• 1 Malnutrition in HIV infection. 复制标题 收藏 收藏

    【HIV感染中的营养不良。】 复制标题 收藏 收藏
    DOI:10.1016/s0889-8553(05)70301-0 复制DOI
    作者列表:Babameto G,Kotler DP
    BACKGROUND & AIMS: Malnutrition is a common complication of HIV infection and plays a significant and independent role in morbidity and mortality. Many studies have been conducted to assess the appropriate role of nutrition in the clinical management of HIV infection. The complex nature of AIDS wasting, however, requires individualized strategies when providing nutritional support. Algorithms to assist in the diagnosis and treatment of malnutrition in HIV infection serve as general guidelines.

    背景与目标: 营养不良是艾滋病毒感染的常见并发症,在发病率和死亡率中起着重要而独立的作用。已经进行了许多研究,以评估营养在HIV感染的临床管理中的适当作用。然而,浪费艾滋病的复杂性,在提供营养支持时需要个性化的策略。辅助诊断和治疗HIV感染中营养不良的算法为一般准则。

  • 【HIV-1 RNA的贩运是由异质核糖核蛋白A2的表达介导的,并且对病毒的组装也有影响。】 复制标题 收藏 收藏
    DOI:10.1111/j.1600-0854.2006.00461.x 复制DOI
    作者列表:Lévesque K,Halvorsen M,Abrahamyan L,Chatel-Chaix L,Poupon V,Gordon H,DesGroseillers L,Gatignol A,Mouland AJ
    BACKGROUND & AIMS: :Few details are known about how the human immunodeficiency virus type 1 (HIV-1) genomic RNA is trafficked in the cytoplasm. Part of this process is controlled by the activity of heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2). The role of hnRNP A2 during the expression of a bona fide provirus in HeLa cells is investigated in this study. Using immunofluorescence and fluorescence in situ hybridization techniques, we show that knockdown of hnRNP A2 expression in HIV-1-expressing cells results in the rapid accumulation of HIV-1 genomic RNA in a distinct, cytoplasmic space that corresponds to the microtubule-organizing center (MTOC). The RNA exits in the nucleus and accumulates at the MTOC region as a result of hnRNP A2 knockdown even during the expression of a provirus harboring mutations in the hnRNP A2-response element (A2RE), the expression of which results in nuclear retention of genomic RNA. We also demonstrate that hnRNP A2 expression is required for downstream trafficking of genomic RNA from the MTOC in the cytoplasm. Genomic RNA localization at the MTOC that was both the result of hnRNP A2 knockdown and the overexpression of Rab7-interacting lysosomal protein had little effect on pr55Gag synthesis but negatively influenced virus production and infectivity. These data indicate that altered HIV-1 genomic RNA localization modulates viral assembly and that the MTOC serves as a central site to which HIV-1 genomic RNA converges following its exit from the nucleus, with the host protein, hnRNP A2, playing a central role in taking it to and from this site in the cell.
    背景与目标: 关于人类免疫缺陷病毒1型(HIV-1)基因组RNA如何在细胞质中运输的信息鲜为人知。该过程的一部分由异质核糖核蛋白A2(hnRNP A2)的活性控制。这项研究调查了hnRNP A2在HeLa细胞中表达真正的原病毒的过程中的作用。使用免疫荧光和荧光原位杂交技术,我们显示敲低表达HIV-1的细胞中hnRNP A2表达的表达导致HIV-1基因组RNA在与微管组织中心相对应的独特细胞质空间中的快速积累( MTOC)。即使hnRNP A2反应元件(A2RE)中携带有突变的原病毒表达,RNA仍会通过hnRNP A2敲除而留在细胞核中并在MTOC区域积聚,其表达会导致基因组RNA的核保留。我们还证明hnRNP A2表达是从细胞质MTOC下游运输基因组RNA所必需的。基因组RNA在MTOC处的定位既是hnRNP A2敲除的结果,又是与Rab7相互作用的溶酶体蛋白的过表达,对pr55Gag的合成影响很小,但对病毒的产生和感染性产生负面影响。这些数据表明,改变的HIV-1基因组RNA定位可调节病毒装配,MTOC充当HIV-1基因组RNA从细胞核退出后向其汇聚的中心位点,宿主蛋白hnRNP A2发挥着核心作用。将其带入和移出该单元格中的此站点。
  • 【接受高活性抗逆转录病毒疗法治疗的替诺福韦富马酸二甲氧呋酯(TDF)暴露和TDF未暴露的HIV感染门诊患者的低血磷评估。】 复制标题 收藏 收藏
    DOI:10.1111/j.1468-1293.2006.00407.x 复制DOI
    作者列表:Buchacz K,Brooks JT,Tong T,Moorman AC,Baker RK,Holmberg SD,Greenberg A,HIV Outpatient Study (HOPS) Investigators.
    BACKGROUND & AIMS: OBJECTIVES:Cases of hypophosphataemia (often coincident with renal dysfunction) have been reported in HIV-infected patients taking tenofovir disoproxil fumarate (TDF), but randomized placebo-controlled trials of HIV-infected persons with normal baseline renal function have found a comparable incidence of hypophosphataemia in the TDF and placebo groups. We assessed the incidence of grade 2 and higher hypophosphataemia in the HIV Outpatient Study (HOPS). METHODS:We analysed a prospective cohort of patients who initiated either a TDF-containing highly active antiretroviral therapy (HAART) regimen [TDF-exposed (TDF+) group; n = 165] or a TDF-sparing HAART regimen [TDF-unexposed (TDF-) group; n = 90], and who had normal baseline phosphate and creatinine values. RESULTS:The TDF+ and TDF- groups had comparable median follow-up times (10.9 vs 8.8 months, respectively; P = 0.18) and number of phosphate measurements (median = 3 for both) and were similar on most clinical and demographic factors. During follow