Integrase (IN) is an important enzyme for the replication of the type-1 human immunodeficiency virus (HIV- 1), and an essential target for the development of anti-HIV drugs. The enzyme is currently targeted by first and secondgeneration inhibitors [raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG)]. Of these, resistance to RAL and EVG are associated with three main pathways involving key mutations at positions N155H, Q148K/R/H, and Y143R/C within the IN gene. Although new resistance mutations appear to confer only low levels of cross-resistance to secondgeneration drugs (DTG), the Q148 pathway with numerous secondary mutations has the potential to significantly decrease susceptibility to all inhibitors of IN. In order to get insights into the development of IN resistance to first and second generation inhibitors using in silicoapproaches, in this study, one of the clinically essential mutant (MT)-Q148R of IN was modeled and docked with inhibitors. The MT model was built using the template and wild type (WT) 4E1M of HIV-1 integrase. Docking results indicate that in MT-Q148R the score was lower with respect to all inhibitors in comparison to the WT. In this study, the MT-Q148R of IN from HIV-1 displayed low affinity, this could be attributed to less number of interactions principally hydrogen and halogen bonds with the inhibitors (DTG, EVG and RAL), compared to the WT. Therefore, it can be suggested that the MT could not bind efficiently with inhibitors owing to its structural changes due to substitution to mediate its inhibitory activity and eventually leads to DTG, EVG and RAL resistance.