Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naïve and treated pediatric patients.

Ravinder Singh,Dinesh Bure,Muzamil Makhdoomi,Sushil Kabra,Hilal Parray,Kalpana Luthra,Rajesh Kumar,Somi Prakash,Rakesh Lodha

doi:10.3390/v7020590

Ravinder Singh, Dinesh Bure + Show 7 more

Open Access

https://doi.org/10.3390/v7020590

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Journal: Viruses	Publication Date: Feb 10, 2015
Citations: 34	License type: CC BY 4.0

Affiliation: All India Institute of Medical Sciences

Abstract

The success of highly active antiretroviral therapy (HAART) is challenged by the emergence of resistance-associated mutations in human immunodeficiency virus-1 (HIV-1). In this study, resistance associated mutations in the reverse transcriptase (RT) and protease (PR) genes in antiretroviral therapy (ART) naïve and treated HIV-1 infected pediatric patients from North India were evaluated. Genotyping was successfully performed in 46 patients (30 ART naive and 16 treated) for the RT gene and in 53 patients (27 ART naive and 26 treated) for PR gene and mutations were identified using Stanford HIV Drug Resistance Database. A major drug resistant mutation in RT gene, L74I (NRTI), and two such mutations, K101E and G190A (NNRTI), were observed in two ART naïve patients, while M184V was detected in two ART treated patients. Overall, major resistance associated mutations in RT gene were observed in nine (30%) and seven (36%) of ART naïve and treated children respectively. Minor mutations were identified in PR gene in five children. Few non-clade C viral strains (≈30%) were detected, although subtype C was most predominant. The screening of ART naïve children for mutations in HIV-1 RT and protease genes, before and after initiation of ART is desirable for drug efficacy and good prognosis.

Highlights

The introduction of highly active antiretroviral therapy has resulted in improved treatment outcome and survival rate in human immunodeficiency virus-1 (HIV-1) infected children [1]
The successful long term viral suppression by combination antiretroviral therapy and free of cost accessibility to it has led to a considerable increase in highly active antiretroviral therapy (HAART)
Most of the current understanding about the genetic mutations in the viral genes selected by antiretroviral therapy, thereby leading to drug resistance is limited to studies on HIV-1 clade B

Summary

Introduction

The introduction of highly active antiretroviral therapy has resulted in improved treatment outcome and survival rate in HIV-1 infected children [1]. The successful long term viral suppression by combination antiretroviral therapy and free of cost accessibility to it has led to a considerable increase in highly active antiretroviral therapy (HAART). The emergence and spread of antiretroviral drug resistant HIV-1 genetic variants jeopardize the efforts to reduce the progression of HIV-1 disease and is one of the major factors responsible for therapeutic failure in HIV-1 infected children [7,8,9,10]. Most of the current understanding about the genetic mutations in the viral genes selected by antiretroviral therapy, thereby leading to drug resistance is limited to studies on HIV-1 clade B infected patients. The information on genetic mutations responsible for antiretroviral therapy(ART)

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Conclusion