中国 HIV 新发感染检测发展及未来 Development and Future of HIV-1 Incidence Assay in China Yan Jiang MD, PhD. National HIV Reference Laboratory, China CDC
中国 HIV 检测体系 HIV Testing in China Screening Confirmatory Recent Infection Treatment Drug Resistance EIA,RT WB,RIBA BED,Avidity CD4,Viral load in house, kits
BED 在中国的发展历程 Development of HIV Incidence Assay with BED in China 2005: BED assay was introduced into China 2006: Used to monitoring the HIV incidence at 1 province 2007: Extended to 7 provinces 2009: Extended to 16 provinces 2011: Extended to 31 provinces
China (May, 2008) All International Labs (May, 2008) Initial vs. Confirmatory Concordance 1.4 1.2 y = 1.0235x + 0.0016 R² = 0.9913 Confirmatory ODn 1.0 0.8 0.6 0.4 0.2 0.0 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 Initial ODn 全国 BED 检测实验室 PT 考核结果
HPTN 033 项目 BED 与队列研究发病率比较 BED-CEIA VS. Cohort Study(HPTN033) The HIV-1 Incidence of IDUs in Xinjiang Assay Total HIV + Recent Incidence (95%CI) BED 1170 225 34 8.2(5.5-11.0) Cohort 475 42 --- 8.8(6.3-12.0) Xiao Y, Jiang Y, Feng J, Xu W, Wang M, Funkhouser E, et al. Seroincidence of recent human immunodeficiency virus type 1 infections in China. Clin Vaccine Immunol 2007,14:1384-1386. The HIV-1 Incidence of IDUs in Guangxi Assay Total HIV + Recent Incidence (95%CI) BED 399 92 10 4.30(1.6-6.9) Cohort 500 15 --- 3.10(1.6-5.2) Wei L, Chen J, Rodolph M, Beauchamp G, Masse B, Li R, et al. HIV incidence, retention, and changes of high-risk behaviors among rural injection drug users in Guangxi, China. Subst Abus 2006,27:53-61.
2006-2007 云南省 FSW 人群 CIPRA 队列研究与 BED 方法新发感染率比较 The Comparison of Recent HIV Incidence from BED and Cohort Studies in Yunnan Province Supported by CIPRA, 2006-2007 Methods Survey at Baseline Survey Stage 6 months 12 months FSWs 737 747 705 FSWs in follow-up - 299 330 Seroconversion during follow-up - 2 2 Incidence from cohort studies/personyears (95% CI) - 1.3(0.2-4.7) 0.6(0.1-2.0) Long-term seroconversion(bed) 69 74 76 Recent seroconversion(bed) 7 15 16 Incidence from BED /personyears(95% CI) 0.7(0.1-1.2) 1.9 (0.7-3.1) 0.4(0.1-0.7) Xu J, Jiang Y, Wang N, et al. Drug use and sex work: competing risk factors for newly acquired HIV in Yunnan, ChinaPLoS One. 2013;8(3):e59050.
2002-2009 年云南省 IDU 人群 HIV 新发感染率 Recent HIV Incidence and Prevalence among IDU in Yunnan from 2002 to 2009 Prevalence Incidence Yang L, Ma YL, Luo HB,et al. A dynamic analysis on incidence and trend of HIV-1 epidemics among intravenous drug users, attendants at the STD clinics and pregnant women in Yunnan province, China. Zhonghua Liu Xing Bing Xue Za Zhi. 2008;29(12):1204-7.
2006-2009 重庆市 MSM 人群 HIV 新发感染率 Recent HIV incidence and prevalence among MSM in Chongqing from 2006 to 2009 Prevalence Incidence Han M, Feng LG, Jiang Y, et al. Surveillance on HIV-1 incidence among men who have sex with men in Chongqing, China, 2006-2008. Zhonghua Liu Xing Bing Xue Za Zhi. 2009 Sep;30(9):878-81.
