M Sayan1,2, A Gündüz3, G Ersöz4, A İnan5, A Deveci6, G Özgür7, F Sargın8, G Karagöz9, A İnci10, D İnan11, A Ülçay12, I Karaoğlan13, S Kaya14, S S Kutlu15, K Süer16, A Çağatay17, H Akalın18. 1. a Faculty of Medicine, Clinical Laboratory, PCR Unit , University of Kocaeli , Kocaeli , Turkey. 2. b Research Center of Experimental Health Sciences, University of Near East , Nicosia , Northern Cyprus. 3. c Clinic of Infectious Diseases , Sisli Etfal, Educational and Research Hospital , Istanbul , Turkey. 4. d Faculty of Medicine, Department of Infectious Diseases , University of Mersin , Mersin , Turkey. 5. e Clinic of Infectious Diseases , Haydarpasa Numune, Educational and Research Hospital , Istanbul , Turkey. 6. f Faculty of Medicine, Department of Infectious Diseases , University of 19 Mayis , Samsun , Turkey. 7. g Clinic of Infectious Diseases , Samsun Educational and Research Hospital , Samsun , Turkey. 8. h Clinic of Infectious Diseases , Medeniyet University, Goztepe Educational and Research Hospital , Istanbul , Turkey. 9. i Clinic of Infectious Diseases , Umraniye Educational and Research Hospital , İstanbul , Turkey. 10. j Clinic of Infectious Diseases , Istanbul Kanuni Sultan Süleyman, Educational and Research Hospital , Istanbul , Turkey. 11. k Faculty of Medicine, Department of Infectious Diseases , University of Akdeniz , Antalya , Turkey. 12. l Clinic of Infectious Diseases , Gulhane Military Medical Academy , Istanbul , Turkey. 13. m Faculty of Medicine, Department of Infectious Diseases , University of Gaziantep , Gaziantep , Turkey. 14. n Faculty of Medicine, Department of Infectious Disease , University of Karadeniz Technical , Trabzon , Turkey. 15. o Faculty of Medicine, Department of Infectious Diseases , University of Pamukkale , Denizli , Turkey. 16. p Faculty of Medicine, Department of Infectious Diseases , University of Near East , Nicosia , Northern Cyprus. 17. q Faculty of Medicine, Department of Infectious Diseases , University of Istanbul , İstanbul , Turkey. 18. r Faculty of Medicine, Department of Infectious Diseases , University of Uludag , Bursa , Turkey.
Abstract
OBJECTIVES: Integrase strand transfer inhibitor (INSTI) is a new class of antiretroviral (ARV) drugs designed to block the action of the integrase viral enzyme, which is responsible for insertation of the HIV-1 genome into the host DNA. The aim of this study was to evaluate for the first time INSTI resistance mutations in Turkish patients. METHODS: This study was conducted in Turkey, between April 2013 and April 2015 using 169 HIV-1-infected patients (78 ARV naive patients and 91 ARV-experienced patients). Laboratory and clinical characteristics of ARV naive and ARV-experienced patients were as follows: gender (M/F): 71/7 and 80/11, median age: 38 and 38.4; median CD4(+) T-cell: 236 and 216 cells/mm(3), median HIV-1 RNA: 4.95+E5 and 1.08E+6 copies/ml. Population-based seqeunces of the reverse transcriptase, protease, and integrase domains of the HIV-1 pol gene were used to detect HIV-1 drug resistance mutations. RESULT: INSTI resistance mutations were not found in recently diagnosed HIV-1-infected patients. However, ARV-experienced patients had major resistance mutations associated with raltegravir and elvitegravir; the following results were generated:F121Y, Y143R, Q148R and E157Q (6/91 - 6.6%). CONCLUSIONS: The prevalence of INSTI resistant mutations in ART-experienced patients suggested that resistance testing must be incorporated as an integral part of HIV management with INSTI therapies.
OBJECTIVES: Integrase strand transfer inhibitor (INSTI) is a new class of antiretroviral (ARV) drugs designed to block the action of the integrase viral enzyme, which is responsible for insertation of the HIV-1 genome into the host DNA. The aim of this study was to evaluate for the first time INSTI resistance mutations in Turkish patients. METHODS: This study was conducted in Turkey, between April 2013 and April 2015 using 169 HIV-1-infectedpatients (78 ARV naive patients and 91 ARV-experienced patients). Laboratory and clinical characteristics of ARV naive and ARV-experienced patients were as follows: gender (M/F): 71/7 and 80/11, median age: 38 and 38.4; median CD4(+) T-cell: 236 and 216 cells/mm(3), median HIV-1 RNA: 4.95+E5 and 1.08E+6 copies/ml. Population-based seqeunces of the reverse transcriptase, protease, and integrase domains of the HIV-1 pol gene were used to detect HIV-1 drug resistance mutations. RESULT: INSTI resistance mutations were not found in recently diagnosed HIV-1-infectedpatients. However, ARV-experienced patients had major resistance mutations associated with raltegravir and elvitegravir; the following results were generated:F121Y, Y143R, Q148R and E157Q (6/91 - 6.6%). CONCLUSIONS: The prevalence of INSTI resistant mutations in ART-experienced patients suggested that resistance testing must be incorporated as an integral part of HIV management with INSTI therapies.
Entities:
Keywords:
DNA sequencing; Dolutegravir; Drug resistance; Elvitegravir; HIV-1 integrase; Integrase inhibitors; Raltegravir
Authors: Yiannis Koullias; Paul E Sax; Naomi F Fields; Rochelle P Walensky; Emily P Hyle Journal: Clin Infect Dis Date: 2017-10-15 Impact factor: 9.079