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

在秘鲁，抗逆转录病毒疗法（ART）将广泛提供给CD4 <250的HIV-1感染者。 细胞/uL。我们假设：1.开始ART的秘鲁成年人的一个子集将有不一致的 抑制血液和生殖道/直肠中的病毒复制。2.病毒继续从 生殖道或直肠的感染通常是由于潜伏感染者的免疫激活后产生病毒所致。 细胞，这将发生而不会产生耐药性;然而，在某些情况下，脱落将 可能是由于病毒持续复制，这将与耐药病毒的选择有关。 通过这些机制辨别生殖器/直肠脱落的相对频率对于公众来说是重要的。 健康虽然没有复制的脱落可能会使性伴侣处于感染的风险中，但我们怀疑， 由于在低病毒载量下病毒的脱落，这些脱落者的感染性将是低的。相反，那些 与病毒复制相关的生殖器/直肠病毒的排出可能会排出更高水平的病毒， 更高的传播耐药病毒的风险。后一种人会带来更高的公共卫生风险， 因为他们更有可能传播病毒，因为生殖器/直肠病毒载量更高， 传播耐药病毒，减少了社区内ART的益处。通过血液研究 生殖器/直肠分泌物和活检，包括病毒载量和遗传学随着时间的推移，这项研究的目的是 确定血浆和生殖道/直肠中病毒的不一致脱落率; 与不一致脱落相关的流行病学因素;并提供对 从潜伏前病毒的激活与复制的全周期的病毒表达的发病机制 耐药病毒的筛选。 与公共卫生相关的通俗语言描述：直肠和生殖道的病毒脱落 允许艾滋病毒的传播。有效的治疗，抑制病毒在血液中的复制，不削减 直肠和生殖道病毒脱落从约三分之一的治疗个体。通过研究病毒遗传学 我们的目标是辨别艾滋病病毒从生殖道和直肠传播的机制， 被抑制在血液中。更好地了解这种不和谐的生殖道和直肠脱落， 使我们能够制定更好的治疗策略，减少艾滋病毒的传播。

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.