Abstract

The use of antiretroviral therapy has reduced rates of mortality and morbidity in patients with human immunodeficiency virus/acquired immune deficiency syndrome(HIV/AIDS). However, transmission of drug-resistant strains poses a challenge to control the spread of HIV-1. Primary resistance to integrase strand-transfer inhibitors (INSTIs) is rare despite their increased use. The prevalence of transmitted drug resistance (TDR) to INSTIs was 0.9% in northern Taiwan. This study was to analyse the prevalence and risk factors of TDR to INSTIs in southern Taiwan. In this study, we enrolled antiretroviral treatment-naïve HIV-1-infected subjects who underwent voluntary counselling and testing from 2013 to 2016 in southern Taiwan. Genotypic drug resistance, coreceptor tropism (CRT) and INSTI resistance were determined. Logistic regression was used to analyse the risk factors for INSTI polymorphic substitution. Sequences were obtained from 184 consecutive individuals, of whom 96.7% were men who have sex with men and 3.3% were heterosexual. Of the patients, 10% (19/183) had hepatitis B and 33.3% (61/183) had syphilis infection. Subtype B HIV-1 strains were found in 96.1% of the patients. Fifteen patients (8.4%, 15/178) harboured nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors or protease inhibitors resistance. CCR-5 coreceptors were used by 71.4% (130/184) of the patients. None of the patients had INSTI resistance-associated mutations, however 16 patients had INSTI polymorphic substitutions, and they were associated with a higher HIV viral load (p = 0.03, OR 2.4, CI 1.1–5.3) and syphilis infection (p = 0.03, OR 3.7, CI 1.1–12.0). In conclusion, no signature INSTI resistance-associated mutations were detected in our cohort. Continued monitoring of TDR to INSTI is needed due to the increased use of INSTIs.

Highlights

  • Transmitted drug resistance (TDR) can reduce the treatment options available to newly HIV-1 infected patients, and it is associated with an increased risk of virological failure [1]

  • Surveillance of transmitted drug resistance (TDR) in Taiwan has revealed the impact of improved antiretroviral therapy (ART) regimens, routine pre-treatment genotypic drug resistance testing (GRT) in ART-naïve patients is not conducted in Taiwan due to financial constraints

  • The main aim of this study was to analyse the prevalence of TDR to integrase strandtransfer inhibitors (INSTIs) in HIV-1 infected patients recruited from our voluntary counselling and testing (VCT) program in southern Taiwan, and to identify risk factors for its occurrence

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Summary

Introduction

Transmitted drug resistance (TDR) can reduce the treatment options available to newly HIV-1 infected patients, and it is associated with an increased risk of virological failure [1]. Surveillance of TDR in Taiwan has revealed the impact of improved antiretroviral therapy (ART) regimens, routine pre-treatment genotypic drug resistance testing (GRT) in ART-naïve patients is not conducted in Taiwan due to financial constraints. The integrase inhibitors raltegravir, dolutegravir and elvitegravir are increasingly www.oncotarget.com used as first-line ART in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) [5, 6]. Raltegravir was approved for clinical use in ART-experienced patients in 2009, and in 2012 it was approved for use in ARVnaive patients when used in combination with two NRTIs. Dolutegravir was approved as a first-line single tablet regimen (coformulated with abacavir/lamivudine) in June 2016 for treatment-naïve HIV-1 infected patients in Taiwan

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