中国人类免疫缺陷病毒-1感染者细胞毒性T淋巴细胞特异性应答

目的 探讨中国人类免疫缺陷病毒（HIV）／艾滋病（AIDS）患者HIV特异性细胞毒性T淋巴细胞（CTL）应答的特征。方法 以HIV-1 B、C亚型构建的2个全基因组肽库作为抗原，通过酶联免疫斑点（ELISPOT）法检测HIV／AIDS患者HIV特异性CTL应答。结果 无论HIV-1 B亚型还是HIV-1 C亚型所构建肽库的应答效应和频率主要集中在Gag和Nef蛋白，其他蛋白也有不同程度的应答。HIV-1 B、C亚型间应答比较，整体范围大致相同，但单个肽段水平还存在着一定差异，B亚型应答频率最高的是Nef的GPKEPFRDYVDRFYKTLR（5／17，29．4％）和Gag的LWVYHTQGYFPDWQNY（5/17，29．4％），C亚型应答频率最高的是Gag的GPKEPFRDYVDRFFKTLR应答频率为35．29％。结论 中国人群CTL应答多集中在Gag和Nef蛋白，B、C亚型在单个肽段水平略有差异。提示中国人群的CTL应答研究对设计针对中国人群的HIV疫苗有较重要的意义。     

人类免疫缺陷病毒和丙型肝炎病毒重叠感染者的临床及免疫特征

目的 观察人类免疫缺陷病毒(HIV)和HCV重叠感染者与慢性丙型肝炎患者临床特征及HCV特异性细胞毒性T淋巴细胞(CTL)的数量及功能,探讨两组患者免疫功能的差异及其可能的影响因素.方法 以HIV和HCV重叠感染患者59例、慢性丙型肝炎患者36例为研究对象,取治疗前外周血检测肝脏生物化学指标、血常规、外周血T淋巴细胞亚群(CD4+T、CD8+T淋巴细胞计数)及HIV、HCV病毒载量,以酶联免疫斑点法检测HCV特异性CTL的数量和功能,统计学分析两组问免疫功能的差异及与上述检测指标的相关性. 结果 中国河南省有偿献血、单采血浆人群HIV感染者中HIV和HCV重叠感染率达60.8%.ALT、AST值在重叠感染组与HCV组间差异无统计学意义;球蛋白在重叠感染组为(40.3±5.8)g/L,HCV组为(32.8±6.3)g/L,差异有统计学意义(P＜0.01).重叠感染组外周血CD4+T淋巴细胞数明显低于HCV组(P＜0.01),而CD8+T淋巴细胞数高于HCV组(P＜0.01).重叠感染组HCV RNA定量高于HCV组(P＜0.01).重叠感染组对HCV-NS3区肽段的反应强度(每106个外周血单个核淋巴细胞中斑点形成细胞的个数)较HCV组弱,649.34±685.90对比1233.70±1085.16,差异有统计学意义(P＜0.05).重叠感染组白蛋白与HCV病毒载量呈现负相关(r=0.540);重叠感染组对HCV-NS3区肽段反应强度与HIV病毒载量负相关(r=0.356);重叠感染患者CD4+T淋巴细胞数与血小板正相关(P＜0.05).但未见重叠感染组HCV RNA与CD4+T淋巴细胞数量及HIVRNA水平有相关关系.结论 重叠HIV感染有利于HCV的复制,而HIV载量可影响针对HCV的特异性免疫反应,HIV载量高则不利于HCV的清除.慢性丙型肝炎患者重叠HIV感染时,病情易慢性化,预后更差.     

中国人类免疫缺陷病毒-1B亚型Gag蛋白特异性T淋巴细胞的免疫应答

大量研究证明,细胞免疫特别是HIV特异性CTL在控制HIV感染中发挥关键作用[1]。HIV-1特异性CTL应答不仅由HIV-1特异性抗原蛋白结构决定,同时也受到特异性人类白细胞抗原(HLA)I类抗原的限制。不同人群HLA-I类基因型分布频率不同,决定了不同人群HIV-1特异性CTL应答模式的不同[2]。目前HIV-1特异性CTL应答研究主要集中在白种人和黑种人,有关中国人HIV-1特异性CTL应答的研究不多,结论也不一致[3-4]。因此,本实验选用既往研究证明应答频率较高的结构蛋白Gag为靶蛋白,进一步明确中国人HIV-1特异性T淋巴细胞应答特点及HIV-1特异性T淋巴细胞反应与临床疾病进展的相关性。     

