HIV-1 Incidence and Genetic Diversity in the Caribbean

加勒比地区的 HIV-1 发病率和遗传多样性

• 批准号: 6765843
• 负责人: WILLIAM Albert BLATTNER
• 金额: $ 20.49万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6765843
• 关键词: Caribbean; Caribbean islands; HIV infections; Puerto Rico; bioassay; clinical research; communicable disease transmission; computer program /software; drug resistance; epidemiology; genetic recombination; human immunodeficiency virus 1; human subject; polymerase chain reaction; virus genetics; western blottings

DESCRIPTION (provided by applicant): Two distinct but highly related research projects will be conducted to accurately determine HIV incidence and HIV molecular diversity/recombination in populations at high risk of HIV infection in five Caribbean countries (Jamaica, Trinidad, Haiti, the Dominican Republic and Puerto Rico) participating in the HIV Vaccine Trials Network (HVTN). The data generated by these studies will be critical to implementation of Phase III vaccine trials. The hypotheses to be tested are 1) that recent high HIV-1 incidence can be conveniently and reliably estimated using a modified sensitive/less sensitive (S/LS) assay on archived crosssectionally collected samples from high-risk populations, and 2) that the predominant circulating HIV subtype is clade B, with little or no evidence of recombination in the RT/protease region of the pol gene, which is the most frequent site for recombination. In addition, the data generated will provide information about common anti-retroviral resistance mutations in incident (circulating) HIV that we predict will be absent in these largely treatment naive populations. The PI, a senior scientist at the IHV/UMD, is highly experienced in conducting collaborative epidemiologic/virologic studies in the region, and will collaborate with experts in HIV molecular characterization at the Henry Jackson Foundation, as well as clinical HVTN investigators in the Caribbean. These two related projects will utilize existing characterized serum/plasma collections that will be assayed with the S/LS assay at IHV, which is a participating laboratory in the IND held by CDC, to provide incidence data. Using a two-stage algorithm to accurately characterize the incident samples, at least 50 incident samples (10 per site) will then be sequenced in the RT/protease region of the genome that commonly includes recombination breakpoints. This rapid assessment will then be confirmed using a newly developed technique in a subset of 25/50 (5 per site) full-length genomes that will be sequenced from viral RNA extracted from serum. Data generated by these studies will validate the rationale for including these five sites in vaccine and prevention testing networks and help to bolster the evidence base for programs to control the spread of HIV. Innovation is presented in the use of a modified S/LS assay algorithm to rapidly ascertain incidence estimates and accurately identify incident samples, and in the use of overlapping RT PCR for full genome sequencing of viral RNA from incident serum (cell-free) samples.

描述（由申请人提供）：将进行两个不同但高度相关的研究项目，以准确确定参与艾滋病毒疫苗试验网络（HVTN）的五个加勒比国家（牙买加、特立尼达、海地、多米尼加共和国和波多黎各）艾滋病毒感染高风险人群中的艾滋病毒发病率和艾滋病毒分子多样性/重组。这些研究产生的数据将对实施三期疫苗试验至关重要。需要验证的假设是：1)近期的HIV-1高发病率可以使用改进的敏感/低敏感（S/LS）方法方便可靠地估计来自高危人群的横断面收集的样本，2)主要的循环HIV亚型是进化支B，在pol基因的RT/蛋白酶区域很少或没有重组的证据，这是最常见的重组位点。此外，所产生的数据将提供关于偶发（循环）艾滋病毒中常见的抗逆转录病毒耐药性突变的信息，我们预测这些突变在这些大量未接受治疗的人群中是不存在的。PI是国际艾滋病毒/艾滋病研究所的资深科学家，在该区域开展流行病学/病毒学合作研究方面经验丰富，并将与Henry Jackson基金会的艾滋病毒分子特征专家以及加勒比地区的临床HVTN调查人员合作。这两个相关的项目将利用现有的特征血清/血浆收集，这些收集将在IHV进行S/LS测定，IHV是疾病预防控制中心持有的IND的参与实验室，以提供发病率数据。使用两阶段算法来准确表征事件样本，然后在基因组的RT/蛋白酶区域（通常包括重组断点）对至少50个事件样本（每个位点10个）进行测序。这种快速评估将使用一种新开发的技术在25/50（每个位点5个）全长基因组的子集中得到证实，这些基因组将从从血清中提取的病毒RNA中测序。这些研究产生的数据将验证将这五个地点纳入疫苗和预防测试网络的基本原理，并有助于加强控制艾滋病毒传播规划的证据基础。创新之处在于使用改进的S/LS分析算法来快速确定发病率估计并准确识别事件样本，并使用重叠RT - PCR对事件血清（无细胞）样本的病毒RNA进行全基因组测序。