江苏省HIV-1长期不进展者人群特征分析-东南大学学报医学版

江苏省HIV-1长期不进展者人群特征分析

单位：1. 南京市第二医院科研科, 江苏南京 211100;
2. 江苏省疾病预防控制中心性病与艾滋病防制所, 江苏南京 210009

分类号：R512.91

出版年·卷·期（页码）：2026·45·第二期（193-203）

摘要：

目的:调查江苏省HIV-1长期不进展者(LTNP)流行病学特征。方法:基于中国艾滋病综合防治信息管理系统,纳入现住址为江苏省、确诊时基线CD4⁺T细胞计数≥500个·μL^-1、且感染时间≥1年的HIV-1感染者,构建回顾性队列。截至2023年12月31日末次随访,根据感染时间及历次CD4⁺T细胞计数动态,将研究对象分为LTNP和进展者(Progressor)。采用修正Poisson回归分析LTNP的影响因素;广义加性混合模型(GAMM)估算治疗前CD4⁺T细胞下降速率;广义估计方程(GEE)识别治疗前CD4⁺T细胞自然变化的相关因素。结果:截至2023年底,共筛选到符合入组条件的HIV-1感染者2 759例,其中LTNP 178例,Progressor 2 581例。178例LTNP中有105例在确诊7年之后接受了抗逆转录病毒治疗(ART),73例仍未接受治疗。多因素修正Poisson回归分析显示,确诊基线CD4⁺T细胞计数>600个·μL^-1(与确诊基线CD4⁺T细胞计数500~600个·μL^-1相比,aRR=2.911, 95%CI 2.098~4.040)、经异性性行为(与经同性性行为感染相比,aRR=1.641, 95%CI 1.123~2.397)、注射吸毒感染(与经同性性行为感染相比,aRR=2.791, 95%CI 1.591~4.899)、现住址地区为苏南(与现住址苏中相比,aRR=2.450, 95%CI 1.403~4.278)和苏北(与现住址苏中相比,aRR=2.328, 95%CI 1.303~4.159)与LTNP有关。GAMM和GEE模型均显示,治疗前LTNP组和Progressor组患者CD4⁺T细胞计数均呈现显著下降趋势,LTNP年均CD4⁺T细胞计数下降速率显著慢于Progressor(交互作用 P<0.05)。在平均确诊感染9.02年后,43.82%(78/178)的LTNP随访CD4⁺T细胞计数降低至500个·μL^-1以下。结论:江苏省LTNP 群体具有较高的基线CD4⁺T细胞计数,注射吸毒感染者的比例相对较高,多发现于苏南和苏北地区。LTNP群体CD4⁺T细胞计数呈现逐年衰减的趋势,提示对LTNP开展"早治疗"的抗病毒治疗策略同样意义重大。