人类免疫缺陷病毒与重叠丙型肝炎病毒感染者免疫指标比较

目的 分析HIV/HCV重叠感染人群与HIV单独感染人群治疗前临床特征及免疫功能的差异,探讨其可能的影响因素.方法 以HIV/HCV重叠感染患者59例、HIV单独感染患者38例为研究对象,取患者治疗前外周血,检测其肝功能、血常规、外周血T细胞亚群(CD4+、CD8+)及HIV、HCV病毒载量,酶联免疫斑点法(ELISPOT)检测HIV特异性细胞毒性T淋巴细胞(CTL)的数量和功能.结果 HIV/HCV重叠感染率达60.8%.重叠感染组ALT、AST均明显高于HIV组(49.8 U/L比23.6 U/L,49.1 U/L比32.3 U/L,P值分别为0.000、0.013);重叠感染组PLT明显低于HIV组[(167.3±59.2)×109/L比(198.0±63.9)×109/L,P=0.040].外周血T细胞亚群检测结果两组间差异无统计学意义.重叠感染组HIV RNA定量为(4.046±0.541)lOglo拷贝/mL,低于HIV组的(4.394±0.507)log10拷贝/mL(P=0.018).重叠感染组对HIV-Gag全序列肽段的阳性孔斑点数(平均秩次30.85)较HIV组(平均秩次44.34)低,阳性孔数(4.60±5.52)低于HIV组(6.24±6.93),但两组比较差异无统计学意义.重叠感染组Alb与HCV病毒载量呈负相关(r=-0.540),CD4+与PLT呈正相关(P=0.000).结论 单采血浆感染HIV患者中,有较高的HIV/HCV重叠感染率和较低的细胞免疫功能.     

艾滋病合并丙型肝炎病毒感染者抗反转录病毒治疗效果和肝脏损伤

目的 评价对AIDS合并HCV感染患者抗反转录病毒治疗(ART)的临床疗效和肝损伤.方法 将患者按有无HCV合并感染分为HIV和HCV合并感染组(HIV/HCV组)65例,HIV感染组(HIV组)52例,应用两个核苷类反转录酶抑制剂(NRTI)联合一个非核苷类反转录酶抑制剂(NNRTI)的ART方案,疗程1年.随访并检测血浆HIV载量、外周血CD4细胞数、ALT.结果 治疗前,HIV/HCV组和HIV组的HIV载量均值分别为5.59和5.89 log10拷贝/mL,治疗1年后,分别降至2.91 log10拷贝/mL(P＜0.05)和2.88 log10拷贝/mL(P＜0.05),两组分别有83.1%和78.9%的患者HIV载量＜500拷贝/mL.HIV/HCV组和HIV组CD4细胞均值由治疗前的73.9和72.4/μL,分别增至215.1/μL和214.8/μL(P值均＜ 0.05).1年内,HIV/HCV组与HIV组肝功能异常率分别为24.6%与7.7%(P＜0.05),但无因发生严重肝损伤而终止ART者.结论 联合应用NRTI、NNRTI治疗AIDS合并HCV感染患者,短期内能有效抑制HIV复制,促进免疫功能重建.HCV感染虽可加重肝损伤,但对ART疗效无明显影响.     

HIV感染长期不进展者与艾滋病患者HIV-1 gag特异CD_8~ T细胞应答

目的　探讨欧美流行的人类免疫缺陷病毒 (HIV) 1B亚型株与我国HIV感染和艾滋病 (AIDS)病人 gag特异性CD 8T细胞应答交叉反应性。方法　研究对象为长期不进展者 (LTNP) 7例和艾滋病患者 9例 ,将覆盖HXB2HIV 1gag全长的 12 5个重叠肽段组成 11个肽段库作为抗原 ,用γ干扰素刺激原酶联免疫斑点试验方法检测LTNP和AIDS病人的特异性CD 8T细胞应答 ,观察两组病人间的差异及其与CD 4 T细胞和病毒载量的相关性。结果　LTNP组和AIDS组HIV 1gag特异性CD 8T细胞应答强度分别为 (12 12± 796 )斑点形成细胞数 (SFC) / 10 6外周血单个核细胞(PBMC)和 (182± 2 0 3)SFC/ 10 6PBMC ,识别肽段库的个数 (间接反应了细胞毒性T淋巴细胞应答的宽度 )分别为 3 0± 0 8和 0 8± 0 7,LTNP组显著高于AIDS组。CD 8T细胞应答的强度和宽度与CD 4 T细胞计数呈正相关 ,与病毒载量呈负相关。结论　欧美流行株与我国病毒株之间具有交叉反应性 ,HIV 1gag特异性CD 8T细胞应答在阻止疾病进展中可能发挥重要作用。     

