INTRODUCTION
Global efforts to prevent the spread of human immunodeficiency virus (HIV) have reduced the incidence of new infections 1. The importance of wide coverage and effective suppression of HIV viremia is reflected by the 90-90-90 goals established by the Joint United Nations Program on HIV/AIDS. In addition, Korea’s national health insurance fully covers HIV-related medical expenses for those subscribed to the program to ensure that no patient is untreated for economic reasons.
Highly active antiretroviral therapy (HAART) has significantly reduced HIV-related morbidity and mortality 2. Recent guidelines emphasize that antiretroviral therapy (ART) should be initiated immediately after diagnosis to reduce the risk of HIV transmission and improve the rate of virologic suppression3,4. However, the increase in ART use is expected to increase the prevalence of acquired drug resistance among patients infected with HIV undergoing treatment and transmitted drug resistance (TDR) in newly infected patients 5. Moreover, these drug-resistant mutations (DRM) can be transferred to treatment-naïve patients, thereby negatively affecting the success of primary care and individual prognosis 6.
Current treatment guidelines for using antiretroviral agents against HIV-1 suggest that therapy for a treatment-naïve patient comprises two nucleoside reverse transcriptase inhibitors (NRTIs) in combination with a third active drug from one of three drug classes: integrase strand transfer inhibitor (INSTI), nonnucleoside reverse transcriptase inhibitor (NNRTI), or protease inhibitor (PI) 3,4. The introduction of INSTIs is expected to change TDR demographics in treatment-naïve patients. Furthermore, the emergence of INSTI resistance mutations has been reported 7, including a major INSTI resistance mutation, E92Q, in treatment-naive patients in South Korea8. These results suggest the need for routine monitoring of TDR, including INSTI resistance mutations.
Since 2011, new antiretroviral drugs, such as etravirine (NNRTI) and darunavir (PI), have been frequently prescribed in South Korea. HIV drug resistance testing has been performed to assist in selecting active drugs when altering ART regimens, especially in patients with virologic failure. The clinical guidelines for HIV/AIDS in HIV-infected Koreans9 after 2018 recommend routine HIV drug resistance testing of patients undergoing their first HAART or those considering a change in medication due to virologic failure. The prevalence of HIV TDR in South Korea was 2.5–12.0% between 1999 and 2019, showing an increasing tendency over time 10-13.
In South Korea, the most common subtype of HIV-1 is subtype B. In fact, a nationwide study involving sample collection between 1999 and 2012 revealed that 93.1% of the samples were subtype B 14. In South Korea, subtype B primarily comprises Korean clade B (Bk), a distinct clade from subtype B in other countries, likely due to isolation from other geographic locations15. However, a recent study reported an increase in non-B subtypes from 13.4% to 27.4% between 2015 and 2019, with CRF01_AE being the most prevalent non-B subtype 16.
As of December 2021, the cumulative number of patients with HIV infection in Korea, including non-ethnic Koreans, was 20,715. Approximately 1,000 new HIV cases have been reported annually since 2013, with 90% of the patients being Korean and 10% non-ethnic Koreans17. The centralized laboratory conducted more than 600 genotypic antiretroviral resistance test (GART) annually from hospitals across the country since 2017; hence, more than half of patients with HIV in Korea have undergone HIV-drug resistance (DR) testing at the study institution. Therefore, the analysis conducted by this institution might represent the current HIV-1 drug resistance status and subtype statistics throughout South Korea. Accordingly, this study assesses the trends in HIV-DR and HIV-1 subtypes based on this large sample population.