CCR5基因启动子59029位点单核苷酸多态性与HIV-1疾病进展关系的Meta分析

目的探讨CCR5基因启动子59029位点单核苷酸多态性(SNPs)与HIV-1感染者疾病进展的关系。方法按照制定的检索策略,在PubMed、CBM、VIP等数据库检索有关CCR5基因启动子59029位点SNPs与HIV-1感染者疾病进展关系的研究,按照纳入和排除标准选取文献,评价文献质量,提取相关数据。用Stata 10.0统计软件对数据进行Meta分析。结果按照纳入和排除标准,共纳入4个病例对照研究,其中长期不进展者(LTNP)总例数375人,快速进展者(RP)总例数282人。Meta分析结果显示,在排除了CCR5Δ32和CCR2-64I突变后,RP组的59029A/A纯合子基因型频率是0.235,高于LTNP组的0.144,两者差异具有统计学意义(Z=2.37,P=0.018),OR及95%CI是3.441(1.236,9.582)。RP组的59029A等位频率是0.513,也高于LTNP组的0.370(Z=3.13,P=0.002)。结论 CCR5基因启动子59029A等位与HIV-1疾病的快速进展相关。     

长期不进展者与艾滋病患者HIV-1 nef特异性CD8+ T细胞应答的初步研究

目的　探讨我国HIV 1nef特异性CD8 T细胞应答的特点及其免疫保护作用。方法以长期不进展组 (LTNP) 7例和艾滋病组 9例为研究对象 ,以覆盖HIV 1nef全长的 2 6个重叠肽段组成的 3个肽段库作为刺激原 ,用IFN ELISPOT方法检测LTNP组与艾滋病组患者HIV 1nef特异性CD8 T细胞应答 ,并测定其CD4 T细胞、CD8 T细胞和病毒载量 ,观察两组间HIV 1nef特异性CD8 T细胞应答的差异及其与CD4 T细胞和病毒载量的相关性。结果　LTNP组和艾滋病组HIV 1nef特异性CD8 T细胞应答的强度分别为 4 0 4± 334和 5 9± 12 1SFC/ 10 6外周血单个核细胞 (PBMC) ,LTNP组显著高于艾滋病组 ;HIV 1nef特异性CD8 T细胞应答的强度与CD4 T细胞计数呈正相关 ,但与病毒载量没有显著的相关性。结论　HIV 1nef特异性CD8 T细胞应答在艾滋病发病中具有一定的保护作用 ,欧美流行株与我国流行株之间具有免疫交叉反应性     

Association between Nef-specific CD8 T-cell responses and disease progression in HIV-1 subtype B infection

Background The correlation between HIV-1 Nef-specific CD8 T-cell responses and markers of HIV-1 disease progression still remains unclear. This study analysed and compared the role of HIV-1 Nef-specific CD8 T-cell responses in patients with different disease status. Methods Two groups of patients with HIV-1 subtype B infection were selected according to CD4 count and clinical manifestations： long-term nonprogresssors （LTNPs, n = 20） and advanced progressors （APs, CD4 count 〈500 cells/pl, n = 34）. Nef-specific CD8 T-cell responses were studied by interferon- T ELISpot assay against 3 pools of HIV-Nef peptides. Results Nef-specific CD8 T-cell responses did not correlate with viral load or CD4 count in all patients and no significant differences were found in the magnitude of Nef-specific CD8 T-cell responses between groups LTNPs and APs （670 SFC/106 peripheral blood mononuclear cells vs 1107 SFC/106 peripheral blood mononuclear cells, P = 0.255）. Further comparisons showed that there were also no significant correlations observed in group LTNPs, but Nef-specific CD8 T cells correlated negatively with viral load （r = -0.397, P = 0.020） and positively with CD4 count （r = 0.364, P = 0.034） in group APs. Conclusion These data suggest that different correlation patterns between Nef-specific CD8 T-cell responses and disease progression exist in LTNPs and APs. Although a negative association was observed with concurrent plasma HIV RNA in APs, Nef-specific CD8 T-cell responses might fail to play a protective role in different stages of HIV- 1 infection.     