230例HIV/AIDS患者肝脏损害的临床研究

目的探讨艾滋病病毒/艾滋病(HIV/AIDS)患者的肝脏损害情况。方法检测230例住院的HIV/AIDS患者乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)感染标志,分为单纯HIV感染、HIV/HCV、HIV/HBV、HIV/HCV/HBV合并感染4组,对这4组患者的肝脏病理、CD4 淋巴细胞计数、肝功能、凝血酶原时间及活动度进行回顾性分析。结果HIV合并HCV感染的患者住院时的CD4 计数216±195/mm3,与单纯HIV感染者及合并HBV感染者比较有显著性差异;单纯HIV感染者的肝脏病理呈非特异性改变,丙氨酸转氨酶(ALT)、天冬酸转氨酶(AST)呈轻度升高,白蛋白(ALB)降低;HIV/HCV、HIV/HBV合并感染者的肝脏损害表现为肝脏病理的炎症分级和纤维化程度比单纯HIV感染者高,ALT、AST呈轻度升高,ALB降低,以HIV/HBV合并感染者为明显,达27.7±7.5g/L;HIV/HCV/HBV合并感染者的肝脏损害最严重,表现为总胆红素(TB)明显增高,达61.0±100.6μmol/mm3,ALT、AST呈轻至中度升高,ALB降低,胆碱脂酶明显降低,凝血酶原时间明显延长,除ALB外,与单纯HIV感染者比较差异有显著性意义。结论单纯HIV感染患者的肝脏损害呈非特异性,HIV合并HCV或/和HBV感染,可加重患者的肝脏损害,以同时合并HCV、HBV感染者为明显。     

结核分枝杆菌与艾滋病病毒双重感染患者抗结核治疗期间死亡的影响因素分析

目的 了解Mtb与HIV双重感染患者抗结核治疗期间死亡相关影响因素。 方法 对2007-2008年期间,广西、四川、湖南三省（自治区）共6个县诊治Mtb与HIV双重感染患者抗结核治疗期间死亡情况进行分析。共观察330例患者,抗结核治疗期间死亡33例。使用SAS 9.2软件,分析患者体质量、CD4⁺ T淋巴细胞水平、接受抗病毒治疗时间、HIV感染途径、HIV感染年限、结核病类型、机会感染等因素对Mtb与HIV双重感染患者抗结核治疗期间死亡状况的影响,P<0.05为差异有统计学意义。 结果 Mtb与HIV双重感染患者抗结核治疗期间病死率为10.0%（33/330）。对死亡相关影响因素分析发现：运用logistic回归进行统计学分析,CD4⁺ T淋巴细胞水平未对患者的病死率产生影响（Wald χ²=0.5774,P=0.4473,OR值0.858,95%CI值0.578～1.274）;未接受抗病毒治疗的患者的病死率是接受抗病毒治疗的患者的病死率的7.612倍（Wald χ²=14.8539,P<0.001,OR值7.612,95%CI值2.712～21.369）,是否接受抗病毒治疗是患者病死率的影响因素;性传播组病死率（6.7%,14/210）与静脉吸毒组病死率（16.1%,19/118）比较,静脉吸毒组病死率较高,采用Fisher确切概率法进行统计学分析,P<0.05;涂阳肺结核组、涂阴肺结核组、肺结核组、肺结核合并肺外结核组、单纯肺外结核组病死率（分别为：20.9%,18/86;8.0%,14/174;11.7%,27/230;16.7%,5/30;1.4%,1/70）比较,涂阳肺结核及肺结核合并肺外结核组病死率较高,χ²值分别为17.8685和7.9687,P值均<0.05。 结论 结核病变程度、患者机能状况是影响Mtb与HIV双重感染患者病死状况的主要因素。     

