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J Microbiol Immunol Infect ; 50(6): 789-797, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26857335

RESUMO

BACKGROUND/PURPOSE: Treatment response to switch regimens containing unboosted atazanavir and tenofovir disoproxil fumarate (TDF)/lamivudine guided by therapeutic drug monitoring in human immunodeficiency virus-infected patients is rarely investigated. METHODS: Consecutive patients with plasma human immunodeficiency virus RNA load < 200 copies/mL switching to unboosted atazanavir plus zidovudine-lamivudine (coformulated), abacavir-lamivudine (coformulated), or TDF/lamivudine > 3 months were included for determinations of treatment response, plasma atazanavir concentrations, and single-nucleotide polymorphisms of MDR1, PXR, and UGT1A1 genes from 2010 to 2014. Treatment failure was defined as either discontinuation of atazanavir for any reason or plasma viral load ≥ 200 copies/mL within 96 weeks. RESULTS: During the study period, 128 patients switched to unboosted atazanavir with TDF/lamivudine (TDF group) and 186 patients switched to unboosted atazanavir with two other nucleoside reverse-transcriptase inhibitors (non-TDF group). There were no statistically significant differences in the distributions of single-nucleotide polymorphisms of MDR1 (2677 and 3435), PXR genotypes (63396), and UGT1A1*28 between the two groups. Recommended plasma atazanavir concentrations were achieved in 83.5% and 64.9% of the TDF group and non-TDF group, respectively (p < 0.01). After a median follow-up duration of 96.0 weeks, treatment failure occurred in 19 (14.9%) and 34 (18.3%) patients in the TDF group and non-TDF group, respectively (p = 0.60). Low-level viremia (40-200 copies/mL) before switch (adjusted hazard ratio, 2.12; 95% confidence interval, 1.12-4.01) and without therapeutic drug monitoring (adjusted hazard ratio, 2.08; 95% confidence interval, 1.16-3.73) were risk factors for treatment failure. CONCLUSION: Switch to unboosted atazanavir with TDF/lamivudine achieves a similar treatment response to that with two other nucleoside reverse-transcriptase inhibitors in patients achieving virological suppression with the guidance of therapeutic drug monitoring.


Assuntos
Sulfato de Atazanavir/uso terapêutico , Monitoramento de Medicamentos , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Lamivudina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Tenofovir/uso terapêutico , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Sulfato de Atazanavir/sangue , Combinação de Medicamentos , Feminino , Glucuronosiltransferase/genética , Humanos , Hiperbilirrubinemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Receptor 1 de Sinal de Orientação para Peroxissomos/genética , Testes Farmacogenômicos , Polimorfismo de Nucleotídeo Único/genética , Estudos Retrospectivos , Falha de Tratamento , Carga Viral/efeitos dos fármacos , Adulto Jovem
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