Analysis of mutations in the HIV-1 reverse transcriptase gene among patients receiving RT inhibitor therapy in Papua and West Papua

Abstract

The prevalence of Human Immunodeficiency Virus type 1 (HIV-1) in Papua is increasing. One of the contributing factors is antiretroviral therapy (ART) treatment failure. Mutations in the reverse transcriptase (RT) gene have been shown to alter the structure of RT, leading to resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). This study aims to identify mutations in the RT coding gene, evaluate their impact on the effectiveness of RT inhibitors, and determine the frequency of HIV resistance to RT inhibitors among people living with HIV (PLWHA) in Papua and West Papua. Analysis of mutations, resistance, and subtypes was conducted using the Stanford HIV drug resistance database. Subtype classification was validated using COMET, NCBI, and GENE2PONE. YASARA and FOLDX were used to construct RT mutant protein structures. Molecular docking was carried out using Autodock and PYRX, while visualization was performed using PyMOL and Discovery Studio. In this study, the frequency of HIV resistance among subjects was 28.57% for NRTI-only resistance and 57.14% for combined NRTI and NNRTI resistance. The most common NRTI-associated mutations were S68G, M184V, K65R, V75M, and L74I, while the most common NNRTI-associated mutations were K103N, G190A, P225H, K238T, and Y188L. The presence of these mutations altered binding affinity and molecular interactions between RT inhibitors and RT, thereby reducing the effectiveness of RT inhibitor drugs in studied population.