慢性丙型肝炎患者病毒因素及宿主细胞免疫对干扰素治疗应答的影响

目的：探讨丙型肝炎病毒（HCV）因素及机体细胞免疫因素对干扰素疗效的影响。方法：对40例慢性丙型肝炎患者进行干扰素治疗，分析HCV基因型，准种多样性，血清HCV RNA水平及肝组织HCV特异性细胞毒T淋巴细胞（CTL）活性与干扰素应答的关系。结果：经过6个月的干扰素治疗，21例获得治疗终点应答，其中10例呈持续应答，19例无应答，HCV1型患者应答率（43．3％）明显低于非1型患者（80％，P＜0．05），应答患者中治疗前血清HCV准种数目及HCVRNA水平明显低于无应答患者（P＜0．05，P＜0．01），而其肝组织HCV特异性CTL活性阳性率则显著高于无应答者（P＜0．05），结论：病毒因素和宿主因素均是影响慢性丙型肝炎干扰素治疗效果的重要因素，非1型感染，低准种数目，低病毒血症水平及肝组织HCV特异性CTL活性阳性者预示对干扰素应答良好。     

丙型肝炎病毒和人类免疫缺陷病毒合并感染者肝组织病理学观察

丙型肝炎病毒（HCV）和人类免疫缺陷病毒（HIV）合并感染的情况十分多见，在经输血或单采血浆而感染HIV者中甚至高达90％以上。高效抗逆转录病毒治疗（HAART）的应用使HIV相关的综合征和病死率大大下降。却使HCV慢性感染在共感染者中的致病作用日益凸现。本研究旨在通过比较HIV／HCV共感染组与HCV单纯感染组的肝组织病理学改变，观察HIV／HCV合并感染者肝组织的病理学特征。     

Characterization of humoral and cell-mediated immune responses directed against hepatitis C virus F protein in subjects co-infected with hepatitis C virus and HIV-1

BACKGROUND: Hepatitis C virus (HCV) F protein is encoded in an alternate reading frame overlapping the core protein region. Its precise sequence, biological function and mode of expression are currently unclear. This study was conducted to examine the prevalence and characteristics of host humoral and cell-mediated immune responses directed against F protein in patients co-infected with HCV and HIV-1. METHODS: Mutations were introduced to allow the expression of HCV-1a F protein in the absence of core. This recombinant and a truncated form lacking the first 11 amino acid residues shared with core were expressed in Escherichia coli, and their amino acid sequences were verified by mass spectrometry. Vaccinia-F protein recombinants were used to test F protein-specific cytotoxic T lymphocyte (CTL) activity. The binding of F protein-derived peptides to HLA-A*0201 was studied to identify putative CTL epitopes. RESULTS: Sera from 23 of 39 patients infected with various HCV genotypes recognized the truncated form, including 13 of 25 subjects co-infected with HIV-1, indicative of antigenic crossreactivity and consistent with the conservation of F protein coding sequences between HCV genotypes. Crossreactive F protein-specific CTL precursors were detected in nine of 11 HCV-infected subjects, including seven of nine patients co-infected with HCV and HIV-1. Finally, three novel putative HLA-A*0201-restricted CTL epitopes were identified. CONCLUSION: These results indicate that patients co-infected with HCV and HIV-1 can mount immunoglobulin and CTL responses directed against HCV F protein that are fully comparable in scope and magnitude with those observed in individuals infected with HCV alone.     

HCV/HIV-1合并感染者血清GP73变化特征

目的观察合并艾滋病的丙型肝炎患者血清GP73水平的变化特征。方法本研究主要观察了3个人群:50例健康体检者;22例AIDS患者,其中10例患者合并慢性HCV感染;28例没有合并症的单纯慢性丙型肝炎的患者。血清GP73采用标准ELISA法检测。结果与健康对照人群(36.18±12.26)ng/mL相比,慢性丙型肝炎患者血清GP73(79.73±43.91)ng/mL显著升高(P<0.0001);而AIDS患者血清GP73(122.6±65.51)ng/mL较单纯慢性丙型肝炎患者也显著升高(P=0.008)。对22例AIDS患者血清GP73分析显示,合并丙型肝炎的患者(98.32±60.14)ng/mL,低于单纯HIV-1感染的患者(142.8±65.23)ng/mL,但两组之间差异并无统计学意义(t=1.65,P=0.11)。AIDS患者的血清GP73水平与CD4+T和CD8+T细胞的绝对计数呈显著负相关(r值分别为-0.58和-0.49),而与HIV RNA拷贝数成正相关(r=0.61,P=0.0026)。结论合并HIV-1感染可以显著增加丙肝患者血清GP73水平。检测血清GP73水平的变化在一定程度上可以反映HIV-1复制情况及免疫状态的变化。     

