Abstract
Background: Human immunodeficiency virus type 1 (HIV-1) is a major global public health concern, affecting millions worldwide. Despite significant advancements in antiretroviral therapy, the development of drug-resistant HIV-1 variants continues to challenge effective treatment. A multitude of antiretroviral drugs have been developed through intensive efforts by experts across various fields, including retrovirology, medicinal chemistry, enzymology, computational modeling, and structural biology. Objectives: This study focuses on drug-resistant mutations in protease inhibitors (PIs) and the distribution of HIV-1 subtypes in Lorestan province, Iran. Methods: A total of 59 patients were categorized into two groups: Recipients of antiretroviral therapy (ART) and drug-naive individuals. Genotypic resistance testing was performed using nested PCR, followed by sequencing and analysis of the PCR product to identify drug-resistance mutations and determine the viral subtype. Results: Among the ART recipients, 11 (78%) exhibited major mutations, while 3 (22%) had minor mutations specifically in PIs. The most commonly observed major protease inhibitor (PI) mutations were D30N (27.2%) and V32I (27.2%), followed by G48A (18.1%), L90M (18.1%), and L76V (9%). The most frequent minor PI mutations recorded were K20R (40%), L10I (20%), F53I (20%), and V11I (20%). No drug resistance was detected in drug-naive patients. Lopinavir (LPV) and nelfinavir (NFV) exhibited the highest levels of resistance, while saquinavir (SQV) and fosamprenavir (FPV) showed the highest levels of susceptibility. All participants were found to be infected with CRF35_AD, the dominant HIV-1 subtype in Iran. Conclusions: This study represents the first attempt in the region to analyze drug-resistant mutations in PIs among ART-experienced patients in Lorestan province. The findings contribute to ongoing efforts aimed at controlling the spread of drug-resistant HIV-1 strains.