长沙地区307例新确诊HIV-1感染者原发耐药突变情况及完全活性ART方案治疗效果

Analysis of primary drug resistance mutations among 307 newly diagnosed HIV-1-infected individuals in Changsha and the treatment outcome of fully active ART regimen

目的 观察长沙地区人类免疫缺陷病毒1型(HIV-1)感染者原发耐药突变(PDRM)情况,以及具有完全活性的抗逆转录病毒治疗(ART)方案对PDRM的治疗效果。方法 纳入长沙地区新确诊的HIV-1感染者307例,收集患者人口学特征等数据,采集血浆检测CD4+T淋巴细胞计数、HIV-1 RNA病毒载量及基因型耐药检测,判断患者PDRM情况。PDRM患者根据基因型耐药检测结果给予具有完全活性的ART方案;非PDRM患者采用我国指南推荐初治ART方案。比较PDRM患者和非PDRM患者的临床特征、治疗方案和治疗结局,采用Kaplan-Meier法比较PDRM与非PDRM患者的预后。结果 307例HIV-1感染者中,PDRM 77例,非PDRM 230例。PDRM患者中,单个耐药突变位点67例、多个耐药突变位点10例,V179D和V179E是最常见的耐药突变位点。PDRM患者与非PDRM患者的HIV-1亚型分布比较差异有统计学意义(P<0.01)。ART方案主要为非核苷酸逆转录酶抑制剂(NNRTI)+2种核苷酸逆转录酶抑制剂(NRTI),PDRM患者与非PDRM患者的ART方案比较差异有统计学意义(P<0.05)。PDRM患者病毒学抑制率持续低于非PDRM患者,平均生存时间较非PDRM患者缩短(P均<0.01)。结论 长沙地区HIV-1感染者当前PDRM主要针对NNRTI及NRTI药物,PDRM患者更易在治疗早期发生病毒学不良事件,需要推广含整合酶抑制剂类药物的完全活性ART方案以便尽早降低病毒载量,改善患者预后。

Objective To observe the status of primary drug resistance mutation(PDRM)among human immunode⁃ficiency virus type 1(HIV-1)-infected individuals in Changsha and the treatment outcome of fully active antiretroviral ther⁃apy(ART)regimen on PDRM.Methods Totally 307 newly diagnosed HIV-1-infected individuals were collected,and demographic characteristics and other data were gathered.Plasma samples were collected for CD4+T lymphocyte count,HIV-1 RNA viral load,and genotypic drug resistance testing to determine the PDRM of patients.Patients with PDRM were given fully active ART regimens based on genotypic drug resistance testing results.Patients without PDRM adopted the ini⁃tial ART regimens recommended by Chinese HIV/AIDS guidelines.We compared the clinical characteristics,treatment regimens and treatment outcome of patients with and without PDRM.Meanwhile,Kaplan-Meier analysis was used to com⁃pare the prognosis between patients with and without PDRM.Results Among 307 HIV-1-infected individuals,there were 77 patients with PDRM,and 230 patients without PDRM.Among patients with PDRM,67 cases had a single drug re⁃sistance mutation,while 10 cases had multiple drug resistance mutations.V179D and V179E were the most common drug resistance mutations.There was a statistically significant difference in the distribution of HIV-1 subtypes between patients with and without PDRM(P<0.01).The ART regimen mainly consisted of non-nucleotide reverse transcriptase inhibitors (NNRTI) and two types of nucleotide reverse transcriptase inhibitors (NRTI). The difference in ART regimen between pa⁃ tients with and without PDRM was statistically significant (P<0. 05). The virological suppression rate in patients with PDRM remained consistently lower than that patients without PDRM, and the mean survival time was shorter than that of patients without PDRM (both P<0. 01). Conclusions In Changsha,the current PDRM mainly targets NNRTI and NRTI drugs, and patients with PDRM are more prone to develop virological adverse events in the early stages of treatment. There⁃ fore, it is necessary to promote the application of fully active ART regimen in this population to reduce viral load as soon as possible and to achieve better prognosis for patients.