河北省HIV-1感染者中HCV和HBV合并感染状况调查

目的了解河北省艾滋病病毒Ⅰ型(HIV-1)感染者中,丙型肝炎病毒(HCV)、乙型肝炎(乙肝)病毒(HBV)的感染状况。方法采集了HIV-1感染者的抗凝全血样品,进行了HCV抗体和乙肝病毒表面抗原(HBsAg)的检测。结果 147例HIV-1感染者中,HCV感染率为17.7%(26/147),HBV感染率为15.0%(22/147),HCV/HBV混合感染率为3.4%(5/147)。在HIV-1感染者中,HCV的感染率在注射吸毒感染者中为100%(6/6),血液途径感染者中为73.3%(11/15),性感染者中为6.3%(7/111),不同感染途径间的差异有统计学意义(P<0.001);女性高于男性(P=0.002);低文化程度的感染者中感染率较高,文化程度方面差异有统计学意义(P<0.01)。在HIV-1感染者中,HBV的感染率小年龄组较高(P<0.05)。结论在HIV感染人群中,有较高的HCV和HBV感染率。     

乙型和丙型肝炎病毒合并感染患者的临床特征及抗病毒治疗的应答

目的 探讨HBV和HCV合并感染患者的临床特征及对聚乙二醇干扰素α-2a(PEGIFNα-2a)联合利巴韦林抗病毒疗效的影响.方法 对39例HBV和HCV合并感染患者的流行病学和病毒学资料进行回顾性分析,并观察PEGIFNα-2a联合利巴韦林治疗的病毒学应答情况.数据行χ~2检验和t检验.结果 39例HBV和HCV合并感染患者中,HCV优势株型35例,占89.7%;HBV和HCV混合优势株型4例,占10.3%.39例合并感染组患者HBeAg阳性率为15.4%,明显低于42例单纯HBV感染者的45.3%(χ~2=8.446,P=0.004).合并感染组患者的HBV DNA平均值为(4.6±O.9)lg拷贝/mL,,明显低于单纯HBV感染组的(5.9±1.2)lg拷贝/mL(t=5.544,P<0.01).在29例基因1型患者中,合并感染组的部分早期病毒学应答率为51.7%,明显高于25例单纯HCV感染组的24.0%(χ~2=4.432,P=0.037);治疗结束时病毒学应答率为93.1%,也明显高于HCV感染组的56.0%(χ~2=10.112,P=0.001);复发率为55.6%,也明显高于HCV感染组的21.4%(χ~2=4.360,P=0.037).非基因1型患者中,合并感染组与HCV感染组的快速病毒学应答、完全早期病毒学应答、部分早期病毒学应答、治疗结束时病毒学应答、持续病毒学应答和复发率相比差异无统计学意义(P>0.05).合并感染组39例患者中有15例出现不良反应,占38.5%,单纯HCV感染组25例患者中有6例出现不良反应,占17.6%(χ~2=3.851,P=0.049).结论 HBV和HCV合并感染以HCV为优势病毒株,HBV复制受抑制.与单纯HCV感染相比.基因1型患者部分早期病毒学应答、治疗结束时病毒学应答和复发率高,持续病毒学应答相似;合并感染对非基因1型病毒学应答率无影响.     

HIV long-term non-progressors maintain brisk CD8 T cell responses to other viral antigens

OBJECTIVE: To examine the specificity of heightened CD8 cell responses in HIV-1-infected long-term non-progressors. DESIGN: Cross-sectional study examining CD8 cell responses to hepatitis C virus (HCV) peptides in HCV-HIV LTNP (n = 6), HCV-HIV progressors (n = 11), HCV singly infected patients (n = 32), HCV singly infected patients with self-limited disease (n = 10), HIV singly infected progressors (n = 7) and HCV-negative, HIV-negative controls (n = 10). METHODS: The frequency of HCV-reactive interferon gamma-producing cells in peripheral blood was assayed by enzyme linked immunospot assay using a panel of 61 HCV-1-derived peptides. RESULTS: Five of six HCV-HIV LTNP had HCV-specific CD8 responses. In contrast, responses were observed in 2 of 32 HCV singly infected patients, 2 of the 10 HCV singly infected patients with self-limited disease, and 0 of 11 HCV-HIV progressors (P < 0.001). Both frequency of HCV-specific CD8 cells and number of HCV peptides recognized were greater in HCV-HIV LTNP than in other groups. CONCLUSIONS: HIV-infected LTNP maintain heightened CD8 cell responses to HCV in addition to heightened HIV specific responses. Common mechanisms may underlie preservation of CD8 immune responses in these individuals. An improved understanding of these mechanisms will help to gain insight into protective antiviral immunity as well as to the means whereby these viruses impair host defenses.     