up, 12.7% of TDF+vs 6.7% of TDF-patients developed grade 2 hypophosphataemia (2.0-2.4 mg/dL), and 2.4% of TDF+ patients vs 0% of TDF-patients developed grade 3 hypophosphataemia (1.0-1.9 mg/dL); none developed grade 4 hypophosphataemia (<1.0 mg/dL). The incidence of grade 2 or higher hypophosphataemia was 16.7 per 100 person-years among TDF+ patients vs 8.0 per 100 person-years among TDF-patients (P = 0.11). CONCLUSIONS:The incidence of hypophosphataemia was somewhat elevated in HOPS patients who took TDF-containing HAART compared with those who took TDF-sparing HAART during the first 1 to 2 years of observation, but the difference was not statistically significant. Longer follow-up of a larger population is needed to determine if this trend towards an association achieves statistical significance and to evaluate the clinical consequences of hypophosphataemia.
    背景与目标: 目的:已经报道了接受替诺福韦二富马酸富马酸酯(TDF)感染HIV的患者发生低血磷的情况(通常与肾功能不全同时发生),但基线肾功能正常的HIV感染者的随机安慰剂对照试验发现TDF和安慰剂组的低磷血症。我们在HIV门诊研究(HOPS)中评估了2级和更高的低血磷的发生率。
    方法:我们分析了开始采用含TDF的高活性抗逆转录病毒疗法(HAART)方案[TDF暴露(TDF)组)的患者的前瞻性队列研究。 n = 165]或保留TDF的HAART方案[未暴露TDF(TDF-)的组; n = 90],并且基线磷酸盐和肌酐值正常。
    结果:TDF和TDF-组的中位随访时间(分别为10.9和8.8个月; P = 0.18)和磷酸盐测量次数(两者的中位数= 3)具有可比性,并且在大多数临床和人口统计学因素上相似。在随访期间,TDF的12.7%与TDF的患者的6.7%发生了2级低血磷(2.0-2.4 mg / dL),TDF的2.4%vs TDF的患者中出现了3级的低血磷(1.0-1.9 mg) / dL);没有一个发生4级低血磷(<1.0 mg / dL)。 TDF患者中2级或更高水平低血磷的发生率为每100人年16.7人,而TDF患者为每100人年8.0人(P = 0.11)。
    结论:在观察的头1至2年中,与含TDF的HAART的HOPS患者相比,接受含TDF的HAART的HOPS患者的低磷酸盐血症发生率有所升高,但差异无统计学意义。需要对更大的人群进行更长时间的随访,以确定这种联系趋势是否达到统计学意义并评估低血磷的临床后果。
  • 【MAP 30:一种新的HIV-1感染和复制抑制剂。】 复制标题 收藏 收藏
    DOI:10.1016/0014-5793(90)80438-o 复制DOI
    作者列表:Lee-Huang S,Huang PL,Nara PL,Chen HC,Kung HF,Huang P,Huang HI,Huang PL
    BACKGROUND & AIMS: :A new inhibitor of human immunodeficiency virus (HIV) has been isolated and purified to homogeneity from the seeds and fruits of the Momordica charantia. This compound, MAP 30 (Momordica Anti-HIV Protein), is a basic protein of about 30 kDa. It exhibits dose-dependent inhibition of cell-free HIV-1 infection and replication as measured by: (i) quantitative focal syncytium formation on CEM-ss monolayers; (ii) viral core protein p24 expression; and (iii) viral-associated reverse transcriptase (RT) activity in HIV-1 infected H9 cells. The doses required for 50% inhibition (ID50) in these assays were 0.83, 0.22 and 0.33 nM, respectively. No cytotoxic or cytostatic effects were found under the assay conditions. These data suggest that MAP 30 may be a useful therapeutic agent in the treatment of HIV-1 infections. The sequence of the N-terminal 44 amino acids of MAP 30 has been determined.
    背景与目标: :已从苦瓜种子和果实中分离出一种新的人类免疫缺陷病毒(HIV)抑制剂并将其纯化至同质。该化合物MAP 30(Momordica抗HIV蛋白质)是约30 kDa的碱性蛋白质。它通过以下方式表现出对无细胞HIV-1感染和复制的剂量依赖性抑制作用:(i)在CEM-ss单层上的定量局灶性合胞体形成; (ii)病毒核心蛋白p24表达; (iii)HIV-1感染的H9细胞中的病毒相关逆转录酶(RT)活性。在这些试验中,抑制50%(ID50)所需的剂量分别为0.83、0.22和0.33 nM。在测定条件下未发现细胞毒性或细胞抑制作用。这些数据表明,MAP 30可能是治疗HIV-1感染的有用治疗剂。已经确定了MAP 30的N-末端44个氨基酸的序列。
  • 【在西西里岛东部卡塔尼亚生活的哥伦比亚和多米尼加女性性工作者中,艾滋病毒和其他性传播疾病的流行。】 复制标题 收藏 收藏
    DOI:10.1007/s10903-006-9002-1 复制DOI
    作者列表:Nigro L,Larocca L,Celesia BM,Montineri A,Sjoberg J,Caltabiano E,Fatuzzo F,Unit Operators Group.
    BACKGROUND & AIMS: INTRODUCTION:STDs are a significant cause of illness throughout the world. Female sex workers (FSWs) are commonly perceived as belonging to a social group which may engage in high-risk behaviour for acquiring or transmitting HIV and other STDs. The number of immigrant women engaged in sex work has increased in Catania, Sicily, over the last 10 years. This study aims to estimate the prevalence of HIV, HBV, HCV and syphilis among Colombian and Dominican FSWs. METHODS:In total 118 (63.78%) of the FSWs contacted in the course of the project agreed to participate in the study. All women enrolled were counselled on STDs/HIV, safer sex practices and the use of condoms. Blood samples were taken and tested for HIV, HBV, HCV and syphilis. RESULTS:Of the 118 FSWs enrolled, all were negative for both HIV and HCV infection. Two women (1.6%) were positive for hepatitis B (HbsAg). Syphilis testing by VDRL showed three positive results (2.5%), which was confirmed by TPHA. DISCUSSION:This study showed that HIV, HBV, HCV and syphilis seroprevalence among Colombian and Dominican FSWs remains low or very rare. It also indicates that these women were healthy when they arrived in Italy and that condom use with clients is high.
