Evolutionary Emergence of HIV ‐1 Subtype G and Subtype‐Linked Transmitted NNRTI Resistance Among HIV Patients in Oman

Background This study aimed to characterize HIV‐1 subtype distribution and transmitted drug resistance (TDR) patterns among treatment‐naïve individuals in Oman to inform evidence‐based treatment guidelines and molecular surveillance strategies. Methods A nationwide retrospective cross‐sectional study was conducted to analyse HIV‐1 pol gene sequences from all newly diagnosed, treatment‐naïve individuals in Oman over a nine‐year period. A total of 963 treatment‐naïve individuals diagnosed with HIV‐1 infection between 2016 and 2024 were included in this nationwide retrospective analysis. Partial pol gene sequences encompassing protease and reverse transcriptase regions were amplified and sequenced. Subtyping was performed using multiple computational tools (COMET, RIP and jpHMM) with phylogenetic confirmation using maximum‐likelihood methods. Drug resistance mutations were interpreted using the Stanford HIV Drug Resistance Database (version 9.5). Results Subtype G was the predominant lineage (38.2%, n = 368), followed by subtype A1 (28.0%, n = 270), CRF01_AE (11.7%, n = 113), and subtype C (7.4%, n = 71). Sixty‐four other recombinant strains were identified, including three novel CRFs candidates. Subtype A1 exhibited the highest resistance burden (21.1%, n = 57), primarily associated with the K103N substitution, whereas subtype G remained largely susceptible (96.2%, n = 354). Overall, 13.0% ( n = 125) harboured at least one NNRTI resistance mutation under the ≥ 15 threshold. No major resistance mutations were detected against nucleoside reverse transcriptase inhibitors (NRTIs), including tenofovir, emtricitabine, and lamivudine. Conclusions The Omani HIV‐1 epidemic is characterized by subtype G dominance, subtype‐specific resistance patterns, and identification of putative novel circulating recombinant forms (CRFs). The high NNRTI resistance burden (13.0%) supports prioritizing INSTI‐based regimens. Continuous molecular surveillance is essential for monitoring emerging resistance.