Mechanism/predictors of genital/rectal HIV shedding during ART w/plasma <50c/mL

血浆 <50c/mL 的 ART 期间生殖器/直肠 HIV 脱落的机制/预测因素

• 批准号: 7898365
• 负责人: Lisa M Frenkel
• 金额: $ 34.59万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7898365
• 关键词: Adherence; Adult; Anal Sex; Anatomic Sites; Anti-Retroviral Agents; Antiviral Agents; Archives; Biological Assay; Biopsy; Blood; CD4 Positive T Lymphocytes; Cells; Cervical; Clinical; Communities; DNA; Detection; Development; Disease; Drug resistance; Environment; Enzyme Immunoassay; Epidemiologic Factors; Epidemiological Factors; Evolution; Failure; Frequencies; Genetic; Genital system; Genome; Goals; HIV; HIV-1; IL8 gene; Immune; Individual; Infection; Inflammation; Inflammatory; Interleukin-6; Language; Lead; Liquid Chromatography; Longitudinal Studies; Lymphocyte; Mutation; Pathogenesis; Penetration; Peru; Pharmaceutical Preparations; Pharmacotherapy; Phylogenetic Analysis; Plasma; Process; Proctitis; Production; Proviruses; Public Health; RNA; Rectum; Relative (related person); Research Personnel; Reverse Transcription; Risk; Risk Factors; Seminal Plasma; Sex Behavior; Sexual Partners; Sexual Transmission; Simplexvirus; Specimen; Testing; Time; Time Study; Tissues; Transcriptional Activation; Transudate; Trauma; Treatment Failure; Variant; Viral; Viral Load result; Virus; Virus Replication; Virus Shedding; Woman; Work; antiretroviral therapy; cytokine; drug resistant virus; effective therapy; genital secretion; high risk; insight; latent virus activation; men; mutant; non-nucleoside reverse transcriptase inhibitors; particle; peripheral blood; pill; prevent; programs; rectal; tool; transmission process; treatment strategy; virus genetics; Adherence; Adult; Anal Sex; Anatomic Sites; Anti-Retroviral Agents; Antiviral Agents; Archives; Biological Assay; Biopsy; Blood; CD4 Positive T Lymphocytes; Cells; Cervical; Clinical; Communities; DNA; Detection; Development; Disease; Drug resistance; Environment; Enzyme Immunoassay; Epidemiologic Factors; Epidemiological Factors; Evolution; Failure; Frequencies; Genetic; Genital system; Genome; Goals; HIV; HIV-1; IL8 gene; Immune; Individual; Infection; Inflammation; Inflammatory; Interleukin-6; Language; Lead; Liquid Chromatography; Longitudinal Studies; Lymphocyte; Mutation; Pathogenesis; Penetration; Peru; Pharmaceutical Preparations; Pharmacotherapy; Phylogenetic Analysis; Plasma; Process; Proctitis; Production; Proviruses; Public Health; RNA; Rectum; Relative (related person); Research Personnel; Reverse Transcription; Risk; Risk Factors; Seminal Plasma; Sex Behavior; Sexual Partners; Sexual Transmission; Simplexvirus; Specimen; Testing; Time; Time Study; Tissues; Transcriptional Activation; Transudate; Trauma; Treatment Failure; Variant; Viral; Viral Load result; Virus; Virus Replication; Virus Shedding; Woman; Work; antiretroviral therapy; cytokine; drug resistant virus; effective therapy; genital secretion; high risk; insight; latent virus activation; men; mutant; non-nucleoside reverse transcriptase inhibitors; particle; peripheral blood; pill; prevent; programs; rectal; tool; transmission process; treatment strategy; virus genetics

In Peru antiretroviral therapy (ART) will be broadly available to HIV-1 infected individuals with <250 CD4 cells/uL. We hypothesize that: 1. A subset of Peruvian adults who initiate ART will have discordant suppression of viral replication in the blood and genital tract/rectum. 2. Continued shedding of virus from the genital tract or rectum will often be due to virus production following immune activation of latently infected cells, which will occur without the development of drug resistance; however, in some instances shedding will be due to continued viral replication, which will be associated with selection of drug-resistant virus. Discerning the relative frequency of genital/rectal shedding by these mechanisms is important for public health. While shedding without replication could place sexual partners at risk of infection, we suspect the infectiousness of these shedders will be low due to shedding of virus at low viral loads. In contrast, those that shed genital/rectal virus in association with viral replication will likely shed higher levels of virus, and have a higher risk of shedding drug-resistant virus. These latter individuals would present a higher public health risk, as they would be more likely to transmit virus due to higher genital/rectal viral loads and would be more likely to transmit drug-resistant virus, diminishing the benefits of ART within the community. By studies of blood and genital/rectal secretions and biopsies, including viral loads and genetics over time, this study aims to determine the rate of discordant shedding of virus in the blood plasma and genital tract/rectal; determine the epidemiological factors associated with discordant shedding; and provide further insight into the pathogenesis of expression of virus from activation of latent provirus versus full-cycles of replication with selection of drug-resistant virus. Lay language description of relevance to public health: Viral shedding from the rectum and genital tract allows transmission of HIV. Effective treatment that suppresses viral replication in the blood, does not curtail rectal and genital tract viral shedding from about one-third of treated individuals. By studying viral genetics we aim to discern the mechanisms that allow HIV to be shed from the genital tract and rectum when suppressed in the blood. A better understanding of this discordant genital tract and rectal shedding should allow us to develop better treatment strategies that should reduce HIV transmission.

在秘鲁抗逆转录病毒疗法中（ART）将广泛用于HIV-1感染<250 CD4的个体 细胞/UL。我们假设：1。发起艺术的秘鲁成年人的子集将不和谐 血液和生殖道/直肠的病毒复制抑制。 2。继续从 生殖道或直肠通常是由于潜在感染的免疫激活后的病毒产生 细胞将在不产生耐药性的情况下发生；但是，在某些情况下会脱落 由于持续的病毒复制，这将与选择抗药性病毒有关。 通过这些机制辨别生殖器/直肠脱落的相对频率对公众很重要 健康。虽然没有复制而脱落可能会使性伴侣处于感染风险，但我们怀疑 由于在低病毒载荷下病毒脱落，这些茎的感染性将很低。相反，那些 与病毒复制相关的生殖器/直肠病毒可能会散发出更高水平的病毒，并具有A 释放耐药病毒的风险更高。这些后一个人会带来更高的公共卫生风险， 因为由于较高的生殖器/直肠病毒负荷，它们更有可能传播病毒，并且更有可能 为了传播抗药性病毒，减少了社区中艺术的好处。通过血液研究 随着时间的流逝，生殖器/直肠分泌物和活检，包括病毒载荷和遗传学，本研究的目的是 确定血浆和生殖道/直肠病毒中病毒不一致的脱落率；确定 与不一致的脱落有关的流行病学因素；并进一步了解 潜在病毒的激活与复制的全周期的激活与病毒表达的发病机理 选择耐药病毒。 与公共卫生相关性的外行语言描述：直肠和生殖道的病毒脱落 允许传播艾滋病毒。有效抑制血液中病毒复制的治疗方法不会减少 直肠和生殖道病毒脱落，大约三分之一的治疗个体。通过研究病毒遗传学 我们旨在辨别允许艾滋病毒从生殖道和直肠中脱离的机制 被抑制的血液。更好地了解这种不和谐的生殖道和直肠脱落 允许我们制定更好的治疗策略，以减少HIV传播。