    背景与目标: 简介:性病是世界范围内引起疾病的重要原因。女性性工作者(FSWs)通常被认为属于一个社会群体,该群体可能会为获取或传播艾滋病毒和其他性传播疾病而从事高风险行为。在过去的十年中,西西里岛卡塔尼亚从事性工作的移民妇女人数有所增加。这项研究的目的是估计哥伦比亚和多米尼加的FS​​W中HIV,HBV,HCV和梅毒的患病率。
    方法:在该项目过程中,总共有118名(63.78%)的FSW同意参与研究。为所有入选妇女提供性传播疾病/艾滋病毒,更安全的性行为和使用安全套方面的咨询。抽取血样并测试HIV,HBV,HCV和梅毒。
    结果:在118个FSW中,所有的HIV和HCV感染均为阴性。两名女性(1.6%)的乙型肝炎(HbsAg)阳性。 VDRL进行的梅毒测试显示三项阳性结果(2.5%),这已被TPHA证实。
    讨论:这项研究表明,哥伦比亚和多米尼加地区FSW中的HIV,HBV,HCV和梅毒血清阳性率仍然很低或非常罕见。这也表明这些妇女到达意大利后就很健康,而且与客人一起使用避孕套的比例很高。
  • 【巴巴多斯黑人中严重的原发性HIV-1感染。】 复制标题 收藏 收藏
    DOI:10.1258/0956462971920325 复制DOI
    作者列表:Hudson CP,Levett PN,Edwards CN,Moosai R,Roach TC
    BACKGROUND & AIMS: :Descriptions of primary HIV-1 infection have so far been based on Caucasians living in industrialized nations. Due to studies of leptospirosis in the predominantly black population of Barbados, serum was available for patients admitted with acute febrile illnesses to the Queen Elizabeth Hospital (QEH). By searching the medical records of 510 adult patients with known HIV-1 infection we identified 10 patients who had stored serum from an admission for an acute febrile illness that predated or coincided with their first HIV-1-positive test. Serological testing confirmed primary HIV-1 infection in 9 and was suggestive in the 10th patient. The clinical features of these 10 patients were in keeping with previous descriptions of primary HIV-1 infection but differed from leptospirosis cases seen at the QEH. One patient died during his seroconversion illness and another died 3 months after seroconversion. The findings suggest that severe primary HIV-1 infection could be a relatively uncommon occurrence, that the condition may be misdiagnosed, and that cases may not occur until the AIDS epidemic is established. :A retrospective review was conducted of the medical records of 510 HIV-1-positive adult patients who had attended the Queen Elizabeth Hospital (QEH) to determine whether any had been admitted for an illness compatible with a diagnosis of primary HIV-1 infection. A serum bank, created from patients who had been admitted with acute febrile illnesses and investigated for leptospirosis, provided serological evidence for primary HIV-1 infection in 10 patients. Serological testing of the serum samples confirmed primary HIV-1 infection in nine patients and was suggestive in the tenth. The clinical features of the 10 patients fit the earlier descriptions of primary HIV-1 infection, but differed from the leptospirosis cases seen at the QEH. One patient died during his seroconversion illness and another died 3 months after seroconversion. These findings suggest that severe primary HIV-1 infection could be a relatively uncommon occurrence, that the condition may be misdiagnosed, and that cases may not occur until the AIDS epidemic is established.
    背景与目标: :到目前为止,主要针对HIV-1感染的描述都是基于生活在工业化国家中的高加索人。由于对巴巴多斯主要是黑人人群的钩端螺旋体病进行了研究,因此伊丽莎白女王医院(QEH)接受了急性发热性疾病的患者可获得血清。通过搜索510例已知HIV-1感染的成年患者的病历,我们确定了10例在首次发热HIV-1阳性测试之前或与其同时发生的急性发热疾病患者入院时就储存了血清的患者。血清学检查证实了9例原发性HIV-1感染,并提示第10例患者。这10例患者的临床特征与原发性HIV-1感染的先前描述相符,但与QEH所见的钩端螺旋体病病例有所不同。一名患者在血清转化疾病中死亡,另一名患者在血清转化后3个月死亡。研究结果表明,严重的原发性HIV-1感染可能是相对罕见的事件,该病可能被误诊,只有在AIDS流行之前,病例才可能发生。
    :回顾性分析了510例曾在伊丽莎白女王医院(QEH)住院的HIV-1阳性成年患者的病历,以确定是否有人因与原发性HIV-1感染诊断相符的疾病而入院。由被接纳患有急性发热性疾病的患者创建的血清库,并研究了钩端螺旋体病,为10例患者的原发性HIV-1感染提供了血清学证据。血清样本的血清学检测证实了9名患者的原发性HIV-1感染,而第十名患者则具有启发性。这10例患者的临床特征符合原发性HIV-1感染的早期描述,但与QEH所见的钩端螺旋体病病例有所不同。一名患者在血清转化疾病中死亡,另一名患者在血清转化后3个月死亡。这些发现表明,严重的原发性HIV-1感染可能是相对罕见的事件,可能会误诊该病,并且直到艾滋病流行才可能发生。
  • 【扎西他滨。在管理HIV感染方面其药效学和药代动力学特性以及临床功效的更新。】 复制标题 收藏 收藏
    DOI:10.2165/00003495-199753060-00009 复制DOI
    作者列表:Adkins JC,Peters DH,Faulds D
    BACKGROUND & AIMS: :Zalcitabine is a dideoxynucleoside antiretroviral agent that is phosphorylated to the active metabolite 2',3'-dideoxycytidine 5'-triphosphate (ddCTP) within both uninfected and HIV-infected cells. At therapeutic concentrations, ddCTP inhibits HIV replication by inhibiting the enzyme reverse transcriptase and terminating elongation of the proviral DNA chain. The results of 3 large pivotal trials comparing zidovudine monotherapy with combination therapy have now clearly established that zalcitabine plus zidovudine combination with an improvement in viral load and CD4+ cell count compared with zidovudine monotherapy. More recently, clinical end-point and surrogate marker data have established the efficacy of zalcitabine in combination with the protease inhibitor saquinavir in zidovudine-experienced patients. Other studies