Resistance-associated mutations in HIV-1 among patients failing first-line antiretroviral therapy.

Abstract

Thirty-five HIV-1 infected patients showing clinical and/or immunological failure to first line antiretroviral therapy (ART) according to WHO criteria were recruited from the ART center of Lok Nayak Hospital, New Delhi to detect the presence of resistance-mutations in reverse transcriptase (RT) and protease (PR) region of pol gene of HIV-1. Plasma viral load (PVL) was estimated. HIV-1 pol gene region encoding complete protease and reverse transcriptase (codons; 1-232 to 1-242) was reverse transcribed, followed by nested PCR. The PCR product was sequenced and analyzed. Plasma samples from 94.3% of patients with PVL >log(10) 3.0 c/mL could be amplified and analyzed. Virologic failure was detected in 65.7% of patients according to WHO criteria (PVL >log(10) 4.0). All patients were found to be infected with subtype C. One or more resistance-mutations were observed among 90.9% of study sequences. Nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations were seen among all patients, with M184V and thymidine analogue mutations (TAM) being most frequently detected (75.6% and 72.7%, respectively). Nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-mutations were detected in 63.6% of sequences, of which Y181C/I (47.6%), K103N (33.3%) and G190S (28.6%) are the most common. None of the sequences showed major protease inhibitors (PIs) resistance mutation. High prevalence of NRTI and NNRTI drug resistance mutations among the study participants warrants the use of genotypic resistance testing to prevent accumulation of resistance mutations, which would limit future treatment options.