The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy.

Yuncong Wang,Zhe Wang,Jia Liu,Quanbi Zhao,Hui Xing,Pengfei Ma,Jianjun Wu,Yuhua Ruan,Bin Su,Yiming Shao,Yi Feng,Lingjie Liao

doi:10.1186/1742-6405-11-36

Abstract

ObjectiveWe built a cohort study of HIV patients taking long-term first-line Antiretroviral Therapy in 2003. In this assay, we focused on the development of primary drug resistance mutations against Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), K103N, Y181C and G190A.MethodThe cohort study was built in Henan province, China. We used Single Genome Amplification (SGA) to analyze the frequency of K103N, Y181C and G190A in serial plasma samples of three individual patients. We also performed standard genotype HIV drug resistance assay in 204 patients of this cohort study to analyze the frequency of these mutations.ResultIn the SGA sequences, the K103N decreased and vanished, while the frequency of Y181C and G190A increased in individual patient receiving long-term Antiretroviral Therapy (ART). In the sequences of standard genotype HIV drug resistance assay, the frequency of K103N, Y181C and G190A had the similar pattern with that in SGA sequences. Among these patients, the viral suppression were still sufficient after receiving ART for 72 months, and 78.6% (160/204) patients could have their CD4 count over than 200cells/ul.ConclusionIn some patients, first-line ART had the possibility to provide sufficient treatment effect for over than 72 months, but in long-term treatment, the dominant NNRTI drug resistance mutation K103N could reduced, while the proportion of variants with mutation Y181C or G190A may increased. This result was not similar with that in vitro study, which state that variant with K103N or Y181C had an equal viral fitness with wild type.

Highlights

Antiretroviral therapy (ART) in China started in 2003 [1], at the end of 2011, over 350,000 Human immunodeficiency virus (HIV)-infected patients were receiving ART [2]
Nucleoside Reverse Transcriptase Inhibitor (NNRTI) is a crucial component of Chinese ART, it exhibit a longer plasma half-life and a longer duration of detectable levels than nucleoside analog reverse transcriptase inhibitors (NRTIs) [5]
Nevirapine (NVP) is an acceptable first-line NNRTI for HIV-1-infected patients [6] and is known as the most common NNRTI used in the ART regimens of China

Summary

Introduction

Antiretroviral therapy (ART) in China started in 2003 [1], at the end of 2011, over 350,000 HIV-infected patients were receiving ART [2]. Because of very limited antiretroviral drug formulations and lack of adequate laboratory monitoring of ART patients, most patients who initiated ART during the early phase of the free ART program had to stay on the same regimen for a long period of time (maximum for 112 months in my research). For this fact, the research on the development of drug resistance mutations in long-term ART became more and more necessary. All patients took NVP as NNRTI in their regimens, and were never been stopped and changed

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Conclusion