have demonstrated the utility of zalcitabine in combination with ritonavir and the nucleoside analogue lamivudine. Importantly, early use of zalcitabine in the treatment sequence does not appear to limit the therapeutic efficacy of subsequent therapy with other nucleoside analogues such as lamivudine. Peripheral neuropathy is the most frequent dose-limiting adverse effect associated with zalcitabine therapy and is generally reversible on discontinuation of treatment. Stomatitis and mouth ulcers may occur frequently with zalcitabine therapy but tend to resolve with continuing treatment. Haematological toxicity, which is a common adverse effect associated with zidovudine, is reported infrequently with zalcitabine. Overall, combination therapy with zalcitabine plus zidovudine or saquinavir has been shown to have a tolerability profile comparable to that of either agent alone, although treatment with zidovudine plus zalcitabine was associated with a significant increase in the incidence of haematological toxicity compared with zidovudine monotherapy in one study. Therefore, current data suggest that zalcitabine is a useful antiretroviral agent for inclusion as a component of initial double combination therapy with zidovudine or as part of triple combination therapy including zidovudine plus a protease inhibitor in the management of patients with HIV infection.
    背景与目标: 扎西他滨是一种双脱氧核苷抗逆转录病毒药,在未感染和感染HIV的细胞中均被磷酸化为活性代谢物2',3'-二脱氧胞苷5'-三磷酸(ddCTP)。在治疗浓度下,ddCTP通过抑制酶逆转录酶并终止原病毒DNA链的延伸来抑制HIV复制。齐多夫定单一疗法与联合疗法比较的3个大型关键试验的结果现已清楚地确定,与齐多夫定单一疗法相比,齐西他滨加齐多夫定联合疗法可改善病毒载量和CD4细胞计数。最近,临床终点和替代标记数据已经确定了扎西他滨与蛋白酶抑制剂沙奎那韦联合在齐多夫定患者中的疗效。其他研究表明扎西他滨与利托那韦和核苷类似物拉米夫定联合使用。重要的是,在治疗顺序中早期使用扎西他滨似乎没有限制后续用其他核苷类似物如拉米夫定进行治疗的疗效。周围神经病变是与扎西他滨治疗相关的最常见的剂量限制性不良反应,通常在停药后可逆。扎西他滨治疗可能会经常发生口腔炎和口腔溃疡,但继续治疗后往往会缓解。扎西他滨很少报道血液毒性,这是与齐多夫定有关的常见不良反应。总的来说,与齐多夫定单一疗法相比,齐多夫定+齐多夫定或沙奎那韦联合治疗的耐受性与单独使用任一种药物相当,尽管与齐多夫定单一疗法相比,齐多夫定+齐西他滨治疗的血液学毒性发生率显着增加。学习。因此,目前的数据表明,扎西他滨是一种有用的抗逆转录病毒药物,可作为包含齐多夫定的初始双重联合疗法的组成部分或包含齐多夫定加蛋白酶抑制剂在内的三重联合疗法的一部分用于治疗HIV感染患者。
  • 【HIV-1血清流行的北印度人中TIM-1外显子4单倍型和CD4 T细胞计数的状态。】 复制标题 收藏 收藏
    DOI:10.1016/j.humimm.2012.11.013 复制DOI
    作者列表:Sharma G,Ohtani H,Kaur G,Naruse TK,Sharma SK,Vajpayee M,Kimura A,Mehra N
    BACKGROUND & AIMS: :The TIM (T cell/transmembrane, immunoglobulin and mucin) proteins are crucial regulators of Th1/Th2 immune responses and have been implicated in several diseases including HIV-1/AIDS. The TIM1 exon 4 that codes for mucin domain is highly diverse, with sequence variants associated with varying phenotypes. In this study, TIM1 exon 4 was sequenced among 227 HIV-1 seroprevalent and 288 healthy non infected individuals from North Indian population and haplotypes established. A novel but rare haplotype D1(∗) was identified among the healthy and differed from D1 by a synonymous substitution G>T at Thr208Thr. The TIM1 haplotype diversity showed no association with susceptibility to HIV-1 infection. The seroprevalent individuals carrying D3A had relatively higher median CD4+T cell counts (368/μl) than those without (313/μl; p=0.02). A comparison of CD4+T counts between D3-A individuals on ART or ART naïve did not show any significant difference plausibly due to confounding nature of ART and other factors.
    背景与目标: TIM(T细胞/跨膜,免疫球蛋白和粘蛋白)蛋白是Th1 / Th2免疫反应的关键调节剂,并与包括HIV-1 / AIDS在内的多种疾病有关。编码粘蛋白结构域的TIM1外显子4高度多样化,具有与不同表型相关的序列变体。在这项研究中,TIM1外显子4在来自北印度人口的227个HIV-1血清流行和288个健康的未感染个体中进行了测序,并建立了单倍型。在健康人群中鉴定出一种新颖但罕见的单倍型D1(∗),与D1的区别在于在Thr208Thr处的同义替代G> T。 TIM1单倍型多样性表明与HIV-1感染的易感性无关。携带D3A的血清流行个体的CD4 T细胞计数中位数相对较高(不含313 /μl; p = 0.02)。由于ART和其他因素的混杂,D3-A个体或未接受过ART的D3-A个体之间CD4 T计数的比较似乎没有显示任何显着差异。
  • 【HIV持久性:潜伏储库中细胞的克隆扩增。】 复制标题 收藏 收藏
    DOI:10.1172/JCI95329 复制DOI
    作者列表:Kwon KJ,Siliciano RF
    BACKGROUND & AIMS: :While antiretroviral therapy (ART) can reduce HIV-1 to undetectable levels, the virus generally reappears if treatment is stopped. Resurgence of the virus is due to the reactivation of T cells harboring latent integrated provirus, and recent studies indicate that proliferation of these latently infected cells helps maintain the HIV-1 reservoir. In this issue of the JCI, Lee et al. evaluated CD4+ T cell subsets to determine whether certain populations are more likely to harbor full-length, replication-competent provirus. The authors identified an enrichment of clonally expanded Th1 cells containing intact HIV-1 proviruses, suggesting that this polarized subset contributes to the persistence of the reservoir. Strategies to target these provirus-harboring cells need to be considered for future therapies aimed toward HIV-1 cure.
