ABSTRACT
Background: Transmitted drug resistance (TDR) is a major challenge in the clinical management of acquired immunodeficiency syndrome (AIDS). Therefore, this study aimed to investigate the epidemic characteristics of and risk factors for human immunodeficiency virus (HIV)-1 TDR in Nanjing from 2018 to 2021 to provide support for clinical management. Methods: The HIV-1 Pol gene was amplified by nested reverse transcription polymerase chain reaction from venous blood of 1190 HIV-infected patients who did not receive antiviral therapy, and the amplified product was sequenced using an in-house sequencing method. The sequencing result was compared with the HIV drug resistance database from Stanford University to elucidate the rates of antiviral drug resistance and distribution of drug-resistant mutation sites. Factors associated with TDR were evaluated using a logistic regression model. Results: Detection of drug resistance at the gene level was successful in 1138 of 1190 HIV-1-infected patients (95.6%), and the overall 4-year drug resistance rate was 8.2% (93/1138). The drug resistance rate was higher for non-nucleoside reverse transcriptase inhibitors (NNRTIs; 6.7%) than for nucleoside reverse transcriptase inhibitors (NRTIs; 2.5%) or protease inhibitors (PIs; 0.1%) (χ 2 = 83.907, P<0.0001). The most common NNRTI-related mutation was V179D/E followed by K103N. M184V was the dominant NRTI-associated mutation, and M46L/I was the most prevalent PI-associated mutation. A CD4+ T cell count of <50 cells/µL was significantly associated with an increased risk of TDR (OR=3.62, 95% CI: 1.38-9.51, P=0.009). Conclusion: The prevalence of TDR in the city of Nanjing from 2018 to 2021 was at a moderate epidemic risk according to World Health Organization standards. Continuous monitoring of TDR can inform clinical diagnosis and treatment. Patients with advanced disease and a low CD4+ T lymphocyte count are more likely to have TDR in Nanjing.
ABSTRACT
Currently, there are limited data related to the efficacy and safety of ART regimens, as well as factors influencing immune recovery in antiretroviral therapy (ART)-naïve patients with advanced HIV infection, especially in China. We designed a single-center, retrospective cohort study from March 1, 2019, to May 31, 2022, at The Second Hospital of Nanjing, China. ART-naïve adults with advanced HIV infection (CD4+ T-cell count < 200 cells/µL) who met the study criteria were included. The plasma viral load (VL), CD4+ T-cell count, CD4/CD8 ratio, treatment discontinuation, and immune reconstitution inflammatory syndrome (IRIS) events were collected to compare the efficacy and safety of the dolutegravir (DTG) and the efavirenz (EFV) regimens. Factors of immune recovery were analyzed using the Cox regression model. Study enrolled 285 ART-naïve adults with advanced HIV-1 infection, of which 95 (33.3%) started regimens including DTG and 190 (66.7%) were treated with EFV. After ART initiation, the proportion of patients with HIV-1 RNA < 50 copies/mL was higher (22.5% versus 6.5%, P < 0.001) in those on DTG-based regimens at month 1, but no significant difference at other follow-up points. Compared to the baseline, the median CD4+ T-cell count and CD4/CD8 ratio increased significantly during follow-up both in the EFV and the DTG groups. However, the CD4+ T-cell count increased greater in patients on DTG-based regimens at months 6, 12, 24, and 36 (P < 0.05). A total of 52 (18.2%) patients discontinued treatment, with no significant difference between ART regimens in treatment discontinuation rates. Only 7 patients reported IRIS, without significant difference between ART regimens (P=0.224). Overall, 34.0% (97/285) achieved a CD4+ T-cell count ≥ 350 cells/µL during follow-up. Age (P < 0.001), baseline CD4+ T-cell count (P < 0.001), baseline VL (P < 0.001) and ART regimens (P = 0.019) were associated with the CD4+ T-cell count ≥ 350 cells/µL after adjusting for potential confounders. Among ART-naïve adults with advanced HIV infection, it appeared that DTG-based regimens were better options for initial therapy compared to regimens including EFV; in addition, ART regimens, age, baseline VL and CD4+ T-cell count were associated with immune recovery.
