Drug-selective pressure effect on HIV integrase mutations in antiretroviral naïve and experienced patients

Abstract

Introduction: Resistance to antiretroviral drugs is a serious problem often related to selective drug-induced pressure and sub-optimal drug dosing. This study aimed to investigate drug resistance-associated mutations in human immunodeficiency virus type 1 (HIV-1) integrase gene caused by the drug pressure of reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). Material and methods: For this purpose, RNA of 50 HIV-infected patients (25 drug-naïve patients and 25 patients under antiretroviral therapy [INI naive]) was extracted and one step RT-nested PCR was carried out on HIV integrase (IN). Then, gene sequences were analyzed to determine sub-types and antiretroviral resistance-associated mutations (RAMs). Results: Phylogenetic analysis revealed that recombinant sub-type CRF35-AD was the most prevalent in all patients (87.2%), followed by A1 sub-type (12.8%). Among the 25 ART-experienced patients, two mutations (N155I, G163R) associated with resistance to integrase inhibitors (INI) were found. Among the 25 naïve patients, several polymorphisms were observed, which was also lower in this group than in the ART group. Conclusions: The results of this study indicated that the integrase mutations can be caused by the effect of selective pressure induced by antiviral agents, such as RTIs and PIs. Therefore, examination of the integrase drug resistance mutations is recommended before starting treatment in Iran.