    背景与目标: :尽管抗逆转录病毒疗法(ART)可以将HIV-1降至无法检测的水平,但是如果停止治疗,病毒通常会重新出现。病毒的复发归因于带有潜伏性整合前病毒的T细胞的重新活化,最近的研究表明,这些潜伏感染的细胞的增殖有助于维持HIV-1的储存。在本期JCI中,Lee等人。评估了CD4 T细胞亚群,以确定某些人群是否更有可能携带全长,具有复制能力的原病毒。作者确定了含有完整HIV-1前病毒的克隆扩增Th1细胞的富集,表明该极化的子集有助于水库的持久性。在未来针对HIV-1的治疗中,需要考虑针对这些携带前病毒的细胞的策略。
  • 【睡眠障碍和相关危险因素的负担:中国艾滋病毒感染者抗逆转录病毒疗法的横断面调查。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-017-03968-3 复制DOI
    作者列表:Huang X,Li H,Meyers K,Xia W,Meng Z,Li C,Bai J,He S,Cai W,Huang C,Liu S,Wang H,Ling X,Ma P,Tan D,Wang F,Ruan L,Zhao H,Wei H,Liu Y,Yu J,Lu H,Wang M,Zhang T,Chen H,Wu H
    BACKGROUND & AIMS: :This study evaluated the prevalence and factors associated with sleep disturbance in a large cohort of HIV-infected patients across China. A cross-sectional study was conducted among HIV-infected patients on antiretroviral therapy at 20 AIDS clinics. The Pittsburgh Sleep Quality Index was self-administered by subjects. Socio-demographic characteristics, medical history and HIV-related clinical data were collected. 4103 patients had complete data for analysis. Sleep disturbances were observed in 43.1% of patients. Associated factors in multivariable analysis included psychological factors: anxiety (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.44-4.00; P < 0.001), depression (OR, 2.09; 95% CI, 1.70-2.57; P < 0.001), and both anxiety and depression (OR, 5.90; 95% CI, 4.86-7.16; P < 0.001); sociodemographic factors: MSM (OR, 1.26; 95% CI, 1.04-1.52; P = 0.018), being single (OR, 1.45; 95%CI 1.21-1.74; P < 0.001), higher education (OR, 1.25; 95% CI, 1.03-1.53; P = 0.025); and clinical factors: suboptimal adherence (OR,1.51; 95% CI,1.23-1.85; P < 0.001), regimen-switching (OR, 1.94; 95% CI, 1.12-3.35; P = 0.018), and antidepressant use (OR, 1.98; 95% CI, 1.47-2.67; P = 0.044). Prevalence of sleep disturbance is high in this large Chinese cohort. Associated factors appear related to psychological and social-demographic factors. Health workers may consider routinely assessing sleep disturbances among HIV-infected patients, especially in the first three months after HIV diagnosis, and referring for mental health services, which may positively impact adherence to treatment.
    背景与目标: :这项研究评估了中国一大批感染HIV的患者的患病率和与睡眠障碍相关的因素。在20个艾滋病诊所中,对接受HIV感染的患者进行了抗逆转录病毒治疗的横断面研究。匹兹堡睡眠质量指数由受试者自行管理。收集了社会人口统计学特征,病史和与艾滋病相关的临床数据。 4103例患者有完整的数据需要分析。在43.1%的患者中观察到睡眠障碍。多变量分析中的相关因素包括心理因素:焦虑(赔率[OR],3.13; 95%置信区间[CI],2.44-4.00; P <0.001),抑郁(OR,2.09; 95%CI,1.70-2.57;病历)。 (P <0.001),以及焦虑和抑郁(OR,5.90; 95%CI,4.86-7.16; P <0.001)。社会人口统计学因素:MSM(OR,1.26; 95%CI,1.04-1.52; P = 0.018),单身(OR,1.45; 95%CI 1.21-1.74; P <0.001),高等教育程度(OR,1.25; 95%CI,1.03-1.53​​; P = 0.025);临床因素:次最佳依从性(OR,1.51; 95%CI,1.23-1.85; P <0.001),方案转换(OR,1.94; 95%CI,1.12-3.35; P = 0.018),和抗抑郁药的使用(OR ,1.98; 95%CI,1.47-2.67; P = 0.044)。在这个庞大的中国人群中,睡眠障碍的患病率很高。相关因素似乎与心理和社会人口统计学因素有关。卫生工作者可以考虑常规评估艾滋病毒感染患者的睡眠障碍,尤其是在艾滋病毒确诊后的前三个月,并寻求心理健康服务,这可能会对治疗依从性产生积极影响。
  • 【定性研究:俄罗斯注射毒品人群获得艾滋病治疗的系统性障碍。】 复制标题 收藏 收藏
    DOI:10.1093/heapol/czs107 复制DOI
    作者列表:Sarang A,Rhodes T,Sheon N
    BACKGROUND & AIMS: :Achieving 'universal access' to antiretroviral HIV treatment (ART) in lower income and transitional settings is a global target. Yet, access to ART is shaped by local social condition and is by no means universal. Qualitative studies are ideally suited to describing how access to ART is socially situated. We explored systemic barriers to accessing ART among people who inject drugs (PWID) in a Russian city (Ekaterinburg) with a large burden of HIV treatment demand. We undertook 42 in-depth qualitative interviews with people living with HIV with current or recent experience of injecting drug use. Accounts were analysed thematically, and supplemented here with an illustrative case study. Three core themes were identified: 'labyrinthine bureaucracy' governing access to ART; a 'system Catch 22' created by an expectation that access to ART was conditional upon treated drug use in a setting of limited drug treatment opportunity; and 'system verticalization', where a lack of integration across HIV, tuberculosis (TB) and drug treatment compromised access to ART. Taken together, we find that systemic factors play a key role in shaping access to ART with the potential adverse effects of reproducing treatment initiation delay and disengagement from treatment. We argue that meso-level systemic factors affecting access to ART for PWID interact with wider macro-level structural forces, including those related to drug treatment policy and the social marginalization of PWID. We note the urgent need for systemic and structural changes to improve access to ART for PWID in this setting, including to simplify bureaucratic procedures, foster integrated HIV, TB and drug treatment services, and advocate for drug treatment policy reform.
