Baseline HIV Genotyping and Antiretroviral Therapy Resistance Mutations in Saudi Arabian Population, a Multicentre, Cross-Sectional Study

Background: Transmitted drug resistance (TDR) remains a critical challenge in HIV-1 management, particularly in treatment-naïve populations. Baseline genotypic resistance testing is recommended to optimize antiretroviral therapy (ART), yet data from Saudi Arabia remain limited. This study aimed to characterize HIV-1 genetic diversity and baseline resistance-associated mutations among newly diagnosed, ART-naïve individuals. Methods: We conducted a multi-centre, retrospective cross-sectional study across three hospitals in Saudi Arabia between January 2023 and December 2024. Adult, treatment-naïve patients with confirmed HIV infection who underwent genotyping using Sanger sequencing were included. Mutations in reverse transcriptase (RT), protease (PI), and integrase (INSTI) genes were analyzed using the Stanford HIV Drug Resistance Database. Demographic, clinical, and virological data were collected, and comparative analyses between regions were performed. Results: A total of 614 patients were included, predominantly male (85.5%) and aged 25–44 years. Most patients presented with high viral loads (≥10,000 copies/mL, 89.7%), and 25.3% had CD4 counts <200 cells/mm3. HIV-1 subtype distribution was highly diverse, with subtype C (19.5%), CRF02_AG (15.6%), and subtype G (12.7%) predominating. Although mutations were frequently detected (RT: 85.2%, PI: 94.7%, INSTI: 36.4%), the majority were subtype-associated polymorphisms rather than major drug resistance mutations. Clinically significant mutations including M184V/I (1.17%), K103N (0.83%), and K65R (0.17%) were observed at low frequencies. No major INSTI resistance mutations were detected. Multi-class mutation patterns were common but largely driven by accessory variants. Conclusions: Despite the high prevalence of detected mutations, clinically significant TDR remained low, occurring in approximately 2.8% of patients. Most detected variants were polymorphic or accessory mutations, while susceptibility to INSTIs remained largely preserved. Continued baseline genotyping and molecular surveillance remain important to monitor emerging resistance patterns.