海南省及云南西双版纳州HIV-1的分子流行病学比较研究

Comparison of Molecular Epidemiology on HIV-1 between Hainan Province and Xishuangbanna Dai Autonomous Prefecture of Yunnan Province

目的调查比较HIV-1在海南省及云南西双版纳州的流行情况及分子流行病学分析高危因素传播的情况以及传播链的鉴定。方法我们与海南省CDC及西双版纳州CDC合作在其境内开展了HIV血清学调查,筛查了海南省(1991～2006)及西双版纳州(1996～2005)高危人群志愿者血清样本。在本次两地调查中,我们通过系统进化分析方法,对已诊断的HIV感染者进行分子流行病学的追踪,来分析其中的主要流行亚群以及结合个案追踪进行传播链的鉴定。结果我们共筛查了海南省499725人,共检出HIV阳性感染者523例(0.1%),以注射器吸毒感染为主要传播途径(经共用注射器吸毒感染占69.2%、经性接触传播占19.3%、供血和使用血液/血液制品感染占3.3%、母婴传播占0.8%、不详占7.7%)。然而,在西双版纳州筛查中发现了较海南省高20倍的检出率:在25390受检人中,共检出HIV阳性感染者501例(2%)并以异性性传播为主(经异性性接触传播占77.3%、经共用注射器吸毒感染占21.1%、经同性性接触传播占0.4%、母婴传播占1.2%)。在海南省抽样的83人中,以CRF01--AE重组亚型(70人,84.3%)为主要病毒亚型,其他病毒亚型包括B’亚型(8人)、C亚型(2人)、CRF08-BC重组亚型(1人)、B亚型(1人)和1个未报道过的CRF01-AE/B’重组亚型。同样,在版纳抽样的44人中,也以CRF01-AE重组亚型(27人,61.3%)为主要病毒亚型,其他病毒亚型包括CRF08-BC重组亚型(15人)、G亚型(1人)、和1个未报道过的B/C重组亚型。在海南省抽样中有66人(79.5%)分布于4个大小不同的传播群,传播群1(59人)较大(奠基效应),属于CRF01-AE重组亚型,传播群2、3、4则较小,分别为3、2、2人,分别属于CRF01-AE重组亚型、C亚型和B’亚型。相反,在版纳抽样中有18人(40.9%)分布于8个较小的传播群(每群平均含2.25感染个体)。在海南省抽样中怀疑的6对异性性接触的传播链中,经系统进化分析方法确认了其中的4对,2对被拒绝。在版纳抽样中怀疑的8对异性性接触的传播链中,经系统进化分析方法确认了其中的5对,2对被拒绝,1对无法分析,此外还新发现了3对异性性接触传播群。结论HIV-1感染者的分子流行病学的追踪和分析对于追溯艾滋病流行的源头和地区性预防策略的制定有着重大的意义。

Objective To compare the prevalence of HIV and the molecular epidemiological linkages related to risk factors of viral transmission in the 2 major tourist regions of southern China： Hainan island and Xishuangbanna Dai Autonomous Prefecture of Yunnan province. Methods HIV serological study was conducted in individuals with potential high-risk behaviors between 1991 and 2006 in Hainan province and those between 1996 and 2005 in Xishuangbanna Dai Autonomous Prefecture （Banna） of Yunnan province under the guidelines of the governmental HIV/AIDS surveillance program. By phylogenetic reconstruction, we performed a molecular epidemiological tracing in representative subsets of the HIV-l-seropositive individuals diagnosed during these surveys. Results Of 499 752 individuals tested in Hainan, 523 （0.1% ） accumulated cases of HIV-1 infection were diagnosed with a dominant transmission by injecting drug users （IDUs） （69.2 % IDUs, 19.3 % heterosexually acquired adults, 3.3 % receivers of blood transfusion, 0.8% children born from HIV-1-infected mothers, and 7.7 % remained unknown）. Strikingly, a twenty-fold higher prevalence of HIV-1 was observed in Banna： of 25 390 individuals tested, 501 （2%） accumulated cases of HIV-1 infection were diagnosed with a dominant heterosexual transmission （77.3 % in heterosexual adults, 21.1% in needle-sharing drug users, 0.4% in homosexual adults, and 1.2% in children born from infected mothers）. Importantly, a dominant HIV-1 subtype CRF01-AE was identified in both geographic regions. Among 83 patients samples examined in Hainan （70 were infected with HIV-1 subtypes CRF01-AE and 8, 2, 1, 1, and 1 were B＇, C, CRF08-BC, B, and a new CRF01-AE/B＇ recombinant, respectively）, 66 （79.5%） were segregated into 1 large cluster （59 sequences） （founder effect） and 1 small cluster （3 sequences） of CRFO1-AE, 1 small cluster （2 sequences） of B＇ and 1 small cluster （2 sequences） of C. In contrast, among 44 heterosexually infected and antiretroviral-naive individuals examined in Banna （27 infected with HIV- 1 subtype CRF01-AE, 15 with CRF08-BC, 1 with G, and 1 with a new B/C recombinant）, 18 （40.9%） were coclustered into 8 transmission chains with an average size of 2.25 infections per chain. Phylogenetic and epidemiological linkages confirmed 4 heterosexual transmission events and rejected 2 potential heterosexual transmission suggested by contact tracing in Hainan and confirmed eight heterosexual transmission events in Banna. Conclusions The reconstruction of current HIV-1 outbreaks by molecular epidemiological tracing is helpful for identifying epidemic sources and for defining prevention strategies in different geographic regions.