    背景与目标: :在较低的收入和过渡环境中实现对抗逆转录病毒HIV治疗(ART)的“普遍获得”是全球目标。然而,获得抗逆转录病毒药物的途径取决于当地的社会状况,绝不是普遍的。定性研究非常适合描述获得抗逆转录病毒疗法在社会上的位置。我们探索了在俄罗斯城市(叶卡捷琳堡)注射艾滋病毒(HIV)需求量很大的注射毒品者(PWID)中获取ART的系统性障碍。我们对具有当前或最近注射吸毒经验的艾滋病毒感染者进行了42次深入的定性访谈。对帐目进行了主题分析,并在此处补充了说明性的案例研究。确定了三个核心主题:控制获取抗逆转录病毒药物的“迷宫式官僚主义”;期望在有限的药物治疗机会的情况下获得抗病毒药物的条件是要获得抗逆转录病毒药物而创建的“系统捕​​获22”;以及“系统垂直化”,即艾滋病毒,结核病和药物治疗之间缺乏整合,影响了抗逆转录病毒疗法的获取。综上所述,我们发现系统性因素在影响获得ART的过程中起着关键作用,并具有再生治疗起始延迟和脱离治疗的潜在不利影响。我们认为影响PWID获得抗逆转录病毒疗法的中观系统性因素与更广泛的宏观结构性因素相互作用,包括那些与毒品治疗政策和PWID的社会边缘化有关的因素。我们注意到迫切需要进行系统和结构上的改革,以改善在这种情况下PWID获得抗病毒治疗的途径,包括简化官僚程序,促进艾滋病毒,结核病和药物治疗的综合服务,以及倡导药物治疗政策的改革。
  • 【生命体征:美国青少年中的HIV感染,检测和危险行为。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Centers for Disease Control and Prevention (CDC).
    BACKGROUND & AIMS: BACKGROUND:In 2009, 6.7% of the estimated 1.1 million persons living with human immunodeficiency virus (HIV) infection in the United States were youths (defined in this report as persons aged 13-24 years); more than half of youths with HIV (59.5%) were unaware of their infection. METHODS:CDC used National HIV Surveillance System data to estimate, among youths, prevalence rates of diagnosed HIV infection in 2009 and the number of new infections (incidence) in 2010. To assess the prevalence of risk factors and HIV testing among youths, CDC used the 2009 and 2011 Youth Risk Behavior Surveillance System for 9th-12th grade students and the 2010 National Health Interview Survey (NHIS) for persons 18-24 years. RESULTS:Prevalence of diagnosed HIV was 69.5 per 100,000 youths at the end of 2009. Youths accounted for 12,200 (25.7%) new HIV infections in 2010. Of these, 7,000 (57.4%) were among blacks/African Americans, 2,390 (19.6%) among Hispanics/Latinos, and 2,380 (19.5%) among whites; 8,800 (72.1%) were attributed to male-to-male sexual contact. The percentage of youths tested for HIV overall was 12.9% among high school students and 34.5% among those aged 18-24 years; it was lower among males than females, and lower among whites and Hispanics/Latinos than blacks/African Americans. CONCLUSIONS:A disproportionate number of new HIV infections occurs among youths, especially blacks/African Americans, Hispanics/Latinos, and men who have sex with men (MSM). The percentage of youths tested for HIV, however, was low, particularly among males. Implications for Public Health: More effort is needed to provide effective school- and community-based interventions to ensure all youths, particularly MSM, have the knowledge, skills, resources, and support necessary to avoid HIV infection. Health-care providers and public health agencies should ensure that youths are tested for HIV and have access to sexual health services, and that HIV-positive youths receive ongoing health-care and prevention services.
    背景与目标: 背景:2009年,在美国估计有110万人患有人类免疫缺陷病毒(HIV)感染的人口中,有6.7%是青年(本报告中定义为13至24岁的人);一半以上的艾滋病毒青年(59.5%)没有意识到自己的感染。
    方法:疾病预防控制中心使用国家艾滋病毒监测系统的数据来估计年轻人中2009年确诊的艾滋病毒感染率和2010年的新感染人数(发病率)。为评估青少年中危险因素和艾滋病毒检测的患病率,疾病预防控制中心针对9至12年级学生的2009年和2011年青少年风险行为监控系统,以及针对18至24岁人群的2010年全国健康访问调查(NHIS)。
    结果:2009年底,诊断出的艾滋病毒患病率为每10万名青年中69.5名。2010年,青年新感染艾滋病毒的人数为12,200(25.7%)。其中,黑人/非裔美国人中有7,000(57.4%),2,390(19.6%)。 )在西班牙裔/拉丁裔中,白人中有2,380名(19.5%); 8,800(72.1%)来自男女之间的性接触。在高中生中,接受艾滋病毒检测的年轻人总体百分比为12.9%,在18-24岁年龄段的年轻人中为34.5%;男性比女性低,而白人和西班牙裔/拉丁美洲人比黑人/非裔美国人低。
    结论:年轻人中,尤其是黑人/非裔美国人,西班牙裔/拉丁裔和与男性发生性关系的男性中,新感染艾滋病毒的比例不成比例。但是,接受艾滋病毒检测的年轻人比例很低,尤其是在男性当中。对公共卫生的影响:需要付出更多的努力来提供有效的基于学校和社区的干预措施,以确保所有青年,尤其是男男性接触者,拥有避免感染艾滋病毒所需的知识,技能,资源和支持。卫生保健提供者和公共卫生机构应确保对青年进行艾滋病毒检测并获得性保健服务,并确保艾滋病毒呈阳性的青年得到持续的卫生保健和预防服务。
  • 【实验性基因治疗:在重症合并免疫缺陷小鼠中,Tat诱导型干扰素基因的转移可在体外和体内保护人体细胞免受HIV-1攻击。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:1997-07-01
    来源期刊:AIDS
    DOI:10.1097/00002030-199708000-00005 复制DOI
    作者列表:Sanhadji K,Leissner P,Firouzi R,Pelloquin F,Kehrli L,Marigliano M,Calenda V,Ottmann M,Tardy JC,Mehtali M,Touraine JL
    BACKGROUND & AIMS: OBJECTIVES:To evaluate in vitro and in vivo a strategy for gene therapy for AIDS based on the transfer on interferon (IFN)-alpha, -beta and -gamma genes to human cells.

