Drug susceptibility of human immunodeficiency virus type 1-derived pseudoviruses from treatment-experienced patients to protease inhibitors and reverse transcriptase inhibitors, using a modified single-round assay

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.