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: 6696111
• 负责人: Farley R Cleghorn
• 金额: $ 21.7万
• 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 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6696111
• 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HIV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）中HIV感染高危人群的HIV发病率和HIV分子多样性/重组。这些研究所产生的数据对于III期疫苗试验的实施至关重要。待检验的假设是：1）使用改良的灵敏度/较低灵敏度（S/LS）检测法，对从高危人群中收集的存档横断面样本进行检测，可以方便可靠地估计近期HIV-1的高发病率; 2）主要的循环HIV亚型是进化枝B，在pol基因的RT/蛋白酶区域几乎没有重组证据，这是最常见的重组位点。此外，所产生的数据将提供有关事件（循环）HIV中常见的抗逆转录病毒耐药突变的信息，我们预测在这些主要未经治疗的人群中将不存在这些突变。PI是IHV/UMD的资深科学家，在该地区开展合作流行病学/病毒学研究方面经验丰富，并将与亨利杰克逊基金会的HIV分子表征专家以及加勒比地区的HVTN临床研究人员合作。这两个相关项目将利用现有的已表征血清/血浆样本，这些样本将在IHV（CDC IND的参与实验室）使用S/LS检测试剂盒进行分析，以提供发生率数据。使用两阶段算法准确表征事件样本，然后在通常包括重组断点的基因组的RT/蛋白酶区域中对至少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（每个研究中心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。创新是在使用一个修改的S/LS检测算法，以快速确定发病率估计和准确地识别事件的样品，并在使用重叠的RT PCR的全基因组测序的病毒RNA从事件的血清（无细胞）样品。