Hefei, Anhui province, is one of the cities in the Yangtze River Delta, where many people migrate to Jiangsu, Zhejiang and Shanghai. High migration also contributes to the HIV epidemic. This study explored the HIV prevalence in Hefei to provide a reference for other provinces and assist in the prevention and control of HIV in China. A total of 816 newly reported people with HIV in Hefei from 2017 to 2020 were recruited as subjects. HIV subtypes were identified by a phylogenetic tree. The most prevalent subtypes were CRF07_BC (41.4%), CRF01_AE (38.1%) and CRF55_01B (6.3%). Molecular networks were inferred using HIV-TRACE. The largest and most active transmission cluster was CRF55_01B in Hefei’s network. A Chinese national database (50,798 sequences) was also subjected to molecular network analysis to study the relationship between patients in Hefei and other provinces. CRF55_01B and CRF07_BC-N had higher clustered and interprovincial transmission rates in the national molecular network. People with HIV in Hefei mainly transmitted the disease within the province. Finally, we displayed the epidemic trend of HIV in Hefei in recent years with the dynamic change of effective reproductive number (Re). The weighted overall Re increased rapidly from 2012 to 2015, with a peak value of 3.20 (95% BCI, 2.18–3.85). After 2015, Re began to decline and remained stable at around 1.80. In addition, the Re of CRF55_01B was calculated to be between 2.0 and 4.0 in 2018 and 2019. More attention needs to be paid to the rapid spread of CRF55_01B and CRF07_BC-N strains among people with HIV and the high Re in Hefei. These data provide necessary support to guide the targeted prevention and control of HIV.

To study the characteristics of HIV pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in Hefei, a cross-sectional survey was used to collect 816 samples from newly reported HIV infections from 2017 to 2020 and 127 samples from HIV infections with virological failure from 2018 to 2019 in Hefei. HIV drug resistance levels and drug resistance mutations were interpreted using the Stanford Drug Resistance Database. Molecular networks were constructed by HIV-TRACE. Among the newly reported infections in Hefei, the prevalence of PDR was 6.4% (52/816). The drug resistance mutations were mainly V179E/D/T (12.4%), K103N (1.3%), and V106I/M (1.3%). In addition, it was found that the CRF55_01B subtype had a higher drug resistance rate than other subtypes (p < 0.05). Molecular network analysis found that K103N and V179E may be transmitted in the cluster of the CRF55_01B subtype. The prevalence of ADR among HIV infections with virological failure was 38.6% (49/127), and the drug resistance mutations were mainly M184V (24.4%), K103N/S (15.7%), Y181C (11.0%), G190S/A/E (10.2%), and V106M/I (10.2%). The molecular network was constructed by combining HIV infections with virological failure and newly reported infections; M184V and Y181C may be transmitted between them. The chi-square trend test results indicated that the higher the viral load level, the greater the number of newly reported infections linked to the infections with virological failure in the molecular network. In conclusion, interventions should focus on infections of the CRF55_01B subtype to reduce the transmission of drug-resistant strains. However, improving the treatment effect of HIV infections is beneficial for reducing the second-generation transmission of HIV.