Antiretroviral resistance mutations among antiretroviral treament-na\00EFve and experienced patients in Korea

Abstract

Background: The use of highly active antiretroviral therapy (HAART) has reduced the mortality and morbidity of HIV/AIDS(Human Immunodeficiency Virus/ Acquired Immune Deficiency Syndrome) patients. However, antiretroviral drug resistance is an increasing concern, and its prevalence and pattern differ within geographic areas. The purpose of this study is to assess the prevalence and characteristics of HIV drug resistant amino acid changes among antiretroviral therapy (ART)-naive and experienced patients in Korea.Methods: We investigated antiretroviral resistance mutations in 50 ART-naive and 34 ART-experienced Korean HIV-1 infected patients who visited an urban hospital from February 2007 to March 2011. All ART-experienced patients had virologic failure at the time of resistance testing. HIV RNA pol sequences were obtained using the ViroSeg HIV genotyping system. Resistance mutations were interpreted using the Stanford HIV Drug Resistance database.Results: Most patients (86.9%) were infected with clade B HIV-1, followed by patients with clade AE (4.7%), AG (4.7%) and C (1.2%). 6(12%) ART-naive and 22(64.7%) ART-experienced patients had HIV strains with resistance mutations. In a previous study conducted in Korea, no protease inhibitor (PI) related mutations were found among ART-naive patients. However, 2 types of PI related mutations (encoding L10I and A71T amino acid changes) were identified in the present study. In our study, the V179D amino acid change was the most frequently found mutant virus in ART-naive patients, which accounted for 10%. Among ART-experienced patients, the M184V amino acid change, which confers resistance to nucleoside reverse transcriptase inhibitor (NRTI), was the most frequently found mutation (26.4%). The frequency of thymidine analog mutations (TAM) was 26.2%. Mutations that were categorized as TAM type I were those that encoded the M41L (11.7%), L210W (2.9%), and T215Y (5.8%) amino acid changes and those characterized as TAM type II included D67N (2.9%) and K70R (2.9%). In addition, we also identified the T215D (2.9%) amino acid change, which was otherwise categorized. Most patients (50%) with virologic failure had intermediate to high-level resistance equal to or greater than 2 antiretroviral drugs among those in the prescribed HAART regimen.Conclusion: The prevalence of drug-resistant HIV-1 in ART-naive patients is higher than identified in previous reports, and many Korean HIV-1 infected patients with virologic failure harbor strains with multiple resistance mutations. Continuous monitoring of antiretroviral resistance is recommended in Korea.