    DESIGN:Human U937 promonocytic cells were stably transfected with Tat-inducible IFN expression vectors conferring an antiviral state against infection with HIV.

    METHODS:Transfected cells were either infected by HIV-1 in vitro or transplanted into severe combined immunodeficient (SCID) mice for an HIV challenge in vivo.

    RESULTS:U937 cell lines stably carrying IFN transgenes under the positive control of the HIV-1 Tat protein were highly resistant to HIV-1 replication in vitro. This antiviral resistance was associated with a strong induction of IFN synthesis immediately following the viral infection. HIV-1 proteins were found to be specifically trapped within the genetically modified cells. In contrast, all IFN-U937 cells permitted full HIV-2 replication. Transfected cells injected into SCID mice and challenged against HIV-1 were strongly resistant to infection when cells were transduced with IFN-alpha of IFN-beta genes. However, IFN-gamma-transfected cells permitted HIV-1 infection in vivo despite the induction of a high level of IFN-gamma secretion. The quantity of proviral DNA was 10(5)-fold lower in IFN-alpha- or IFN-beta-transfected U937 cells collected from these SCID mice than that in non-transfected cells.

    CONCLUSIONS:Our results substantiated the validity of a strategy, bases on the transfer of HIV-1-inducible IFN-alpha or IFN-beta genes, to confer antiviral resistance to human cells.

