RESUMEN
BACKGROUND: In South Korea, about 20 types of antiretroviral drugs are used in the treatment of patients with human immunodeficiency virus/acquired immune deficiency syndrome. Since 2010, raltegravir, etravirine, and darunavir have been spotlighted as new drugs for highly active antiretroviral therapy (HAART)-experienced adults with resistant HIV-1 in South Korea. In this study, we investigated potential susceptibility of pseudoviruses derived from treatment-experienced Korean patients to etravirine vs efavirenz and to darunavir vs amprenavir and indinavir using a modified single-round assay. METHODS: Pseudoviruses derived from nine treatment-experienced patients infected with HIV-1 were investigated by comparison with the wild-type strain pNL4-3. The 50% inhibitory concentration (IC50) values were calculated and drug susceptibility was compared. The intensity of genotypic drug resistance was classified based on the 'SIR' interpretation of the Stanford data base. RESULTS: Drug susceptibility was generally higher for etravirine and darunavir compared with efavirenz, amprenavir, and indinavir in pseudoviruses derived from treatment-experienced patients. Pseudoviruses derived from patients KRB4025 and KRB8014, who exhibited long-term use of protease inhibitors, showed an outside of tested drug concentration, especially for amprenavir and indinavir. However, they exhibited a lower fold-change in resistance to darunavir. CONCLUSIONS: Etravirine and darunavir have been used in HAART since 2010 in South Korea. Therefore, these antiretroviral drugs together with other newly introduced antiretroviral drugs are interesting for the optimal treatment of patients with treatment failure. This study may help to find a more effective HAART in the case of HIV-1 infected patients that have difficulty being treated.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/virología , Fármacos Anti-VIH/farmacología , Darunavir/farmacología , Infecciones por VIH/virología , VIH-1/genética , Pruebas de Sensibilidad Microbiana , Piridazinas/farmacología , Recombinación Genética , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Darunavir/uso terapéutico , Farmacorresistencia Viral , Genotipo , Infecciones por VIH/tratamiento farmacológico , Humanos , Concentración 50 Inhibidora , Mutación , Nitrilos , Fenotipo , Precursores de Proteínas/genética , Piridazinas/uso terapéutico , Pirimidinas , República de Corea , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
BACKGROUND: Genotypic drug resistance assay has been the only method available to provide information related to drug resistance in South Korea since 1999. Phenotypic assay is also a useful method to predict a patient's state related to antiretroviral drug resistance. However, commercial systems and methods for phenotyping have not been introduced into South Korea. OBJECTIVES: To establish and apply modified phenotypic drug susceptibility assay using treatment-experienced patients' derived HIV-1 in South Korea. STUDY DESIGN: The genotypic drug resistance and phenotypic drug susceptibility of two different methods, Stanford HIV Drug Resistance Database (Stanford DB) and modified phenotypic drug susceptibility assay were compared especially focused on the HIV-1 protease (PR) and reverse transcriptase (RT) sequences. RESULTS: There was some discordance in comparing drug susceptibility results (a modified drug susceptibility assay) with the predicted genotypic drug resistance (Stanford DB). Phenotypic drug resistance showed the following order for pseudoviruses from treatment-experienced patients infected with HIV/AIDS: Efavirenz (EFV, 21 to 1,319-fold change), Lamivudine (3TC, 31 to >189-fold change), Indinavir sulfate (IDV, 26 to 63-fold change), Amprenavir (APV, 4 to 35-fold change) and Zidovudine (AZT, 20 to 634-fold change). For patient KRC3221, the AZT-related phenotypic drug resistance was the greatest, with 634-fold change compared with the wild type. CONCLUSIONS: Application of this modified phenotypic drug susceptibility assay is expected to help in predicting drug resistance as a guideline for clinicians to obtain a combined interpretation among genotyping, phenotyping and effective clinical treatments.
Asunto(s)
Farmacorresistencia Viral , VIH-1/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Inhibidores de Proteasas/farmacología , Inhibidores de la Transcriptasa Inversa/farmacología , Fármacos Anti-VIH/farmacología , Farmacorresistencia Viral/efectos de los fármacos , Farmacorresistencia Viral/genética , Regulación de la Expresión Génica/efectos de los fármacos , Genotipo , Proteínas Fluorescentes Verdes/genética , Células HEK293 , VIH-1/genética , Humanos , FenotipoRESUMEN
Pulse diagnosis, which is one of methods of diagnosis, is an important factor in oriental medicine. However, a problem in diagnosis with the pulse is that there is no objective standard. Therefore, the practitioners pass on the skill and students learn about pulse diagnosis as a method that depends on speech. In this study, the electronic pulse wave reproduction apparatus, which is an objective and accurate means for measuring the pulse, was developed. The previous model reproduced the pulse wave in one part of the point, but it was made by using three pairs of voice coil motors (VCM) in order to similarly express the three parts of the pulse: Cun, Guan and Chi. To evaluate this system, the output of the pulse wave was confirmed in order to reproduce the pulse wave with these settings. Consequently, the targets for slow pulse and rapid pulse have a 7 ms standard deviation, which is within the error tolerance. A voltage value of H(1), utilized to verify vacuous pulse and the replete pulse, has a standard deviation range of 4.7-5.4 mV. This system, which is similar to a person's pulse diagnosis, can be used to educate others in pulse diagnosis both quantitatively and scientifically.