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      HIV-1 Drug Resistance Mutations and Their Clinical Implications in South Korea

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      https://www.riss.kr/link?id=A108669775

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      다국어 초록 (Multilingual Abstract) kakao i 다국어 번역

      Background: While the incidence of new human immunodeficiency virus (HIV) infections has decreased, the dramatic rise in antiretroviral therapy (ART) use will likely increase the prevalence of drug resistance mutations (DRMs). This study aimed to investigate the prevalence and profile of HIV-1 DRMs in ART-naïve and ART-experienced patients in South Korea and determine the correlation between the degree of DRM and the clinical response.
      Methods: Thirty-six ART-naïve and 8 ART-experienced HIV-1–infected Korean patients referred for standard genotypic resistance testing (SGRT) between 2018 and 2019 were enrolled. Their SGRT results, viral loads, and CD4+ T cell counts were analyzed.
      Results: Protease inhibitor (PI)-related DRMs were the most frequently observed mutations in ART-naïve (52.8%) and ART-experienced (50.0%) groups, followed by nonnucleoside reverse transcriptase inhibitor (NNRTI)-related and integrase inhibitor (INSTI)-related DRMs. Major DRMs were observed only as NNRTI-related DRMs. The prevalence of transmitted drug resistance (TDR) was 55.6%, which was markedly higher than that previously reported. The changes in viral loads and CD4 counts in ART-naïve patients showed no correlation with the degree of DRM (major, minor, and none). All ART-naïve patients were treated with INSTI-based regimens, and most showed very good responses.
      Conclusions: The distribution of HIV-1 DRMs in Korean patients was biased toward PI-related and minor DRMs, and DRM severity was not associated with the clinical response. This study provides valuable information on the recent DRM profile among Korean HIV-1 patients and emphasizes the importance of drug resistance genotyping.
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      Background: While the incidence of new human immunodeficiency virus (HIV) infections has decreased, the dramatic rise in antiretroviral therapy (ART) use will likely increase the prevalence of drug resistance mutations (DRMs). This study aimed to inve...

      Background: While the incidence of new human immunodeficiency virus (HIV) infections has decreased, the dramatic rise in antiretroviral therapy (ART) use will likely increase the prevalence of drug resistance mutations (DRMs). This study aimed to investigate the prevalence and profile of HIV-1 DRMs in ART-naïve and ART-experienced patients in South Korea and determine the correlation between the degree of DRM and the clinical response.
      Methods: Thirty-six ART-naïve and 8 ART-experienced HIV-1–infected Korean patients referred for standard genotypic resistance testing (SGRT) between 2018 and 2019 were enrolled. Their SGRT results, viral loads, and CD4+ T cell counts were analyzed.
      Results: Protease inhibitor (PI)-related DRMs were the most frequently observed mutations in ART-naïve (52.8%) and ART-experienced (50.0%) groups, followed by nonnucleoside reverse transcriptase inhibitor (NNRTI)-related and integrase inhibitor (INSTI)-related DRMs. Major DRMs were observed only as NNRTI-related DRMs. The prevalence of transmitted drug resistance (TDR) was 55.6%, which was markedly higher than that previously reported. The changes in viral loads and CD4 counts in ART-naïve patients showed no correlation with the degree of DRM (major, minor, and none). All ART-naïve patients were treated with INSTI-based regimens, and most showed very good responses.
      Conclusions: The distribution of HIV-1 DRMs in Korean patients was biased toward PI-related and minor DRMs, and DRM severity was not associated with the clinical response. This study provides valuable information on the recent DRM profile among Korean HIV-1 patients and emphasizes the importance of drug resistance genotyping.

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      참고문헌 (Reference)

      1 The Korean Society for AIDS, "The 2018 Clinical Guidelines for the Diagnosis and Treatment of HIV/AIDS in HIV-Infected Koreans" 대한감염학회 51 (51): 77-88, 2019

      2 McColl DJ, "Strand transfer inhibitors of HIV-1 integrase : bringing IN a new era of antiretroviral therapy" 85 : 101-118, 2010

      3 Chin BS, "Short Communication : Increase of HIV-1 K103N transmitted drug resistance and its association with efavirenz use in South Korea" 31 : 603-607, 2015

