This cross-sectional study examined the prevalence of DRMs among 3236 ART-naive patients in Qinzhou and obtained an overall PDR prevalence of 6.0% (194/3236, 95% CI: 5.1%-6.8%). According to the WHO definition of low, medium, and high levels of HIV-1 drug resistance (< 5%, 5–15% and > 15%) , PDR prevalence was at a medium epidemic level in the Qinzhou region. It was higher than the prevalence in Qinzhou in 2012–2013 (2.6%, 1/38), as well as in other regions of Guangxi . From 2014 to 2020, the overall prevalence of PDR had no downward trend in Qinzhou, Guangxi. Similarly, PDR rates are on the rise in the provinces with the most severe HIV epidemic such as Guangxi in China, similar to Dehong of Yunnan (3.48 to 9.48%)  and Liangshan of Sichuan (4.1 to 12.2%) [23, 24] from 2009 to 2017. In addition, the most common mutations of NNRTIs were E138A, K103N, and V179D mutations in this study, which was consistent with the study in a nationwide pilot survey of people with HIV/AIDS not receiving ART . The most common mutation of NRTIs is the K70K mutation, which is the same as a previous study.. The recommended first-line regimen was AZT or D4T + 3TC + NVP in China . Since 2010, D4T has been gradually replaced by AZT or TDF. Currently, the first-line therapy is TDF or AZT + 3TC + EFV or NVP, which has effectively reduced acquired drug resistance. However, with the exception of D4T, the prevalence of NNRTI PDR was 3.3% (95% CI: 2.6–3.9) in this study, which is below the 10% threshold for changing the recommended first-line antiretroviral therapy . Similarly, some studies in the past have shown that PDR is primarily driven by resistance to NNRTI, with higher resistance to EFV, NVP, and/or RPV in particular . These findings suggest that the current available first-line ART regimens containing D4T, EFV, and/or NVP and/or RPV need to be revised. In addition, it is recommended that there be drug resistance testing and viral load measurements prior to ART initiation.
PDR may be influenced by many complex factors. This exploratory study found that age is an influential factor for PDR. Compared with people aged 50 and above, young people aged 18–29 are more likely to have pre-treatment drug resistance, in line with studies in Jiangsu Province, Shandong Province, Guangxi, and Vietnam [28, 29]. The findings suggest that younger people who have an active sexual life, advocate individuality, and poor adherence to medication are more likely to transmit resistant strains to a newly infected individual. Additionally, the frequency of mutations in the subtype CRF08_BC was significantly higher than that of CRF01_AE and CRF07_BC, which was consistent with the findings in Guangxi  and in Yunnan . It has been suggested that the subtype CRF08_BC strain is more prone to base mismatches at certain sites during replication, leading to higher mutation rates, and patients carrying the CRF08_BC virus with mutations E138G, M184I, Y181C, Y188C, L100I, and may be highly resistant to antiretroviral drugs including NVP, EFV, or 3TC .
In this study, PDR did not lead to an increase in the clustering rate, as did the findings in 13 provinces or cities in China (include high and moderate prevalence regions) , Liangshan Prefecture in Sichuan  and Shijiazhuang in Hebei . Studies have suggested that the transmission capacity of resistant strains is lower than that of non-resistant strains [33, 34]. On the other hand, some of the newly diagnosed HIV-infected patients included in this study were not recently infected. They had not been treated with drugs after infection, so that the non-resistant strains became the dominant strains in the patients and drug-resistant mutations may not have been detected [35, 36]. However, there were 10 clusters containing DRMs in the genetic network of this study, and the size of clusters tend to expand with the reporting time. This result suggested that PDR may be transmitted among high-risk groups in the future, and that interventions in these populations are necessary to prevent the spread of drug-resistant strains in the region.
Our study has limitations. The sample transmission categories were based on self-reported information, and we could not confirm the authenticity of the data. We plan to conduct a more detailed study design to obtain accurate epidemiological survey data. In addition, Sanger sequencing can only detect minority drug-resistant strains at a 15%-20% frequency of HIV viral populations of patients and PDR was underestimated in this study . In the future, we hope that next-generation sequencing can be used to identify HIV drug resistant variants at frequencies as low as 0.4%.
In summary, large-scale drug resistance surveillance was carried out on HIV-infected individuals that initiated ART in Qinzhou, which has provided insights into the PDR prevalence, influencing factors, and potential transmission relationships of drug-resistant strains in the region. These findings indicate that there is an urgent need for surveillance programs of HIVDR and routine drug resistance testing in the clinical management of patients. For ART-naïve patients, the results of drug resistance monitoring could guide dosing regimens to improve the therapeutic effect. Also, behavioral intervention and traceability investigation can reduce or even block the continuous transmission of drug-resistant strains. For national institutions, large-scale studies can help develop national guidelines for ART.