中国人群HLA-B基因多态性与HIV关联性的Meta分析

目的：系统评价中国人群HLA-B 基因多态性与HIV 易感性及疾病进程的关系。方法全面检索查找已发表的相关病例对照研究及横断面研究，并追溯其参考文献，按纳入和排除标准进行文献筛选、资料提取及质量评价，使用RevMan 4．2及SAS 9．1．3软件进行统计分析。结果共纳入11篇文献。6篇为HLA-B基因与HIV疾病进程相关性研究，Meta 分析结果显示，HLA-B＊27、HLA-B＊51和HLA-B＊58为HIV/AIDS 病程进展的保护性基因，合并比值比分别为0．49、0．61和0．65。 HLA-B＊35为HIV/AIDS 病程进展的危险基因，合并比值比为1．87。5篇为HLA-B基因与HIV易感性的关联性研究，Meta分析结果显示，HLA-B＊37和HLA-B＊46为HIV感染的易感性基因，合并比值比分别为1．62和1．19。 HLA-B＊39为 HIV 感染保护性基因，合并比值比为0．67。结论 HLA-B＊27、HLA-B＊51和HLA-B＊58可能延缓而 HLA-B＊35可能加速中国人群 HIV 感染后的疾病进程；HLA-B＊39可能降低而HLA-B＊37和HLA-B＊46可能增高中国人群对HIV感染的易感性。     

HIV-specific T cell immunity across the entire HIV genome in Chinese men who have sex with men

Background Man who has sex with man （MSM） is one of the high risk groups for spreading HIV/AIDS. It was reported that the most prevalent human irnmunodeficiency virus type 1 （HIV-1） strain among MSM is subtype B; however, T cell immunity remains unknown across the HIV-1 B genome in this population. Methods Using Elispot assay with synthetic peptides spanning the sequence of HIV-1 consensus B, HIV-l-specific cytotoxic T-cell lymphocyte responses were quantified among 3 treated and 19 untreated HIV-1 infected MSM from Beijing, China. Cross-sectional association between viral loads and cellular immune responses were analyzed. Results Peptide pools corresponding to each HIV-1 protein were used for Env, Gag, Pol, Nef, Tat/Rev, Vpr/Vpu and Vif. The results showed that the magnitude of T cell responses in the 3 treated HIV^＋ MSM group [median, 770 spot forming cells （SFCs） per 106 peripheral blood mononuclear cells （PBMCs）] might be significantly lower than that in the 19 untreated HIV^＋ MSM group （median, 6175 SFCs per 106 PBMCs）. Nef, Gag and Pol are the most frequently targeted HIV-1 antigens; and 16 subjects （73%） were identified with vigorous T cell immunity against each of these three proteins. The overall magnitude of T cell immunity closely related to its breadth （r=-0.72, P〈0.05） and was inversely but weakly associated with viral loads （r=-0.15）. Further analysis showed that both Gag （r=-0.24） and Pol specific T cells （r=-0.12） contributed to this inverse association whereas Nef specific T cells showed no association with viral loads. Conclusions The magnitude of HIV-1 specific T cells is inversely but weakly associated with viral loads among MSM; HIV-specific T cell responses against conservative sequences （Gag and Pol） are the main contributors to this association among Chinese HIV^＋ MSM. These findings have important implications for vaccine design.     

Complete Human Immunodeficiency Virus-1 Specific T Lymphocyte Response to Chinese Human Immunodeficiency Virus-1 B/C Chronic Infectors

Objective To characterize the human immunodeficiency virus （HIV） -specific T lymphocyte responses and identify the immunodominant regions in Chinese HIV-1 recombinant subtype B/C chronic infectors at complete genome level. Methods Twenty-five HIV-I B/C recombinant chronic infectors were screened for their specific T lymphocyte responses to a panel of peptides corresponding to the complete HIV-1 subtype B genome by gamma interferon ELISPOT assay. Kruskal-Wallis nonparametric analysis of variance was used to test significant differences across gene regions, and Tukey pairwise analysis was used to identify differences between gene regions. Spearman rank correlation was used to assess the relation between responses. Results The order of recognized frequencies of specific T lymphocyte responses to HIV proteins was Nef〉Vpr〉Gag〉Pol〉Vpu〉Env〉Rev〉Vif〉Tat. When adjusted for protein length, Nef, Vpr, Gag, and Pol were the most intensely targeted proteins and the central region of Nef, Gag p24, Pol RT, and Vpr was most frequently recognized. No significant correlation was observed between the magnitude of IFN-γ production of HIV-l-specific T lymphocyte responses and plasma viremia, breadth of response and CD4 counts. Conclusion The central region of Nef, Gag p24, Pol RT, and Vpr is most frequently targeted in HIV-1 B/C recombinants chronic infectors. HIV-1-specific T lymphocyte responses and plasma viremia or CD4 counts play no protective role at complete genome level in these infectors.     