Serum cortisol predicts death and critical disease independently of CRB-65 score in community-acquired pneumonia: a prospective observational cohort study

Background

Co-infection with hepatitis C (HCV) is very common in human immunodeficiency virus 1 (HIV-1) infected patients. Although HIV co-infection clearly accelerates progression of HCV-related fibrosis and liver disease, controversy remains as to the impact of HCV on HIV disease progression in co-infected patients. HIV can cause immune dysfunction, in which the regulatory function of T helper (Th) cells is very essential. Moreover, cytokines derived from Th cells play a prominent role in viral infection. Investigating the functional changes of Th1 and Th2 cells in cytokine level can improve the understanding of the effect of co-infected HCV on HIV infection.

Methods

In this study, we measured the baseline Th1/Th2 cytokine concentration in sera by using flow cytometry in HIV/HCV co-infection, HIV mono-infection, HCV mono-infection, and healthy control group, as well as the dynamic changes of these cytokine levels after receiving highly active antiretroviral therapy (HAART).

Results

The ratio of Th1 and Th2 cytokine concentration in HIV/HCV co-infection was higher than HCV mono-infection and healthy control group, while lower than HIV mono-infection group. After HAART was initiated, the Th1/Th2 ratio of HIV/HCV co-infection group decreased to the same level of healthy control, while HIV mono-infection group was still higher than the control group.

Conclusions

There was no significant evidence showing co-infected with HCV had negative effect on HIV related diseases. However, co-infected with HCV can decrease Th1/Th2 ratio by affecting Th1 cytokine level, especially the secretion of IFN-??. With the initiation of HAART, Th1 and Th2 cytokine levels were progressively reduced. HIV was the main stimulating factor of T cells in HIV/HCV co-infection group.     

Synergistic effect of combined HIV/HCV immunogens: a combined HIV-1/HCV candidate vaccine induces a higher level of CD8+ T cell-immune responses in HLA-A2.1 mice

Dual infections with HIV-1 and Hepatitis C virus (HCV) may proceed in concert to cause severe disease. HIV positive individuals that become infected with HCV advance more rapidly to AIDS than those that are infected with HIV-1 alone. In this study, HLA-A2.1 mice were immunized with a combination vaccine including HIV and HCV immunogens (polycistronic DNA + proteins) or vaccine containing either HIV or HCV immunogens. Mice immunized with the combined HIV/HCV regimen had similar antibody titers as the group receiving either the HIV-1 or HCV only regimen. Proliferative immune responses showed that mice receiving the combined HIV/HCV vaccine exhibited a three fold higher stimulation index (SI) to gp120 than mice immunized with the vaccine containing HIV alone. To determine whether our vaccine strategy induced Th1 or Th2 immune responses, IFN-gamma and IL-4/IL-5 were measured. The combined HIV/HCV vaccine induced a higher level of Th1 responses to HIV-1 gag protein compared with the other groups, as measured by IFN-gamma production. Interestingly, detection of IFN-gamma by ELISPOT assay demonstrated that the combined HIV/HCV vaccine group had increased numbers of spot forming cells (SFC) to HIV-gp120 peptides when compared to that of the HIV-1 only vaccine group. The combined HIV/HCV vaccine group also showed an increase in SFC to HCV-core peptides in comparison with the group receiving the HCV only vaccine. Intracellular IFN-gamma staining confirmed the ELISPOT results and demonstrated that the combined HIV/HCV group had significantly higher percentages of HIV and HCV-specific CD8+ T cells in comparison to the groups receiving the HIV or HCV vaccines. These results suggest a new approach to maximize vaccine efficacy against HIV and HCV.     

