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; Mao-Song Tsai; Chia-Jui Yang; Shu-Hsing Cheng; Hsin-Yun Sun; Shu-Fang Chang; Li-Hsin Su; Yi-Ching Su; Chien-Ching Hung; Sui-Yuan Chang

doi:10.2147/IDR.S158341

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

Infect Drug Resist. 2018 Jun 5:11:849-859. doi: 10.2147/IDR.S158341. eCollection 2018.

Authors

Chien-Yu Cheng^{1

2}, Mao-Song Tsai³, Chia-Jui Yang^{3

4}, Shu-Hsing Cheng^{1

5}, Hsin-Yun Sun⁶, Shu-Fang Chang⁷, Li-Hsin Su⁷, Yi-Ching Su⁶, Chien-Ching Hung^{6

8

9

10}, Sui-Yuan Chang^{7

11}

Affiliations

¹ Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan.
² School of Public Health, National Yang-Ming University, Taipei, Taiwan.
³ Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
⁴ School of Medicine, National Yang-Ming University, Taipei, Taiwan.
⁵ School of Public Health, Taipei Medical University, Taipei, Taiwan.
⁶ Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
⁷ Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
⁸ Department of Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan.
⁹ Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
¹⁰ China Medical University, Taichung, Taiwan.
¹¹ Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Abstract

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: RAM; antiretroviral therapy; genotypic resistance; nNRTIs; population sequencing; treatment guidelines; virological failure.