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)将广泛应用于HIV-1感染者。 Cells/ul。我们假设：1.发起艺术的一小部分秘鲁成年人会有不和谐的 抑制血液和生殖道/直肠中的病毒复制。2.病毒持续从 生殖道或直肠通常会由于病毒的产生而产生免疫激活后的潜伏感染 细胞，这将发生在不产生耐药性的情况下；然而，在某些情况下，脱落将 这是由于病毒的持续复制，这将与抗药性病毒的选择有关。 通过这些机制辨别生殖器/直肠脱落的相对频率对公众来说很重要 健康。虽然没有复制的蜕皮可能会将性伴侣置于感染的风险中，但我们怀疑 由于病毒在低病毒载量下脱落，这些脱落物的传染性将较低。相比之下，那些 与病毒复制相关的生殖器/直肠脱落病毒可能会排出更高水平的病毒，并具有 排出抗药性病毒的风险更高。后一类人会带来更高的公共健康风险， 因为由于生殖器/直肠病毒载量较高，他们更有可能传播病毒，而且更有可能 传播抗药性病毒，减少社区内抗逆转录病毒疗法的好处。通过对血液的研究 以及生殖器/直肠分泌物和活检，包括随着时间的推移，病毒载量和遗传学，这项研究旨在 测定血浆和生殖道/直肠中病毒的不协调性脱落率；测定 与不和谐脱毛相关的流行病学因素；并提供对 潜伏前病毒激活与全周期复制病毒表达的致病机制 耐药病毒的筛选。 与公共健康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。抑制血液中病毒复制的有效治疗方法不会减少 大约三分之一的接受治疗的患者的直肠和生殖道病毒脱落。通过研究病毒遗传学 我们的目标是弄清当艾滋病毒从生殖道和直肠排出的机制 在血液中被压抑。更好地了解这种不和谐的生殖道和直肠脱落应该 使我们能够制定更好的治疗战略，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.