Geographical and temporal trends of HIV-1 subtypes and drug resistance in China: a nationwide study over two decades (2003–2024)

<b>Objective.</b> This study aims to characterize the 20-year trends in human immunodeficiency virus 1 (HIV-1) subtypes and circulating recombinant forms (CRFs) in China, as well as patterns of transmitted drug resistance (TDR) to antiretroviral therapies commonly used in clinical practice.<b>Methods.</b> We analysed HIV-1 sequences from 81,563 individuals living in China between 2003 and 2024. Subtypes and CRFs were classified using COMET V2.4. Among these, <i>pol</i> gene sequences from 41,486 treatment-naïve individuals were used to assess TDR via the Stanford HIVdb genotypic resistance interpretation program.<b>Results.</b> Over the past two decades, CRF01_AE (43.9%) was the most prevalent HIV-1 strain in China, followed by CRF07_BC (19.0%), subtype B (12.3%), subtype C (8.4%) and CRF08_B (4.9%). However, subtype and CRF distributions varied considerably across provinces. CRF01_AE predominated in provinces such as Liaoning (92.4%), Guangxi (58.7%), Beijing (47.7%) and Hainan (44.8%), while CRF07_BC was dominant in Sichuan (63.6%), Chongqing (53.2%) and Xinjiang (82.7%). TDR analysis revealed elevated resistance to non-nucleoside reverse transcriptase inhibitors in certain provinces, including Yunnan (12.4%), Xinjiang (8.2%), Anhui (7.6%) and Henan (6.7%). In contrast, resistance to nucleoside reverse transcriptase inhibitors and integrase inhibitors remained low (<1%) across all regions. Notably, the TDR rate exceeded 5% for several regimens freely provided in China, including AZT+3TC+NVP (6.8%), AZT+3TC+RPV (8.0%), AZT+3TC+EFV (6.4%), TDF+3TC+NVP (6.0%), TDF+3TC+RPV (7.2%) and TDF+3TC+EFV (5.7%).<b>Conclusion.</b> Continued surveillance of HIV-1 genotypes and CRFs is critical, particularly in regions where routine genotypic testing is not implemented. Personalized antiretroviral regimens are urgently needed in regions with high levels of TDR.