欢迎来到《四川大学学报(医学版)》

艾滋病住院初治患者HIV-1基因亚型及传播性耐药现状分析

Analysis of HIV-1 Subtypes and Transmitted Drug Resistance in Hospitalized Treatment-Native Patients With AIDS

  • 摘要:
    目的 分析感染科艾滋病住院初治患者HIV-1基因亚型分布特征、传播性耐药(transmitted drug resistance, TDR)现状及其影响因素。
    方法 纳入2020年1月–2022年12月期间在成都市公共卫生临床医疗中心感染科住院并确诊的初治艾滋病患者,收集患者抗病毒治疗(antiretroviral therapy, ART)前的血液样本,采用in-house法进行HIV基因扩增、测序,系统进化树分析HIV-1基因亚型,HIV耐药数据库在线比对分析耐药突变位点、耐药种类、耐药程度,进行HIV-1基因亚型分布特征和TDR发生情况及其影响因素分析。
    结果 共收集213例患者的血样,HIV基因扩增成功率83.10%(177/213),共检出10种基因亚型,以CRF07_BC最常见(43.50%,77/177),其次为CRF01_AE(37.85%),独特重组亚型(unique recombinant forms, URFs)较少(8.47%),其他亚型10.17%;这4种HIV-1基因亚型仅在不同年龄的分布差异有统计学意义(P=0.024),进一步分析发现仅CRF01_AE和URFs在年龄为30~50岁和年龄>50岁的分布差异有统计学意义,URFs在年龄为30~50岁人群占比较高(P=0.008)。CRF07_BC、CRF01_AE、URFs、其他亚型耐药发生率分别为6.49%、8.96%、13.33%、5.56%,差异无统计学意义(P>0.05);TDR总发生率6.57%,非核苷类逆转录酶抑制剂(non-nucleoside reverse transcriptase inhibitors, NNRTIs)TDR发生率5.16%,突变位点主要为V179D/E、E138A/G、V106M/I、Y181C,核苷类逆转录酶抑制剂(nucleoside reverse transcriptase inhibitors, NRTIs)TDR发生率1.88%,突变位点主要为M184V,1例患者发生NNRTIs、NRTIs双重耐药;4.23%高度耐药,0.47%中度耐药,1.88%低度耐药;本研究未发现TDR在不同年份、人口学特征、感染途径、基线状况、机会性感染方面的差异有统计学意义(P>0.05)。
    结论 艾滋病住院初治患者HIV-1基因亚型复杂、多样,TDR总发生率较高,需加强TDR监测,以优化ART治疗、减少耐药传播。

     

    Abstract:
    Objective To investigate the distribution characteristics of HIV-1 subtypes, the status of transmitted drug resistance (TDR), and the influencing factors of TDR in treatment-naive patients with AIDS who are hospitalized.
    Methods Treatment-naive patients with AIDS who were admitted to the Infectious Disease Department, Public Health Clinical Center of Chengdu between January 2020 and December 2022 were enrolled in the study. The diagnosis and confirmation diagnosis of all the subjects were made at the same hospital. Blood samples were collected from the subjects before antiretroviral therapy (ART). The in-house method was used for HIV gene amplification and sequencing. A phylogenetic tree was constructed to analyze the HIV-1 subtypes. The Stanford HIV Drug Resistance Database was used to conduct an online comparative analysis of the drug resistance mutation sites and to determine the types and levels of drug resistance. The distribution characteristics of HIV-1 subtypes, the occurrence of TDR, and the influencing factors of TDR were analyzed.
    Results A total of 213 patients were included in the study and their blood samples were collected. HIV-1 subtypes were successfully amplified in 83.10% (177/213) of the subjects. Ten HIV subtypes were identified, with CRF07_BC being the most common subtypes, accounting for 43.50% (77/177), which was followed by CRF01_AE at 37.85%. Unique recombinant forms (URFs) were relatively uncommon, accounting for 8.47%. The other subtypes accounted for 10.17%. These 4 categories of HIV-1 subtypes were distributed with statistically significant differences in different age groups (P=0.024). Further analysis revealed significant differences in the distribution of the HIV-1 subtypes of CRF01_AE and URFs between the groups of patients aged 30-50 years and those over 50. In addition, URFs accounted for a higher proportion in patients aged 30 to 50 years (P=0.008). The incidences of TDR were 6.49%, 8.96%, 13.33%, and 5.56% for CRF07_BC, CRF01_AE, URFs, and other subtypes, respectively, showing no significant difference (P>0.05). The overall TDR was 6.57%. The TDR for non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 5.16%, and the main mutation sites were V179D/E, E138A/G, V106M/I, and Y181C. The TDR for nucleoside reverse transcriptase inhibitors (NRTIs) was 1.88%, and the main mutation site was M184V. One patient was found to be resistant to both NNRTIs and NRTIs. The highly resistant rate was 4.23%, moderate resistance was 0.47%, and low resistance was 1.88%. No significant effects of the specific years, demographic characteristics, transmission route, baseline condition, and opportunistic infections on TDR were found in this study (P>0.05).
    Conclusions The HIV-1 subtypes are diverse and complex in treatment-naive patients with AIDS who were hospitalized. The overall prevalence of TDR is relatively high. It is necessary to strengthen HIV drug resistance testing to optimize ART treatment and reduce the risk of drug resistance transmission.

     

/

返回文章
返回