included, representing 1134.83 patient-years. The median baseline CD4 cell count at the switch was 464 cells/microL, with 75.6% showing high CD4 cell counts (> or =250 cells/microL in women or > or =400 cells/microL in men). Hepatotoxicity, defined as liver aminotransferase levels 5 times above the upper limit of normal, was detected in 6.7% of the participants with high CD4 cell counts and 13.0% in those with low counts. The relative risk was 0.51 (95% CI 0.21-1.25), and the incidence rates were 2.63 and 1.26 per 100 patient-years for the low- and high-count subpopulations, respectively. Liver toxicity was mild, reversible upon discontinuation, and more likely to appear after 6 months of nevirapine therapy. CONCLUSIONS: Switching to nevirapine was associated with a low incidence of liver toxicity that was unrelated to high CD4 cell counts in patients on prior antiretroviral therapy undergoing simplification or substitution therapy.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Contagem de Linfócito CD4 , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Infecções por HIV/tratamento farmacológico , HIV-1/imunologia , Nevirapina/administração & dosagem , Adulto , Alanina Transaminase/sangue , Fármacos Anti-HIV/efeitos adversos , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/virologia , Feminino , Infecções por HIV/sangue , Infecções por HIV/imunologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Nevirapina/efeitos adversos , Estudos RetrospectivosAssuntos
Alopecia/induzido quimicamente , Inibidores da Protease de HIV/efeitos adversos , Indinavir/efeitos adversos , Ritonavir/efeitos adversos , Quimioterapia Combinada , Inibidores da Protease de HIV/administração & dosagem , Humanos , Indinavir/administração & dosagem , Ritonavir/administração & dosagemAssuntos
Infecções por HIV/virologia , HIV-1/genética , Proteína gp120 do Envelope de HIV/genética , HIV-1/isolamento & purificação , HIV-1/metabolismo , Humanos , Fragmentos de Peptídeos/genética , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo , Receptores de HIV/genética , Receptores de HIV/metabolismo , Recombinação Genética , Espanha , Células Tumorais CultivadasRESUMO
OBJECTIVES: To assess the virologic noninferiority of an antiretroviral treatment simplification with coformulated zidovudine/lamivudine/abacavir (group 1) vs. coformulated zidovudine/lamivudine plus nevirapine (group 2) in HIV-1-infected patients receiving successful first-line highly active antiretroviral therapy. METHODS: This is a prospective, multicenter, open-label, comparative, randomized, noninferiority study. A delta of 15% for differences in virologic suppression <200 copies/mL between groups was prespecified with a 1-sided 0.025 significance level. RESULTS: A total of 134 patients were included into this study: 68 were allocated to group 1 and 66 to group 2. By intention-to-treat analysis (switch equals failure), the percentage of virologic suppression <200 copies/mL (<50 copies/mL) at week 48 was 71.0% (65.1%) and 73.0% (63.3%) in groups 1 and 2, respectively (estimate for differences [<200 copies/mL]: -2.1, 95% CI: -17.4-13.1, P=0.783). Thirteen and 14 patients in groups 1 and 2, respectively, discontinued therapy due to adverse events. Dyslipidemia improved in both groups, with a higher improvement in low-density lipoprotein cholesterol (P=0.049) in group 1. CONCLUSIONS: Group 1 is not inferior to group 2 regarding virologic suppression <200 copies/mL. Both strategies improve lipid profile.