High rate of mutation K103N causing resistance to nevirapine in Indian children with acquired immunodeficiency syndrome

Abstract

In north India the number of paediatric cases with acquired immunodeÞ ciency syndrome (AIDS) is on the rise. Most drug combinations used for treatment of AIDS incorporate nevirapine, resistance to which develops very fast if given singly or because of unplanned interruptions. This paper investigates presence of mutations at codon 103 and codon 215 of the HIV pol gene causing resistance to nevirapine and zidovudine (AZT) respectively in 25 children with AIDS. Mutations T215Y and K103N were detected by a nested cum ampliÞ cation refractory mutation system polymerase chain reaction (ARMS PCR) and the results were conÞ rmed by direct sequencing in Þ ve randomly selected cases. Nineteen patients had received nevirapine containing regimen and six were drug naive. Mutation K103N was observed in 56% (14/25) of the children while mutation T215Y was found in none. Two of the six drug naïve children also showed K103N mutation. Thus, Indian children drug naïve or treated with nevirapine containing regimens show a high rate of mutation conferring resistance to nevirapine which calls for a judicious use of nevirapine both in antenatal and postnatal setting.

High viremia and low level of transmitted drug resistance in anti-retroviral therapy-naïve perinatally-infected children and adolescents with HIV-1 subtype C infection

“…Other paediatric studies from India have revealed similar low TDRM prevalence; among a south Indian cohort of 48 perinatally infected children of mean age 5.7 years, none had major drug resistance mutations [27]. In another study from north India where 25 ART-naïve children with mean age 6 years were studied, K103N was the only drug resistance mutation that was observed [28]. Studies on ART-naïve adults from different parts of India with sample sizes ranging from 34 to 107 patients, have revealed low TDRM prevalence (<5%) [11,12,14-18].…”

Multimethod Longitudinal HIV Drug Resistance Analysis in Antiretroviral-Therapy-Naive Patients

“…In Thailand, a duplex ARMS-PCR assay was successfully applied to detect K103N/Y181C and Q151M/ T215Y mutations in 45 naive and treated HIV-1 CRF01_AE-infected patients that achieved good performance ratings (96% sensitivity and 98% specificity) similar to those of Sanger sequencing (60). The suitability of ARMS-PCR was also demonstrated in two studies carried out in India that screened 60 individuals for mutations at codons 70, 184, and 215 (43) and 25 children for mutations at codons 103 and 215 (44). The good performance of ARMS-PCR comes with a fast turnaround time and low cost but has the limitation of providing information on only select mutations.…”

“…They have been developed as an alternative for genotyping assays, among which amplification-refractory mutation system (ARMS)-PCR uses the difference in extension efficiency between primers with matched and mismatched 3= bases to identify mutations based solely on the presence of PCR products via gel electrophoresis. ARMS-PCR was developed in 1989 and was further optimized by our group and others to identify HIVDR mutations with high performance compared to that of standard sequencing (39)(40)(41)(42)(43)(44). So far, no study has compared point mutation assays with NGS.…”

Genotypic HIV type-1 drug resistance among patients with immunological failure to first-line antiretroviral therapy in south India

“…In India, studies of drug resistance have identified a maximum frequency of 81% among treated patients [8,9] and 56% among the paediatric population [10], although these studies had small sample sizes and identified resistance at virological failure that does not reflect the current scenario. Here, we present the frequency and pattern of resistance mutations to reverse transcriptase (RT) inhibitors among patients receiving first-line treatment who developed confirmed immunological failure (IF).…”