2011-2012 年哨点监测重点人群新发感染检测结果
BED 方法在不同国家的误判率比较 BED False Recent Rate (FRR) for China IDU and Comparison to Other Countries
亲和力方法重复性和准确性验证试验 Verification the Repeatability and Accuracy of LAg in China Precision of 70 runs OD values ODn values mean SD CV% mean SD CV% NC 0.076 0.029 37.6 0.111 0.040 36.5 CAL 0.690 0.061 8.8 1.000 0.000 0.0 LPC 0.335 0.041 12.3 0.486 0.036 7.5 HPC 1.400 0.109 7.8 2.033 0.105 5.1
6.000 不同检测人员检测结果的一致性 Correlation of Different Technicians 5.000 ODn value of every person 实验员各自 O D n 值 4.000 3.000 2.000 1.000 0.000 0.000 1.000 2.000 3.000 4.000 5.000 6.000 四名实验员平均 ODn 值 Average ODn value of 4 person 实验员 a 实验员 b 实验员 c 实验员 d China CDC Average ODn value of 4 person A 实验室四人 ODn 值均值 6.000 5.000 4.000 3.000 2.000 1.000 0.000 y = 0.8877x + 0.1392 R 2 = 0.9849 0.000 1.000 2.000 3.000 4.000 5.000 6.000 7.000 US CDC ODn value 美国疾控中心实验室 ODn 值
亲和力方法的研究 Characterization of LAg in China Mean Duration of Recency China seroconversion specimens False Recent Ratio China specimens from individuals with true long-term infections (>1 year), ART-naïve Misclassification of specimens from ART patients
新发感染窗口期研究 : 阳转样本 Mean Duration of Recency Originally Tested Specimens: 94 Panels from Yunnan (n=304 samples) 91 Panels from Dehong (n=386 samples) Not all panels were useful for MDRI calculation due to missing information, ART use, poor Ab kinetics, single specimen per panel, etc. Specimens Used for MDRI Calculation: 25 Panels from Yunnan (n=119 samples) 11 Panels from Dehong (n=70 samples)
中国现场阳转盘 China SC Panels 5.0 LAg ODn 4.5 4.0 3.5 3.0 2.5 2.0 1.5 Using SACEMA s binomial regression method: MDRI = 121 days (95% CI 99-145 days) 1.0 0.5 0.0 0 200 400 600 800 1000 Estimated Days Since SC N= 35 Panels N=189 specimens
中国现场研究 : 误判率 China False Recent Rate (FRR) China Specimens for Analysis*: Yunnan: 257 Individuals Guizhou: 222 Individuals *Some specimens were excluded due to HIV neg, collection interval < 1year, etc. Each individual had 2 serial specimens collected. For Guizhou, the average time between specimens is 3.2 years. Data not available for Yunnan. FRR calculated using the ODn results from the follow-up specimen to ensure infection is >1 year.
感染一年以上样本的总体误判率 Overall FRR Origin Type # Specimens Subtype FRR 1.5 ODn LAg Long-term >1 year 479 C 2.30%* BED 6.6% *10/11 False Recents came from Guizhou while only 1/11 came from Yunnan.
Misclassification of ART patients Specimens from Individuals on ART No other clinical information (duration of infection, duration of ART, etc.) is available Tested both on BED and LAg N=726 Specimens
抗病毒治疗病人样本的误判率 Misclassification of ART Patients Sedia Avidity ODn 6.000 Sedia&BED(ART 726 specimens) 5.000 4.000 3.000 2.000 1.000 0.000 0.000 0.800 1.600 2.400 3.200 4.000 4.800 BED ODn
BED 与亲和力方法检测具有不同 CD4 细胞计数感染者和病人的结果 The Testing Results of AIDS Samples with Different CD4 Count Using LAg-Avidity EIA and BED-CEIA CD4 cell count (cell/ul) N BED-CEIA LAg-Avidity EIA RECENT FRR(%) RECENT FRR(%) <200 503 29 5.77 7 1.39 200~ 34 2 5.88 0 0.00 300~ 20 0 0.00 0 0.00 400~ 12 0 0.00 0 0.00 400 9 0 0.00 0 0.00 Unclear 13 1 7.69 0 0.00 Total 591 32 5.41 7 1.18
下一步工作 BED 与亲和力应用的比较研究培训质控技术推广与应用 Next step Comparing BED and LAg Training QA/QC Using for incidence assay
致谢国家参比室所有工作人员 GAP- 北京及美国实验室专家各省确证中心实验室 ACKNOWLEDGEMENTS All people from NARL team, GAP-China team, Province central laboratory teams