中国HIV-1感染者病毒特异性细胞毒性T细胞定量研究

目的对8例HIV长期感染不进展(LTNP)及病程进展缓慢(SP)患者的病毒特异性细胞毒性T细胞(CTL)特征进行研究。方法设立队列研究,从中随机选出8例患者(4例LTNPs,4例SP)。通过采用重叠肽技术组建HIV-1B亚型全序列肽段,组建成三维肽库进行ELISPOT分析8例患者的HIV-1特异性细胞免疫反应。结果在大多数患者中存在较强的T细胞反应,特别对HIV-1病毒的pol、gag、nef蛋白的免疫反应比其他蛋白强。结论病毒特异性CTL免疫反应在HIV-1 LTNPs有较强并且很广泛的反应,这对于有效抑制病毒在人体内的生存有可能起到很大的作用,很可能是这些LTNPs及SP病程进展缓慢的主要原因之一。     

中国部分地区HIV感染者/艾滋病患者外周血单核/巨噬细胞功能与疾病的进展关系

目的 通过对中国HIV感染者／艾滋病（AIDS）患者外周血单核／巨噬细胞标志抗原CD14及其早期活化分子CD69的研究,探讨其外周血单核／巨噬细胞的功能状态与HIV感染者疾病进程的关系。方法采集57例未经抗病毒治疗的HIV感染者／AIDS患者及32例健康人抗凝全血,运用流式细胞分析技术对CD4^＋T淋巴细胞、CD14^＋细胞及其CD69抗原表达情况进行测定,并采用实时荧光定量RT-PCR技术检测患者血浆HIV-1载量。结果（1）HIV感染者／AIDS患者外周血CD14^＋细胞颗粒度SSC值为76±16,CD69分子在CD14^＋细胞的表达率为27％±4％,均明显高于对照组（P〈0．05）,其中AIDS组高于HIV慢性感染（HIV）组及长期不进展（LTNP）组,HIV组高于LTNP组（P〈0．05）,LTNP组与对照组比较差异无统计学意义;外周血CD14^＋细胞比例、CD14抗原水平与对照组相比差异无统计学意义。（2）HIV感染者／AIDS患者外周血CD69分子在CD14^＋细胞的表达率与CD4^＋T淋巴细胞绝对值呈明显负相关（r=-0．872,P〈0．01）,与HIV-1RNA病毒载量呈显著正相关（r=0．697,P〈0．01）。结论中国部分地区HIV／AIDS患者外周血单核／巨噬细胞的活化和吞噬功能较健康对照组有显著上升,且与疾病进展密切相关。     

桂林市经性传播的HIV-1的流行特征和亚型分析

目的：了解桂林市2008年及以后确诊的经性传播的人类免疫缺陷病毒1型( HIV-1)感染者的流行病学及亚型的分布情况。方法选取样本100例,收集流行病学资料,采集抗凝全血,提取病毒RNA,RT-PCR法行gag基因扩增,对产物进行测序和分析。结果100例样本中男女比例为2．125∶1;青壮年年龄组(20~49岁)患者为54%,>50岁年龄组患者为45%;职业为农民的患者为40%,学生为6%;初中及以下文化水平患者占69%;经异性和同性性接触途径传播的分别为93%、7%。100例样本最终成功扩增得到61例样本的 gag 基因序列, CRF01-AE 重组亚型48例, CRF07-BC重组亚型8例,B亚型5例。结论应更加重视婚检、孕检的艾滋病抗体筛查;关注老年人群经性接触途径感染艾滋病的现象;采取针对低素质人群的有效防治措施;随着主要传播途径和主要亚型的变化,迫切需要对高危人群进行宣传教育和行为干预以阻断HIV/AIDS的流行和传播。     