    背景与目标: 目标:基于干扰素(IFN)-α,-β和-γ基因向人体细胞的转移,评估体内和体外的AIDS基因治疗策略。

    DESIGN :人类T937前单核细胞被Tat诱导型IFN表达载体稳定转染,可赋予抗HIV感染的抗病毒状态。

    方法:转染的细胞可以被HIV-1体外感染,也可以被移植到严重的联合免疫缺陷(SCID)小鼠体内进行HIV攻击。

    结果:在该条件下稳定携带IFN转基因的U937细胞系HIV-1 Tat蛋白的阳性对照在体外对HIV-1复制具有高度抗性。这种抗病毒耐药性与病毒感染后立即强烈诱导IFN合成有关。发现HIV-1蛋白被特异地捕获在转基因细胞中。相比之下,所有IFN-U937细胞都允许HIV-2完全复制。当用IFN-β基因的IFN-α转导细胞时,注入SCID小鼠并受到HIV-1攻击的转染细胞对感染具有强烈的抵抗力。然而,尽管诱导了高水平的IFN-γ分泌,但是IFN-γ转染的细胞仍允许体内HIV-1感染。从这些SCID小鼠收集的IFN-α-或IFN-β转染的U937细胞中,原病毒DNA的数量比未转染的细胞低10(5)倍。

    结论< / strong>:我们的研究结果证实了基于HIV-1诱导型IFN-α或IFN-β基因转移的策略的有效性,以赋予人类细胞抗病毒抗性。

  • 【靶向gp41 N和C端七肽重复序列的抑制剂对HIV-1包膜介导的膜融合的协同抑制作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.jmb.2006.09.017 复制DOI
    作者列表:Gustchina E,Louis JM,Bewley CA,Clore GM
    BACKGROUND & AIMS: :The human immunodeficiency virus type-1 (HIV-1) envelope (Env) proteins that mediate membrane fusion represent a major target for the development of new AIDS therapies. Three classes of Env-mediated membrane fusion inhibitors have been described that specifically target the pre-hairpin intermediate conformation of gp41. Class 2 inhibitors bind to the C-terminal heptad repeat (C-HR) of gp41. The single example of a class 3 inhibitor targets the trimeric N-terminal heptad repeat (N-HR) of gp41 and has been postulated to sequestrate the N-HR of the pre-hairpin intermediate through the formation of fusion incompetent heterotrimers. Here, we show that N(CCG)-gp41, a class 2 inhibitor, and N36(Mut(e,g)), a class 3 inhibitor, synergistically inhibit Env-mediated membrane fusion for several representative HIV-1 strains (X4 and R5) in both a cell fusion assay (with membrane-bound CD4) and an Env-pseudo-typed virus neutralization assay. The mechanistic, as well as potential therapeutic, implications of these observations for HIV-Env-mediated membrane fusion are discussed.
    背景与目标: :介导膜融合的人类1型免疫缺陷病毒(HIV-1)包膜(Env)蛋白代表了开发新的AIDS疗法的主要目标。已经描述了三类Env介导的膜融合抑制剂,它们专门针对gp41的发夹前中间体构象。 2类抑制剂与gp41的C端七肽重复序列(C-HR)结合。第3类抑制剂的单个实例靶向gp41的三聚体N端七末端重复序列(N-HR),并已假定通过形成不适合的融合三聚体来隔离发夹前中间体的N-HR。在这里,我们显示N(CCG)-gp41(一种2类抑制剂)和N36(Mut(e,g))(一种3类抑制剂)协同抑制Env介导的几种代表性HIV-1菌株的膜融合(X4和R5)在细胞融合测定(带有膜结合CD4)和Env-伪型病毒中和测定中都可以使用。讨论了这些观察结果对HIV-Env介导的膜融合的机理以及潜在的治疗意义。
  • 【HIV 1型感染对象的血液中的细胞毒性单核细胞以CD95依赖性方式破坏靶向的T细胞。】 复制标题 收藏 收藏
    DOI:10.1089/aid.1997.13.953 复制DOI
    作者列表:Orlikowsky T,Wang ZQ,Dudhane A,Horowitz H,Riethmuller G,Hoffmann MK
    BACKGROUND & AIMS: HIV-1 infection changes the functional balance of macrophages in the body; it inhibits the development of macrophages capable of costimulating T cell responses and it favors the development of macrophages that kill T cells with which they form cellular conjugates. Cytotoxic macrophages destroy CD4 T cells, which they target through CD4-reactive immune-complexed HIV-1 envelope molecules on a large scale. They also destroy T cells that they target through presented antigen or mitogen. We show here that cytotoxic macrophages destroy their cellular targets at least partially in a CD95-dependent process in which T cells first modulate expression of most of their membrane receptors and subsequently die.

    背景与目标: HIV-1感染会改变体内巨噬细胞的功能平衡;它抑制能够协同刺激T细胞反应的巨噬细胞的发育,并且有利于杀死与细胞形成细胞结合物的T细胞的巨噬细胞的发育。细胞毒性巨噬细胞破坏CD4 T细胞,它们通过CD4反应性免疫复合HIV-1包膜分子大规模靶向。它们还破坏了通过呈递的抗原或有丝分裂原靶向的T细胞。我们在这里表明,细胞毒性巨噬细胞在CD95依赖性过程中至少部分破坏其细胞靶标,在该过程中,T细胞首先调节大多数膜受体的表达,然后死亡。

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