Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, 610041, Sichuan, China.
BMC Infect Dis. 2022 Jul 7;22(1):602. doi: 10.1186/s12879-022-07576-z.
Sichuan province is one of the highest AIDS epidemic provinces in China, with a large number of floating population. The annual number of cases of HIV/AIDS reported in Sichuan has been the highest province in China for several successive years. There is a lack of widespread and representative data on the distribution of HIV genotypes in Sichuan. We aim to investigate the characteristics of HIV-1 molecular epidemiology and transmitted drug-resistance in newly diagnosed HIV-infected patients in Sichuan, China.
Archived plasma samples (n = 1524) from HIV-1 newly-diagnosed individuals in April 2019 were selected by cross-sectional investigation from all 21 cities in Sichuan province. Phylogenetic relationship, transmission cluster, and genotypic drug resistance analyses were performed using HIV-1 polymerase (pol) gene sequences. We also analysed the association of demographic and virological factors with transmitted drug-resistance (TDR) and transmission clusters.
Partial pol gene sequences were obtained from 1297 cases. HIV-1 epidemic strains in Sichuan province: the majority of genotypes were circulating recombinant form (CRF) 07_BC (675, 52.04%), CRF01_AE (343, 26.45%), CRF08_BC (115, 8.87%), CRF85_BC (67, 5.17%), subtype B (33, 2.54%), the other genotypes only accounted for 4.93%, and unique recombinant forms (URFs) (23, 1.77%) were observed in the study, and the difference of age, ethnicity, education, occupation, region and transmission pathway of different genotypes were statistically significant. According to WHO HIVDR surveillance threshold, the level of TDR has reached a medium level, with 72 of 1297 (5.55%) cases carrying drug-resistance mutation sites, TDR mutation frequency to nonnucleoside reverse transcriptase inhibitors (NNRTIs, 3.85%) was much higher than nucleoside reverse transcriptase inhibitors (NRTIs, 0.31%) and protease inhibitors (PIs, 1.70%), and CRF08_BC was a risk factor for TDR (odds ratio, 8.32; 95% CI 4.38-15.80 for CRF07_BC, P < 0.05). The most common drug resistance HIV-1 mutation pattern for NNRTI was V106 (1.31%, 17/1297) and E138 (1.16%, 15/1297), and for PI was M46 (0.69%, 9/1297). A total of 205 (15.8%) pol sequences were involved in the genetic transmission network clusters, CRF01_AE (odds ratio, 2.369; 95% CI 1.659-3.382; P < 0.05), subtype B (odds ratio, 13.723; 95% CI 6.338-29.71; P < 0.05), drug resistance (odds ratio, 0.306; 95% CI 0.106-0.881; P < 0.05) and different levels of education (P < 0.05) were significantly associated to be in clusters.
The distribution of HIV-1 genotypes in Sichuan is more diverse and complex, and the Men who have sex with men (MSM) is underrated, arguing for behavior scaling up intervention in this specific population besides the elderly people with heterosexual transmission risk groups. The risk of TDR mutation frequency increased in newly diagnosed patients highlights the significance of genotypic drug resistance monitoring and molecular surveillance of pretreatment HIV-1 drug resistance. The regimen composed of TDF, 3TC and EFV was still currently the preferred solution used free first-line therapy.
四川省是中国艾滋病疫情最高的省份之一,流动人口众多。四川省每年报告的艾滋病病毒/艾滋病病例数连续多年位居全国之首。目前,四川省 HIV 基因型的分布情况缺乏广泛而具有代表性的数据。本研究旨在调查中国四川省新诊断 HIV 感染患者中 HIV-1 分子流行病学和传播耐药的特征。
通过横断面调查,从四川省 21 个城市中选取了 2019 年 4 月新诊断的 1524 例 HIV-1 感染者的存档血浆样本。利用 HIV-1 聚合酶(pol)基因序列进行系统进化关系、传播簇和基因型耐药分析。我们还分析了人口统计学和病毒学因素与传播耐药(TDR)和传播簇的相关性。
获得了 1297 例部分 pol 基因序列。四川省 HIV-1 流行株:主要基因型为重组型循环(CRF)07_BC(675 例,占 52.04%)、CRF01_AE(343 例,占 26.45%)、CRF08_BC(115 例,占 8.87%)、CRF85_BC(67 例,占 5.17%)、B 亚型(33 例,占 2.54%),其他基因型仅占 4.93%,研究中观察到独特重组形式(URFs)(23 例,占 1.77%),不同基因型在年龄、种族、教育程度、职业、地区和传播途径方面存在统计学差异。根据世卫组织 HIVDR 监测阈值,TDR 水平已达到中等水平,1297 例中有 72 例(5.55%)携带耐药突变位点,核苷逆转录酶抑制剂(NRTIs,0.31%)耐药突变频率明显低于非核苷逆转录酶抑制剂(NNRTIs,3.85%)和蛋白酶抑制剂(PIs,1.70%),CRF08_BC 是 TDR 的危险因素(比值比,8.32;95%置信区间 4.38-15.80 对于 CRF07_BC,P<0.05)。NNRTI 最常见的耐药 HIV-1 突变模式是 V106(1.31%,17/1297)和 E138(1.16%,15/1297),PI 是 M46(0.69%,9/1297)。共有 205 个(15.8%)pol 序列参与了遗传传播网络簇,CRF01_AE(比值比,2.369;95%置信区间 1.659-3.382;P<0.05)、B 亚型(比值比,13.723;95%置信区间 6.338-29.71;P<0.05)、耐药(比值比,0.306;95%置信区间 0.106-0.881;P<0.05)和不同教育水平(P<0.05)与聚类显著相关。
四川省 HIV-1 基因型分布更加多样化和复杂,男男性行为者(MSM)被低估,除了具有异性传播风险的老年人外,还需要在这一特定人群中扩大行为干预措施。新诊断患者 TDR 突变频率增加的风险凸显了对新治疗前 HIV-1 耐药性进行基因型耐药监测和分子监测的重要性。TDF、3TC 和 EFV 组成的方案仍然是目前首选的免费一线治疗方案。