抗HIV-1 gp120单克隆抗体体外阻断CD4细胞HIV感染的研究

目的:抗HIV-1gp120单克隆抗体对细胞感染HIV的拮抗作用研究。方法:制备抗HIV-1gp120单克隆抗体,鉴定其特性;研究抗HIV-1gp120单克隆抗体对细胞感染HIV的拮抗作用。结果:构建的重组质粒的外源基因片段经测序与预期HIV-1gp120抗原基因片段大小一致;高浓度时该单克隆抗体能够抑制HIV病毒的感染,随着抗体浓度的降低,中和实验的抑制率也随之下降;高浓度时该单克隆抗体能够显著抑制病毒的感染,随着抗体浓度的降低,HIVgp120RNA定量增高。结论:获得6株稳定分泌抗HIV-1gp120单克隆抗体的杂交瘤细胞株,该抗HIV-1gp120单克隆抗体具有一定的抗HIV作用。     

HIV/AIDS患者KIR3DS1基因与部分环境因素对其疾病进展的影响

目的:探讨KIR3DS1基因及部分环境因素与人类免疫缺陷病毒(human immunodeficiency virus,HIV)-1感染者疾病进程的关系?方法:收集86例通过自愿咨询检测确认为HIV+患者的抗凝全血标本,采用聚合酶链反应-限制性片段长度多态性方法,检测其KIR3DS1基因,并进行问卷调查(调查内容包括人口学基本信息?临床表现?高危行为?是否接受抗病毒治疗等)收集部分环境因素信息?结果:Cox回归分析显示,风险比(RR)值为0.217(95%CI:0.098~0.480)?结论:抗病毒治疗可以延缓HIV-1感染者疾病进程,携带KIR3DS1基因可能延缓HIV-1感染者疾病进程?     

A serosurvey of hepatitis B virus,hepatitis C virus,human T lymphotropic virus type-1 and syphilis in HIV-1-infected patients in Jamaica

The seroprevalences of hepatitis B virus (HBV), hepatitis C virus (HCV), human T lymphotropic virus type-1 (HTLV-1) and syphyilis were determined in 129 HIV-1-infected patients using commercially prepared reagents. The seroprevalences were HCV, 0% (0/129); HBV, 37% (48/129); HTLV-1, 5% (6/129) and syphilis, 20% (26/129). Fifteen per cent (19/129) of the patients had active/chronic HBV infection. The seroprevalence of HBV was statistically significantly higher in HIV-1 infected men (24/49, 50% versus 17/80, 21%; p = 0.005), while the seroprevalence of syphilis was statistically significantly increased in HIV-1 infected patients in the over-40 age group (10/31, 32% versus 6/53, 11%; p = 0.05). These findings throw the spotlight on HBV infection and syphilis and suggest that these two sexually transmitted infections should be carefully surveyed in patients with HIV/AIDS in Jamaica. It is essential for management protocols in Jamaica to include screening for evidence of these co-infections.     

HLA-DR expression on regulatory T cells is closely associated with the global immune activation in HIV-1 infected subjects na(i)ve to antiretroviral therapy

Background The frequencies of regulatory T cells (Tregs) increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect and thereby account for the over-activation of Tregs during HIV infection. However, it remains unknown whether Tregs are also over-activated and thereafter the activation induced death may lead to the decrease of Tregs. Methods Tregs were defined as CD4+CD25+CD127lo/-T cells. Eighty-one HIV-1 infected patients were enrolled in our study, and twenty-two HIV-1 seronegative donors were recruited as the control. The levels of HLA-DR on Tregs were determined by FACSAria flow cytometer. ResultsCompared to HIV-1 seronegative donors, the levels of HLA-DR on CD4+CD25+CD127lo/- Tregs were significantly increased in HIV-1 infected patients, and its increase was positively associated with viral loads (r=0.3163,P=0.004) and negatively with CD4 T-cell counts (r=-0.4153, P<0.0001). In addition, significant associations between HLA-DR expression on CD4+CD25+CD127lo/-Tregs and the percentages of HLA-DR, CD38, Ki67 expressing CD4+ and CD8+ T cells were also identified. Conclusion HLA-DR on Tregs is a good marker for viral replication and disease progression. The over-activation of Tregs might result in the decrease of Tregs.     

