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）：将开展两个不同但高度相关的研究项目，以准确确定五个加勒比国家（牙买加、特立尼达、海地、多米尼加共和国）艾滋病毒感染高危人群的艾滋病毒发病率和艾滋病毒分子多样性/重组和波多黎各）参与艾滋病毒疫苗试验网络（HVTN）。这些研究产生的数据对于实施第三阶段疫苗试验至关重要。要测试的假设是 1) 最近的高 HIV-1 发病率可以使用改良的敏感/低敏感 (S/LS) 测定法对从高危人群中收集的横断面存档样本进行方便而可靠的估计，以及 2)主要的循环 HIV 亚型是进化枝 B，在 pol 基因的 RT/蛋白酶区域（最常见的重组位点）几乎没有或没有重组的证据。此外，生成的数据将提供有关事件（循环）艾滋病毒中常见抗逆转录病毒耐药突变的信息，我们预测这些突变在这些基本上未接受过治疗的人群中将不存在。该 PI 是 IHV/UMD 的资深科学家，在该地区开展流行病学/病毒学合作研究方面拥有丰富的经验，并将与亨利·杰克逊基金会的 HIV 分子特征专家以及加勒比地区的临床 HVTN 研究人员合作。这两个相关项目将利用现有的特征血清/血浆收集品，并在 IHV（CDC 主持的 IND 参与实验室）进行 S/LS 检测，以提供发病率数据。使用两阶段算法准确表征事件样本，然后将在通常包含重组断点的基因组 RT/蛋白酶区域对至少 50 个事件样本（每个位点 10 个）进行测序。然后，将使用新开发的技术在 25/50（每个位点 5 个）全长基因组的子集中确认这种快速评估，这些基因组将从血清中提取的病毒 RNA 进行测序。这些研究产生的数据将验证将这五个站点纳入疫苗和预防测试网络的理由，并有助于加强控制艾滋病毒传播计划的证据基础。创新之处在于使用改进的 S/LS 测定算法来快速确定发病率估计值并准确识别事件样本，以及使用重叠 RT PCR 对事件血清（无细胞）样本中的病毒 RNA 进行全基因组测序。