WOMEN'S HEALTH AGENDA

女性健康议程

• 批准号: 6099236
• 负责人: ROBERT J FASS
• 金额: $ 18.84万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6099236
• 关键词: 2'3' dideoxyinosine; AIDS; AIDS therapy; HIV infections; antiAIDS agent; biomarker; candidiasis; cervix neoplasms; clinical research; clinical trial phase I; comorbidity; cooperative study; drug screening /evaluation; female; human immunodeficiency virus 1; human pregnant subject; human subject; human therapy evaluation; immunotherapy; mucosal immunity; opportunistic infections; pharmacokinetics; reproductive system disorder; women's health

Because most adults harbor latent herpes simplex (HSV), HSV infections are common opportunistic pathogens of individuals with acquired immunodeficiency syndrome (AIDS). Recent studies have demonstrated that HSV can also infect the same type of cells infected by human immunodeficiency virus (HIV-1) and furthermore studies using chimeric constructs have demonstrated that HSV can transactivate the long terminal repeat of HIV. While these results suggest that there may be potential interactions between HIV and HSV that are important to the development of AIDS, most of these studies are based upon molecular and immunological data from in vitro studies. Clinical studies on the interactions between these viruses have been based upon serological data and the evaluation of this data has been difficult because of the high incidence of seropositivity for HSV among HIV-1 infective individuals. Furthermore, these studies have not provided any data concerning the mechanism by which HSV may interact with HIV. A possible problem with these clinical studies is that they have focused on determining the levels of antibodies that react with structural proteins of HSV. In this study we plan to do a retrospective study to determine the level of antibodies against proteins, some of which are required for HSV replication, that are expressed early in HSV infections (DNA polymerase, DNase and the 65K DNA binding protein and to correlate the pattern of antibody expression with the clinical course of HIV infection. We also plan to do a prospective study in which we follow the same antibody patterns, isolate HSV from infected individuals and determine the level of resistance of these isolates to the antiviral agents used for chemotherapy in AIDS patients. Furthermore, using polymerase chain reaction and DNA sequencing techniques, we will determine the mutations which accumulate in the HSV DNA polymerase and thymidine kinase genes as a function of time treatment and the antiviral agent used and correlate these data with clinical manifestations of the disease. The significance of this study is that it will provide new methods for predicting the onset of active HSV infections as well as the emergence of drug resistant mutants of HSV so that prophylactic treatment can be administered. Such early intervention may prove to be more effective in limiting the morbidity of the disease.

由于大多数成年人都有潜在的疱疹（HSV），因此HSV感染是 获得的个体的常见机会病原体 免疫缺陷综合征（AIDS）。最近的研究表明HSV 还可以感染受人免疫缺陷感染的相同类型的细胞 病毒（HIV-1），以及使用嵌合构建体的研究 证明HSV可以反式激活HIV的长时间重复。 尽管这些结果表明可能存在潜在的相互作用 在艾滋病毒和HSV之间对艾滋病的发展很重要，大多数 这些研究基于体外的分子和免疫学数据 研究。 关于这些病毒之间相互作用的临床研究 基于血清学数据，对该数据的评估是 由于HSV的血清阳性发生率很高，因此很难 HIV-1感染性个体。 此外，这些研究尚未提供 有关HSV可能与HIV相互作用的机制的任何数据。 一个 这些临床研究可能的问题是，他们专注于 确定与结构蛋白反应的抗体水平 HSV。 在这项研究中，我们计划进行回顾性研究，以确定 针对蛋白质的抗体水平，其中一些是HSV 复制，在HSV感染早期表达（DNA聚合酶， DNase和65K DNA结合蛋白，并将 HIV感染的临床过程，抗体表达。 我们也是 计划进行一项前瞻性研究，我们遵循相同的抗体 模式，来自感染个体的孤立性HSV，并确定 这些分离株对用于化学疗法的抗病毒剂的抗性 在艾滋病患者中。 此外，使用聚合酶链反应和DNA 测序技术，我们将确定积累的突变 HSV DNA聚合酶和胸苷激酶基因随时间的函数 治疗和使用并将这些数据与抗病毒剂与 该疾病的临床表现。 这项研究的意义是 它将提供预测活动HSV发作的新方法 HSV的感染以及耐药突变体的出现 可以给予预防性治疗。 这样的早期干预 可能被证明在限制疾病的发病率方面更有效。