Objective: To investigate the epidemiological characteristics of long-term non-progressors(LTNP) among HIV-1-infected individuals in Jiangsu Province, China. Methods: A retrospective cohort study was conducted using data from the National HIV/AIDS Comprehensive Response Information Management System of China. HIV-1-infected individuals residing in Jiangsu Province with a baseline CD4⁺ T cell count≥500 cells·μL^-1 at diagnosis and an estimated infection duration of at least one year were included. Participants were classified as LTNPs or progressors based on infection duration and longitudinal CD4⁺ T cell dynamics up to the last follow-up on December 31, 2023. Modified Poisson regression was used to identify factors associated with LTNP status. Generalized additive mixed models(GAMMs) were applied to estimate pre-treatment CD4⁺ T cell decline rates, and generalized estimating equations(GEEs) were used to identify factors associated with natural CD4⁺ T cell changes prior to antiretroviral therapy(ART). Results: A total of 2 759 HIV-1-infected individuals met the inclusion criteria, including 178 LTNP and 2 581 progressors. Among the 178 LTNP, 105 initiated ART more than seven years after diagnosis, while 73 remained ART-nave. Multivariable modified Poisson regression analysis showed that a baseline CD4⁺ T cell count >600 cells·μL^-1[compared with 500-600 cells·μL^-1, adjusted relative risk(aRR)=2.911, 95% confidence interval(CI) 2.098-4.040], heterosexual transmission(vs. homosexual transmission, aRR=1.641, 95% CI 1.123-2.397), injection drug use(vs. homosexual transmission, aRR=2.791, 95% CI 1.591-4.899), and residence in southern Jiangsu(vs. central Jiangsu, aRR=2.450, 95% CI 1.403-4.278) or northern Jiangsu(vs. central Jiangsu, aRR=2.328, 95% CI 1.30-4.159) were independently associated with LTNP status. Both GAMM and GEE analyses demonstrated significant declines in pre-treatment CD4⁺ T cell counts in both LTNP and progressors, with a significantly slower annual decline among LTNP(interaction P<0.05). After a mean infection duration of 9.02 years, 43.82%(78/178) of LTNP experienced a decline in CD4⁺ T cell counts to below 500 cells·μL^-1 during follow-up. Conclusion: LTNP in Jiangsu Province were characterized by higher baseline CD4⁺ T cell counts, a relatively higher proportion of individuals infected through injection drug use, and a higher prevalence in southern and northern Jiangsu. Despite slower CD4⁺ T cell decline, LTNP exhibited a progressive decrease in CD4⁺ T cell counts over time, highlighting the importance of early initiation of ART even in this population.