The GNB3 C825T polymorphism affects response to HCV therapy with pegylated interferon in HCV/HIV co-infected but not in HCV mono-infected patients

BACKGROUND/AIMS: Response to HCV treatment with pegylated interferon-alpha is variable but might at least in part depend on genetic host factors. The G protein beta3 unit (GNB3) C825T polymorphism has been shown to affect treatment response in HCV mono-infection. Here, we analyzed the impact of the GNB3 genotype in the context of HCV/HIV co-infection. METHODS: HIV/HCV co-infected (n=112) and HCV mono-infected patients (n=150), receiving therapy with pegylated IFN-alpha/ribavirin, were enrolled into this study. Furthermore, we analyzed 220 healthy and 92 HIV mono-infected patients. GNB3 genotype was defined and correlated with respect to treatment response. RESULTS: GNB3 genotype distribution differed significantly between HIV/HCV co-infected patients and HIV-positive/HCV-negative (p=0.0002) or healthy controls (p=0.03). Patients with a GNB3 CC genotype had significantly lower SVR rates as compared to carriers of a non-CC genotype (52% versus 77%; p=0.018). In a logistic regression analysis the GNB3 genotype and the HCV genotype were significantly associated with response to treatment (p=0.018). In contrast to HIV/HCV co-infected patients, GNB3 genotype did not affect response to treatment in HCV mono-infected patients. CONCLUSIONS: The GNB3 825 CC genotype is associated with poor SVR rates in HIV/HCV co-infected patients. This underlines the impact of genetic host factors for treatment response.     

Prevalence of hepatitis C in an ethnically diverse HIV-1-infected cohort in south London

OBJECTIVES: There is limited information on the prevalence of and risk factors for hepatitis C virus (HCV) infection among HIV-1-infected patients in the UK. Our objective was to determine the prevalence of HCV infection among an ethnically diverse cohort of HIV-infected patients in south London, and to extrapolate from these data the number of co-infected patients in the UK. METHODS: A total of 1017 HIV-1-infected patients who had attended King's College Hospital HIV clinic between September 2000 and August 2002 were screened for HCV antibody using a commercial enzyme-linked immunosorbent assay (ELISA). Positive results were confirmed by polymerase chain reaction (PCR) or recombinant immunoblot assay. Demographic, clinical and laboratory data were obtained from the local computerized database and medical records. We applied our HCV prevalence rates in the different HIV transmission groups to the estimated number of HIV-infected persons in these groups in the UK, to obtain a national estimate of the level of HIV-HCV co-infection. RESULTS: Of the 1017 HIV-1-infected patients, 407 (40%) were white men, 158 (15.5%) were black African men, 268 (26.3%) were black African women, and 61 (6%) and 26 (2.6%) were black Caribbean men and women, respectively. Heterosexual exposure was the most common route of HIV acquisition (53.5%), followed by men having sex with men (36.9%), and current or previous injecting drug use (IDU) (7.2%). The overall prevalence of HCV co-infection was 90/1017 (8.9%), but this varied substantially according to route of transmission, from 82.2% among those with a history of IDU (which accounted for 67% of all HCV infections), to 31.8% in those who had received blood products, to 3.5% and 1.8% in those with homosexually and heterosexually acquired infection, respectively. Multivariate logistic regression analysis identified several independent risk factors for HCV infection: a history of IDU [odds ratio (OR) = 107.2; 95% confidence interval (CI) = 38.5-298.4], having received blood products (OR = 16.5; 95% CI = 5.1-53.7), and either being from a white ethnic group (OR = 4.3; 95% CI = 1.5-12.0) or being born in Southern Europe (OR = 6.7; 95% CI = 1.5-30.7). Based on the 35,473 known HIV-1-infected persons in the UK and the 10 997 estimated to be unaware of their status, we projected that there are at least 4136 HIV-HCV co-infected individuals in the UK and 979 who are unaware of their status. CONCLUSIONS: Overall, 9% of our cohort was HIV-HCV co-infected. The prevalence was highest among intravenous drug users (82%), who accounted for most of our HCV cases, and lowest among heterosexual men and women from sub-Saharan Africa and the Caribbean [< 2%]. Our estimate that a significant number of co-infected persons may be unaware of their HIV and HCV status, highlights an urgent need to increase the uptake of HCV and HIV testing, particularly among injecting drug users, to reduce the risk of onward transmission.