HSV INFECTION IN HIV INFECTED INDIVIDUALS

HIV 感染者中的 HSV 感染

• 批准号: 6099493
• 负责人: Lawrence Corey
• 金额: $ 16.63万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6099493
• 关键词: AIDS therapy; HIV infections; acyclovir; antiviral agents; clinical research; combination chemotherapy; communicable disease transmission; disease /disorder proneness /risk; genital herpes; genital secretion; herpes simplex virus 2; homosexuals; human immunodeficiency virus 1; human subject; human therapy evaluation; microorganism culture; microorganism disease chemotherapy; opportunistic infections; polymerase chain reaction; virion; virus DNA; virus RNA; virus load; virus replication; virus virus interaction

Almost all HIV infected persons are infected with herpes simplex viruses (HSV). From 40-95% of HIV positive persons are HSV-2 seropositive. Within the last funding period our studies have indicated that among men who have sex with men, prior HSV-2 infection, infection significantly increases the likelihood of acquiring HIV-1 (R.R. 1.7, P=.04). Conversely, among HIV and HSV-2 co-infected persons, high titers of HIV-1 RNA are found in almost all genital lesions for a prolonged duration, suggesting HSV-2 may play an important role in increasing the efficiency of transmission of HIV-1. In addition, frequent subclinical HSV-2 reactivation may be a significant co- factor in initiating bursts of HIV-1 replication in genitourinary compartments and the total HIV-1 viral load. Our proposed studies are centered upon answering these issues. They include: 1) Collaborating with NIAID supported HIVNET to evaluate whether prior HSV-2 infection increases the risk of HIV-1 acquisition in women; 2) Conducting a series of studies to evaluate in subclinical HSV shedding causes HIV-1 replication in semen, cervicovaginal and rectal mucosa; 3) evaluating if antiviral therapy for HSV can suppress HIV replication in genital lesions; 4) Determining if chronic daily acyclovir therapy reduces plasma virus load. HSV infection also affords a unique opportunity for evaluating whether highly active anti-retroviral therapy (HAART) effectively influences host immune control of an opportunistic pathogen. Proposed studies evaluate the frequency of HSV reactivation by quantitative PCR prior to, 4 months after, and 12 months after initiation of HAART in HIV+ persons with high and lower CD4 T cell counts. The above studies will define what management strategies can reduce the morbidity of HSV infection on HIV progression. They will also provide important information on the potential role HSV has in the spread of sexually transmitted and sexually acquired HIV and define potential intervention strategies for interrupting such transmission.

几乎所有受艾滋病毒感染的人都感染了单纯疱疹病毒 （HSV）。从40-95％的艾滋病毒阳性人群是HSV-2血清阳性。之内 我们的研究的最后一个资金期间表明，有 与男性的性别，先前的HSV-2感染，感染显着增加 获取HIV-1的可能性（R.R. 1.7，p = .04）。相反，在艾滋病毒和 HSV-2共感染的人，在几乎发现HIV-1 RNA的高滴度 所有生殖器病变延长持续时间，表明HSV-2可能会发挥 在提高HIV-1传播效率方面的重要作用。在 此外，频繁的亚临床HSV-2重新激活可能是显着的共同 启动HIV-1复制爆发的因素 隔室和HIV-1病毒负荷。我们提出的研究是 以回答这些问题为中心。它们包括：1）与 NIAID支持Hivnet评估先前的HSV-2感染是否增加 女性HIV-1获取的风险； 2）进行一系列研究 为了评估亚临床HSV脱落会导致精液中的HIV-1复制， 宫颈阴道和直肠粘膜； 3）评估抗病毒疗法是否用于 HSV可以抑制生殖器病变中的HIV复制； 4）确定是否 慢性每日阿昔洛韦治疗可减少血浆病毒负荷。 HSV感染还为评估是否是否 高度活跃的抗逆转录病毒疗法（HAART）有效地影响宿主 机会性病原体的免疫控制。提出的研究评估了 在4个月之前定量PCR的HSV重新激活频率 之后，在HAART启动HIV+的人中12个月之后 和较低的CD4 T细胞计数。 以上研究将定义哪些管理策略可以减少 HSV感染对HIV进展的发病率。他们还将提供 HSV在传播中的潜在作用的重要信息 性传播和性获得的艾滋病毒并定义潜力 干预策略中断这种传播。