ART治疗对HIV感染者CD4+FoxP3+T细胞水平的影响

目的:探索抗逆转录病毒疗法(ART)治疗在HIV-1疾病进程中对调节性T细胞(Treg细胞)的影响,并探讨Treg细胞频率在HIV-1疾病进程中的作用.方法:抽取114例(男96例、女18例)HIV-1阳性患者及17例健康对照者外周血,应用流式细胞术检测Treg细胞,并分析其表达水平(频率和绝对数)在 HIV-1疾病进程中的变化趋势及其与CD4+细胞绝对数之间的相关性.结果:随着HIV-1感染者病情进展,患者外周血中Treg细胞绝对数趋向下降并且与CD4+T细胞绝对数呈正相关,而Treg细胞频率趋向升高并且与CD4+T细胞绝对数呈负相关.Treg细胞频率及绝对数在ART治疗无症状HIV-1阳性感染者中显著降低,而在AIDS患者中却显著升高.结论:Treg细胞参与艾滋病免疫发病过程,并且在HIV-1感染的不同阶段,ART治疗对Treg细胞水平具有一定的影响,提示通过控制Treg细胞的水平可能有助于HIV-1感染疾病的临床控制.     

Association of IL-7 with disease progression in Chinese HIV-1 seropositive individuals

Background Elevated levels of interleukin-7 (IL-7) have been correlated with CD4(+) T cell depletion and the emergence of syncytium-inducing (SI) variants in human immunodeficiency virus type-1 (HIV-1) infection, and suggested as an indicator of acquired immunodeficiency syndrome (AIDS) disease progression. Therefore, we investigated the effects of IL-7 on disease progression and virus phenotype in Chinese HIV/AIDS patients. Methods In a cross-sectional study of 71 untreated HIV-1 seropositive individuals and 12 healthy donors, plasma IL-7 levels were determined by an ultra sensitive enzyme-linked immunosorbent assay (ELISA), and its relations to CD4(+) T cells, CD8(+) T cells, plasma viral loads and HIV phenotypes were analyzed. Results Significant higher IL-7 levels were found in Chinese HIV/AIDS patients [(3.33 ± 3.60) pg/ml] than those of health controls [(1.2 ± 0.81) pg/ml] ( P &lt;0.05), and IL-7 levels were inversely associated with CD4(+) T cell counts ( r = － 0.497, P &lt;0.01). Furthermore, IL-7 levels were significant higher in patients with SI variants [(9.12 ± 4.55) pg/ml] than those with non-syncytium-inducing variants [(1.50 ± 2.69) pg/ml] ( P &lt;0.01). Conclusions Increased IL-7 levels were found in Chinese HIV/AIDS patients and significantly associated with disease progression, thus increased IL-7 plasma levels may indicate disease progression.     

Toll样受体与HIV-1病毒感染

感染人类免疫缺陷病毒(HIV)后,引起免疫系统的持续激活,进而导致CD4+T细胞数目不断减少,最终导致人类免疫缺陷综合征(AIDS)的发生。阻断免疫系统的持续激活,可能是减缓AIDS发展进程的重要途径。有研究表明,Toll样受体(TLR)与HIV感染后免疫系统的持续激活密切相关。同时,TLR是重要的模式识别受体,在抗微生物的非特异性免疫中发挥重要作用并参与调节特异性免疫。本文综述了TLR与HIV-1的关系,以给HIV-1治疗及疫苗的研究提供参考。     

Evaluation of HIV-1 immunogen, an immunologic modifier, administered to patients infected with HIV having 300 to 549 x 10(6)/L CD4 cell counts: A randomized controlled trial

