The emergence of drug resistance among HIV-positive patients undergoing Anti- Retroviral Therapy (ART) with poor adherence to the HAART is a major concern in India. As the HIV accumulates the key mutations, the drug resistance occurs, that pose challenges to the ART regimens currently being used. Thus, the present study was carried out among the ART- naïve patients attending ART Centre at Salem district, Tamil Nadu, India. The mutations that concern the drug resistance were discriminated by determining the viral load before and after 6 months. The drug resistance was analyzed by HIV genotyping from the patients possessing a viral load of >1000 copies/mL after 6 months of ART. The mutations pertaining to drug resistance were analyzed by the online Stanford HIV Database. The 3D structures of the RT were modeled and the drugs used in the first-line regimens were docked to explore the effect of mutations on the binding pattern of the drugs. Among the 250 patients, the viral load data were obtained for 213 patients. The study found 23 patients with both virological and immunological failures and HIV drug mutations were also revealed by genotyping. The mutations of I135R/T/V/X, L178 I/M, M184V/I, D67N, K70R, and K103N were the most common among these 23 patients. The present study revealed that the NACO recommended first-line ART regimen is efficient in most of the patients attending ART center. The emergence of drug resistance of HIV variant is common even under the best circumstance of ART. This study reveals that there is a necessity for the implementation of improved and economically systematic attempt that allows the clinicians to make a rational choice of therapy regimen to overcome the first-line therapy failures among the ART- naive.
The emergence of multidrug-resistance (MDR) bacteria poses a health threat to the public. This is seen among the extended spectrum β-lactamase (ESBL) producing Enterobacteriaceae family often mediated by blaTEM and blaCTX-M genes. This study evaluates the molecular characteristics of ESBL-producing P. mirabilis isolated from Klang River, Malaysia. The physiochemical properties of the Klang River were determined. 150 water samples were collected, which 546 Gram-negative bacilli were detected. 39 (26.0%) P. mirabilis were isolated and tested against β-lactam antibiotics. 21 (53.8%) exhibited MDR, which 15 (71.4%) were ESBL-producing strains after screening with PCR and genetic sequencing approaches. Among the 15, 3 strains (20%) exhibited blaTEM gene and 12 (80%) exhibited blaCTX-M gene. Molecular docking was performed to understand the structure of the mutated β-lactamase. Findings suggest high prevalence of blaTEM and blaCTX-M genes among P. mirabilis strain isolated. There is a need of advanced molecular techniques to further elucidate MDR bacteria.
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