      4 Lwanga SK, "Sample size determination in health studies: a practical manual"

      5 Bang JI, "Prevalence of primary antiretroviral resistance : trends in Korea" 24 : 83-85, 2008

      6 Anstett K, "Polymorphic substitution E157Q in HIV-1 integrase increases R263K-mediated dolutegravir resistance and decreases DNA binding activity" 71 : 2083-2088, 2016

      7 Bartlett JA, "Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults" 15 : 1369-1377, 2001

      8 CDC NCHHSTP, "New HIV Infections Drop 18 Percent in Six Years"

      9 Choi JY, "National survey for drug-resistant variants in newly diagnosed antiretroviral drug-naive patients with HIV/AIDS in South Korea : 1999-2005" 49 : 237-242, 2008

      10 Meixenberger K, "Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors" 14 : 223-, 2017

      1 The Korean Society for AIDS, "The 2018 Clinical Guidelines for the Diagnosis and Treatment of HIV/AIDS in HIV-Infected Koreans" 대한감염학회 51 (51): 77-88, 2019

      2 McColl DJ, "Strand transfer inhibitors of HIV-1 integrase : bringing IN a new era of antiretroviral therapy" 85 : 101-118, 2010

      3 Chin BS, "Short Communication : Increase of HIV-1 K103N transmitted drug resistance and its association with efavirenz use in South Korea" 31 : 603-607, 2015

      4 Lwanga SK, "Sample size determination in health studies: a practical manual"

      5 Bang JI, "Prevalence of primary antiretroviral resistance : trends in Korea" 24 : 83-85, 2008

      6 Anstett K, "Polymorphic substitution E157Q in HIV-1 integrase increases R263K-mediated dolutegravir resistance and decreases DNA binding activity" 71 : 2083-2088, 2016

      7 Bartlett JA, "Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults" 15 : 1369-1377, 2001

      8 CDC NCHHSTP, "New HIV Infections Drop 18 Percent in Six Years"

      9 Choi JY, "National survey for drug-resistant variants in newly diagnosed antiretroviral drug-naive patients with HIV/AIDS in South Korea : 1999-2005" 49 : 237-242, 2008

      10 Meixenberger K, "Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors" 14 : 223-, 2017

      11 Stanford HIVDB, "Major HIV-1 Drug Resistance Mutations"

      12 Lok JJ, "Long-term increase in CD4+ T-cell counts during combination antiretroviral therapy for HIV-1 infection" 24 : 1867-1876, 2010

      13 Chin BS, "Inverse relationship between viral load and genotypic resistance mutations in Korean patients with primary HIV type 1 infections" 22 : 1142-1147, 2006

      14 김연재 ; 진범식 ; 김가연 ; 신형식, "Integrase Strand Transfer Inhibitor Resistance Mutations in Antiretroviral Treatment-naïve Patients in Korea: a Prospective, Observational Study" 대한의학회 33 (33): 1-5, 2018

      15 Kelley CF, "Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment" 48 : 787-794, 2009

      16 Kim MH, "HIV antiretroviral resistance mutations among antiretroviral treatment-naive and-experienced patients in South Korea" 29 : 1617-1620, 2013

      17 Panel on Antiretroviral Guidelines for Adults and Adolescents, "Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV"

      18 Park SW, "Genotypic resistance of antiretroviral drugs among drug-naive HIV type 1 patients with the background of long-term access-easy zidovudine therapy" 19 : 1039-1043, 2003

      19 Kim JY, "Genetic variation of the HIV-1 integrase region in newly diagnosed anti-retroviral drug-naive patients with HIV/AIDS in Korea" 17 : 1155-1159, 2011

      20 Phillips AN, "Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment : modelling study and economic analysis" 1 : e85-e93, 2014

      21 Li T, "Drug resistance mutation profiles of the drug-naïve and first-line regimen-treated HIV-1-infected population of Suzhou, China" 32 : 271-279, 2017

      22 Hattori J, "Characteristics of transmitted drug-resistant HIV-1 in recently infected treatment-naive patients in Japan" 71 : 367-373, 2016

      23 Onoriode Digban T, "Analyses of HIV-1 integrase gene sequences among treatment-naive patients in the Eastern Cape, South Africa" 92 : 1165-1172, 2020

      24 Wensing AM, "2019 update of the drug resistance mutations in HIV-1" 27 : 111-121, 2019

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