The goal of this study was to assess risk factors associated with HIV/AIDS progression. Between May 2007 and December 2014, 114 subjects were enrolled in Wuxi City and examined every 6 months. The pol gene sequence was amplified to ascertain the HIV-1 subtype. A Cox proportional hazards regression model was used to estimate the factors associated with HIV/AIDS progression. The median follow-up time for all 114 subjects was 26.70 months (IQR: 18.50-41.47), while the median progression time of the 38 progressed subjects was 24.80 months (IQR: 14.13-34.38). Overall, the CRF01-AE subtype was correlated with a significant risk of accelerated progression compared to non-CRF01-AE subtypes (HR = 3.14, 95%CI: 1.39-7.08, P = 0.006). In addition, a lower CD4 count (350-499) at baseline was associated with a risk of accelerated HIV/AIDS progression compared to higher CD4 count (≥500) (HR = 4.38, 95%CI: 1.95-9.82, P < 0.001). Furthermore, interaction analyses showed that HIV-1 subtypes interacted multiplicatively with transmission routes or CD4 count at baseline to contribute to HIV/AIDS progression (P = 0.023 and P < 0.001, respectively). In conclusion, the CRF01-AE subtype and a lower CD4 count at baseline tend to be associated with the faster progression of HIV/AIDS. Understanding the factors affecting HIV/AIDS progression is crucial for developing personalized management and clinical counselling strategies.