The frequency of HIV-I drug resistance mutations among treatment-naïve individuals at a tertiary care centre in south India

Abstract

Antiretroviral treatment (ART) use in India requires information on baseline drug resistance mutations and polymorphisms in the protease (Pr) and reverse transcriptase (RT) genes of HIV-1 strains from treatment-naïve individuals. We report resistance predictor mutations and polymorphisms in the Pr and the RT sequence of non-clade B HIV-1 strains from ART naïve individuals. The genotypic resistance assay was done on 93 treatment-naïve individuals. The sequences were analysed by Stanford HIV drug resistance data for genotypic drug resistance analysis and REGA HIV-1 subtyping tool. Phylogenetic tree was generated with MEGA 4 for quality control. Ninety-two strains belonged to clade C and one to clade A (A1). Amino acid substitutions were seen at positions associated with drug resistance in Pr gene--10, 24, 74 (each 3%) and position 82 (11%). Substitutions were seen at positions 41 (1%), 100 (1%), 101 (6%), 103 (2%), 179 (6%) and 181 (1%) of the RT sequence known to confer drug resistance in clade B. Polymorphisms in HIV-1 pol gene among treatment-naïve individuals were similar when compared with previous data. One strain each had Y181C substitution, T74S and E35G substitutions in the Pr and one had A98G, K101R and L210FL substitutions in RT.

Zero prevalence of primary drug resistance-associated mutations to protease inhibitors in HIV-1 drug-naive patients in and around Aligarh, India

“…This mutation affects the conformational equilibrium between the closed and semi-open conformations of the free protease. It has been postulated that an E35D mutation reduces interaction with HLA B44, thus evading immune response as well conferring resistance [3]. L63P mutation strongly enhances viral replicative fitness in the presence of some ART drugs [25]; it was observed in 32 (61.5%) patients.…”

“…It has been estimated that approximately 2.31 million people are living with HIV/AIDS in India [2] and nearly 9.7 million people are receiving anti-retroviral therapy (ART) in low-and middle-income countries by the end of 2012 as per UNAIDS global report 2013. ART is the best and only option to reduce morbidity and mortality associated with HIV infection [3]. A major obstacle to the long-term efficacy of ART is the emergence of drug resistance mutations in the polymerase gene of HIV-1, which reduces the susceptibility of the gene to anti-retroviral (ARV) drugs [4].…”

Drug Resistant Mutations Detected by Genotypic Drug Resistance Testing in Patients Failing Therapy in Clade C Hiv-1 Infected Individuals From India

“…Amplification and sequencing of the Pr and RT genes and was carried out as previously described. [8] All the sequences were also submitted to the calibrated population resistance tool (CPR) available at the Stanford HIV drug resistance database. Information on the frequency of mutations observed in our strains was generated based on the drug resistance mutation list of the IAS-USA major (2007).…”

Different Effects of Nonnucleoside Reverse Transcriptase Inhibitor Resistance Mutations on Cytotoxic T Lymphocyte Recognition between HIV-1 Subtype B and Subtype A/E Infections

“…Drug treatment often increases the risk of subsequent transmission of drug resistance in new cases of an HIV infection. The Y181C mutation was also reported in treatment-naive individuals among different cohorts (see Table S1 in the supplemental material) at 2.3% (1/43), 1.1% (1/91), 0.6% (1/156), 3.0% (3/101), and 1.6% (2/129) of treatment-naive subtype C-infected individuals in Mozambique (42), in South India (43), in KwaZulu-Natal Provinces in South Africa (44), in Tanzania (45), and in China (46), respectively, and 0.43% of 1,389 treatment-naive individuals in southern Vietnam, where subtype A/E virus was the most prevalent subtype (47). The Y181C mutation or the Y181C/I mutation was detected in 0.4%, 0.3% (1/303), 0.2% (4/2,655), and 1.8% (6/336) of treatment-naive individuals in northern Poland (48), Brazil (49), Mexico (50), and Hondurans (51), respectively, where subtype B was the most prevalent.…”