参考文献：

[1] GURDASANI D,ILES L,DILLON D G,et al.A systematic review of definitions of extreme phenotypes of HIV control and progression[J].AIDS,2014,28(2):149-162.
[2] 刘佳,樊盼英,薛秀娟,等.河南省HIV感染长期不进展者及病毒控制者病例特征分析[J].中华流行病学杂志,2016,37(2):227-231.
[3] 周信娟,朱秋映,李剑军,等.广西壮族自治区HIV感染长期不进展者特征及相关影响因素分析[J].中华流行病学杂志,2019,40(1):70-73.
[4] 郭敏,贾曼红,马艳玲,等.云南省HIV感染者病程长期不进展影响因素条件Logistic回归分析[J].中国皮肤性病学杂志,2015,29(9):927-929,983.
[5] HAN J,WU Z,MCGOOGAN J M,et al.Overrepresentation of injection drug use route of infection among human immunodeficiency virus long-term nonprogressors:a nationwide,retrospective cohort study in China,1989-2016[J].Open Forum Infect Dis,2019,6(5):ofz182.
[6] LI A H,WU Z Y,JIANG Z,et al.Duration of human immunodef iciency virus infection at diagnosis among new human immunodef iciency virus cases in Dehong,Yunnan,China,2008-2015[J].Chin Med J,2018,131(16):1936-1943.
[7] SHI L,TANG W,LIU X,et al.Trends of late HIV presentation and advance HIV disease among newly diagnosed HIV cases in Jiangsu,China:a serial cross-sectional study from 2008 to 2020[J].Front Public Health,2022,10:1054765.
[8] LANGFORD S E,ANANWORANICH J,COOPER D A.Predictors of disease progression in HIV infection:a review[J].AIDS Res Ther,2007,4:11.
[9] NAJAFI GHOBADI K,MAHJUB H,POOROLAJAL J,et al.Joint modeling of longitudinal outcome and competing risks:application to HIV/AIDS data[J].J Res Health Sci,2023,23(1):e00571.
[10] MADEC Y,BOUFASSA F,AVETTAND-FENOEL V,et al.Early control of HIV-1 infection in long-term nonprogressors followed since diagnosis in the ANRS SEROCO/HEMOCO cohort[J].J Acquir Immune Defic Syndr,2009,50(1):19-26.
[11] MANDALIA S,WESTROP S J,BECK E J,et al.Are long-term non-progressors very slow progressors? Insights from the Chelsea and Westminster HIV cohort,1988-2010[J].PLoS One,2012,7(2):e29844.
[12] CAPA L,AYALA-SUÁREZ R,DE LA TORRE TARAZONA H E,et al.Elite controllers long-term non progressors present improved survival and slower disease progression[J].Sci Rep,2022,12(1):16356.
[13] XU L,LIU Y,SONG X,et al.Nave CD4⁺ cell counts significantly decay and high HIV RNA levels contribute to immunological progression in long-term non-progressors infected with HIV by blood products:a cohort study[J].BMC Immunol,2021,22(1):36.
[14] VAN DER HELM J J,GESKUS R,LODI S,et al.Characterisation of long-term non-progression of HIV-1 infection after seroconversion:a cohort study[J].Lancet HIV,2014,1(1):e41-e48.
[15] BENITO J M,ORTIZ M C,LEÓN A,et al.Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers[J].BMC Med,2018,16(1):30.
[16] COLOMER-LLUCH M,KILPELAINEN A,PERNAS M,et al.Viral and cellular factors leading to the loss of CD4 homeostasis in HIV-1 viremic nonprogressors[J].J Virol,2022,96(1):e01499-e01421.
[17] CHEN L,YANG J,ZHANG R,et al.Rates and risk factors associated with the progression of HIV to AIDS among HIV patients from Zhejiang,China between 2008 and 2012[J].AIDS Res Ther,2015,12:32.
[18] YAN H,YANG H,LI J,et al.Emerging disparity in HIV/AIDS disease progression and mortality for men who have sex with men,Jiangsu Province,China[J].AIDS Behav,2014,18 Suppl 1(0 1):S5-S10.
[19] ZHANG J,HUANG X J,TANG W M,et al.Rapid clinical progression and its correlates among acute HIV infected men who have sex with men in China:findings from a 5-year multicenter prospective cohort study[J].Front Immunol,2021,12:712802.
[20] YIN Y,LIU Y,ZHU J,et al.The prevalence,temporal trends,and geographical distribution of HIV-1 subtypes among men who have sex with men in China:a systematic review and meta-analysis[J].Epidemiol Infect,2019,147:e83.
[21] JIANG Y,ZHANG L,HOU Z,et al.Prevalence of different genotypes of HIV-1 in injection drug users in China:a systematic review and meta-analysis[J].Curr HIV Res,2019,17(4):240-257.
[22] CUI H,GENG W,SUN H,et al.Rapid CD4⁺ T-cell decline is associated with coreceptor switch among MSM primarily infected with HIV-1 CRF01_AE in Northeast China[J].AIDS,2019,33(1):13-22.
[23] LI X,XUE Y,CHENG H,et al.HIV-1 genetic diversity and its impact on baseline CD4⁺T cells and viral loads among recently infected men who have sex with men in Shanghai,China[J].PLoS One,2015,10(6):e0129559.
[24] YE J,CHEN J,WANG J,et al.CRF07_BC is associated with slow HIV disease progression in Chinese patients[J].Sci Rep,2022,12(1):3773.
[25] BUCH S,PERIYASAMY P,THANGARAJ A,et al.Opioid-mediated HIV-1 immunopathogenesis[J].J Neuroimmune Pharmacol,2020,15(4):628-642.
[26] AZZONI L,METZGER D,MONTANER L J.Effect of opioid use on immune activation and HIV persistence on ART[J].J Neuroimmune Pharmacol,2020,15(4):643-657.
[27] MADHURAVASAL KRISHNAN J,KONG L,KARNS R,et al.The synthetic opioid fentanyl increases HIV replication and chemokine co-receptor expression in lymphocyte cell lines [J].Viruses,2023,15(4):1027.
[28] BUCH S,PERIYASAMY P,THANGARAJ A,et al.Opioid-mediated HIV-1 immunopathogenesis [J].J Neuroimmune Pharmacol,2020,15(4):628-642.
[29] AZZONI L,METZGER D,MONTANER L J.Effect of opioid use on immune activation and HIV persistence on ART [J].J Neuroimmune Pharmacol,2020,15(4):643-657.

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