Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study

Abstract

Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study Chien-Yu Cheng,1,2 Mao-Song Tsai,3 Chia-Jui Yang,3,4 Shu-Hsing Cheng,1,5 Hsin-Yun Sun,6 Shu-Fang Chang,7 Li-Hsin Su,7 Yi-Ching Su,6 Chien-Ching Hung,6,8–10 Sui-Yuan Chang7,11 For the Taiwan HIV Study Group 1Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan; 2School of Public Health, National Yang-Ming University, Taipei, Taiwan; 3Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; 4School of Medicine, National Yang-Ming University, Taipei, Taiwan; 5School of Public Health, Taipei Medical University, Taipei, Taiwan; 6Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; 7Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan; 8Department of Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan; 9Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; 10China Medical University, Taichung, Taiwan; 11Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan Background: Increasing trends of resistance-associated mutations (RAMs) to non-nucleoside reverse-transcriptase inhibitors (nNRTIs) have raised concerns about the effectiveness of the regimens in the national HIV treatment programs in resource-limited countries. We aimed to retrospectively investigate the incidence and patterns of emergent RAMs of HIV-1 in HIV-positive adults experiencing virological failure to first-line nNRTI-containing combination antiretroviral therapy (cART) in Taiwan. Patients and methods: Between June 2012 and March 2016, 1138 antiretroviral-naïve HIV-positive adults without baseline RAMs who initiated nNRTI-containing regimens were included for analysis. Virological failure was defined as plasma viral load (PVL) ≥200 copies/mL after 6 months of cART or confirmed PVL ≥200 copies/mL after achieving PVL <50 copies/mL. Population sequencing was retrospectively performed to detect baseline and emergent RAMs. RAMs were interpreted using the International AIDS Society-USA 2016 mutations list. Results: Seventy-one patients (6.2%) developed virological failure, which occurred in 14.8% (43/291), 3.9% (26/675), and 1.2% (2/172) of patients receiving 2 nucleoside reverse-transcriptase inhibitors (NRTIs) plus nevirapine, efavirenz, and rilpivirine, respectively. Among those, 53 (74.6%) had emergent RAMs identified, which included 43 (81.1%), 53 (100.0%), and 1 (1.9%) with RAMs to NRTIs, nNRTIs, and protease inhibitors, respectively; and 43 (81.1%) had multi-drug resistance. The most common emergent RAMs to NRTIs were M184V/I (42.3%) and K65R (28.2%), and those to nNRTIs were Y181C (42.3%), K103N (15.5%), G190A/E/Q (12.7%), V179D/E (12.7%), and V108I (9.9%). Conclusion: While the rates of virological failure varied with the nNRTI used, the rate of emergent RAMs of HIV-1 to NRTIs and nNRTIs among the antiretroviral-naïve patients who failed nNRTI-containing cART remained low. Keywords: antiretroviral therapy, treatment guidelines, virological failure, genotypic resistance, population sequencing, nNRTIs, RAM