Modeling Inflammation in HIV Transmission

HIV 传播中的炎症建模

• 批准号: 8842922
• 负责人: CHRISTOPHER James MILLER
• 金额: $ 101.33万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8842922
• 关键词: Affect; Animals; Anti-Inflammatory Agents; Anti-Retroviral Agents; Anti-inflammatory; Biology; Biology of HIV Transmission; Biopsy; Blood; Cells; Clinical Trials; Conduct Clinical Trials; Conflict (Psychology); DNA; Dose; Epidemiologic Studies; Epidemiology; Gel; Genital system; HIV; HIV Infections; HIV vaccine; HIV-1; Health; Heterosexuals; Human; Human Herpesvirus 2; Immune response; Immunofluorescence Immunologic; Immunohistochemistry; Immunology; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Irrigation; Macaca; Macaca mulatta; Messenger RNA; Methods; Modeling; Mucous Membrane; Nature; Pathogenesis; Pathway interactions; Pattern; Pharmaceutical Preparations; Population; Predisposition; Process; Prophylactic treatment; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Risk; Role; SIV; Sampling; Scheme; Sexually Transmitted Diseases; Swab; T-Lymphocyte; Technology; Tenofovir; Testing; Time; Tissues; Topical application; Vaccines; Vagina; Variant; Virus; Woman; antimicrobial; cervicovaginal; chemokine; cytokine; design; effective intervention; follow-up; men who have sex with men; microbicide; nonhuman primate; novel strategies; phase III trial; preclinical study; prevent; prophylactic; sexual HIV transmission; success; therapeutic vaccine; transmission process; truvada; vaccine candidate; virology

DESCRIPTION (provided by applicant): Despite the inefficiency of HIV transmission and the availability of methods to prevent HIV transmission, 2.6 million individuals acquire HIV infections every year. Although the CAPRISA Phase III trial found that tenofovir microbicide decreased HIV infection in women, the follow-up VOICE Phase III trial of the same microbicide gel failed to demonstrate any protection. Thus, in order to develop consistently effective interventions that can prevent HIV acquisition a more detailed understanding of the biology of HIV transmission populations most at risk for infection. The presence or absence of genital inflammation is of fundamental importance since and epidemiologic studies suggest that the risk of acquiring HIV-1 infection is increased in women with cervicovaginal inflammation induced by sexually transmitted infections especially HSV-2. However, despite the epidemiologic associations and supporting circumstantial evidence, it is not possible to directly determine the effects of genital inflammation on HIV transmission in humans. This project will use a non-human primate (NHP) model to provide a detailed understanding of the role of HSV2 induced genital inflammation in HIV transmission and dissemination after vaginal exposure. We have defined the target cells and dissemination pathways and the number and nature of founder SIV variants after vaginal SIVmac251 exposure. However, all these studies have been conducted with mature macaques chosen without regard to levels of pre-existing genital inflammation. Inflammation may affect critical parameters in HIV transmission and pathogenesis that, in turn can alter the ability of a vaccine or microbicide to prevent HIV transmission. These parameters include the dose of HIV required to infect an individual and the rate of HIV dissemination from the genital tract to systemic tissues. Once the virology of vaginal SIV transmission in the setting of genital inflammation is characterized, then this NHP model will be useful for testing candidate vaccines and microbicides designed to prevent HIV transmission. Moreover, in this proposal we will develop and test the hypothesis that combining antimicrobial therapy and topical anti-inflammatory agents will reduce the effect of genital inflammation on transmission.

描述（由申请人提供）：尽管艾滋病毒传播效率低下，并且有预防艾滋病毒传播的方法，但仍有260万人感染艾滋病毒