CONTEXT: Despite enormous improvements achieved through the use of antiretroviral therapies (ARTs), the risk for eventual human immunodeficiency virus (HIV) disease progression remains high. Agents that enhance the immunologic mechanism for viral recognition might reduce disease progression. OBJECTIVE: To determine whether the addition of HIV-1 Immunogen would confer added clinical efficacy to that achievable by ARTs. DESIGN AND SETTING: Multicenter, double-blind, placebo-controlled, randomized trial beginning March 1996 and ending May 1999 conducted at 77 centers in the United States providing primary care or referral care for persons infected with HIV. PATIENTS: Adults infected with HIV who have baseline CD4 cell counts between 300 x 10(6)/L and 549 x 10(6)/L without prior acquired immunodeficiency syndrome-defining conditions receiving stable ART (or no therapy) were screened and 2527 were randomized. INTERVENTIONS: Ten units of HIV-1 Immunogen, derived from a Zairian HIV isolate, inactivated and formulated with incomplete Freund adjuvant, was administered intramuscularly every 12 weeks. The placebo was incomplete Freund adjuvant. Changes in ARTs were allowed. MAIN OUTCOME MEASURES: HIV progression-free survival; secondary end points included overall survival, changes in HIV RNA, CD4 cell counts, CD4 percentage, body weight, and immunogenicity. RESULTS: The overall event rate was 1.8 per 100 person-years of follow-up. Fifty-three subjects developed clinical progression in each treatment group (relative risk [RR], 0.97; 95% confidence interval [CI], 0.66-1.42; P =.89). There were 19 and 23 deaths in the placebo and HIV-1 Immunogen groups, respectively (RR, 0.81; 95% CI, 0.44-1. 48; P =.49). There were no statistically significant differences between the groups with respect to changes in HIV RNA (P =.59), CD4 percentage (P =.63), or body weight (P =.89). Subjects in the HIV-1 Immunogen group had an increase in average CD4 cell count of approximately 10 x 10(6)/L greater than the placebo group (P =.02). CONCLUSION: HIV-1 Immunogen with unrestricted ART failed to demonstrate an increase in HIV progression-free survival. JAMA. 2000;284:2193-2202.     

Association of HLA-B Alleles With Human Immunodeficiency Virus Type 1 Infection in the Yi Ethnic Group in Sichuan Province

Objective To determine the distribution of HLA-B alleles in the Chinese Yi ethnic group and its association with HIV infection. Methods One hundred and six unrelated healthy HIV negative and 73 HIV positive Chinese Yi ethnic individuals were typed by PCR-SSP. Results The frequency of alleles B*07, B‘35, and B‘46 were increased in HIV-l-positive subjects, whereas the alleles B‘55, B‘44 and B‘78 were absent in the HIV-infected persons studied. The B‘46 allele was present in a significantly higher gene frequency among H/V-1-positive individuals (P--0.02, OR=3.32,95% CI=1.13-9.78) compared with control subjects. Conclusion HLA-B*46 may be associated with its susceptibility to H1V-1 infections.     

Immune activation markers in individuals with HIV-1 disease and their correlation with HIV-1 RNA levels in individuals on antiretroviral therapy

BackgroundCurrently CD4+ T lymphocyte counts and HIV-1 RNA levels are being utilized to predict outcome of human immunodeficiency virus (HIV) disease. Recently, the role of immune activation in HIV disease progression and response to treatment is being investigated. This study focused on the expression of CD38 and HLA-DR on lymphocyte subsets in various groups of HIV-infected individuals and to determine their association with HIV-1 disease progression.MethodsNinety-eight cases of patients with HIV/AIDS in different disease stages and twenty-four healthy HIV-negative individuals were included in the cross-sectional study. Their immune function and abnormal immune activation markers (CD38 & HLA-DR) were detected using a flowcytometer, and HIV-1 RNA levels in individuals receiving antiretroviral drugs were estimated.ResultsThe immune activation marker levels were significantly different between patients with different disease stages (P < 0.001). A significant negative correlation was observed between peripheral blood CD4+ T cell counts and immune activation markers. Also, a significant positive correlation was observed between HIV-1 RNA levels and CD38+CD8+ T lymphocyte.ConclusionImmune activation markers (CD38 & HLA-DR) increase with disease progression. CD38+ on CD8+ T lymphocyte correlates well with HIV1 RNA levels in individuals failing on antiretroviral therapy.