HIV-1 GENETIC VARIATION IN INFECTED HEMOPHILIACS OVER TIME

这是一个研究HIV-1序列的范围和模式的项目 部分HIV-1感染患者与血友病患者的差异 增长和发展研究，一项多中心合作，以定义 HIV-1感染对社会、神经心理和生理的影响 血友病男性儿童和青少年的生长发育。最初， 研究将集中在病毒载量的数量和质量上的差异 和快速进展区HIV-1选定区域的序列变异 被定义为参与者的每立方米CD4计数下降75% 基线(入学学习)和第二次年度考试，进展缓慢 定义为CD4计数保持稳定或增加的参与者 基线和年度访问之间的两年时间段。套式底漆 聚合酶链式反应将用于扩增env的可变区， 在前病毒DNA和cDNA中发现的游离病毒粒子中都有Gag和nef 血浆。随后将进行克隆和序列分析，以检测 并对艾滋病毒进化过程中的突变积累进行分类- 1寄主免疫选择性制约下的“准种” 系统。将从每个个体中对至少20个克隆进行测序 几个连续的时间点。

This is a project to examine the extent and pattern of HIV-1 sequence divergence within selected HIV-1-infected patients from the Hemophilia Growth and Development Study, a multi-center collaboration to define the effects of HIV-1 infection on the social, neuropsychological, and physical growth of male children and adolescents with hemophilia. Initially the study will focus on quantitative and qualitative differences in virus load and sequence variation at selected HIV-1 regions of rapid progressors defined as participants whose CD4 counts per mm3 decline by 75% between baseline (study entry) and second annual exam, and slow progressors defined as participants whose CD4 counts remain stable or increase over the 2-year period between baseline and annual visit two. Nested primer polymerase chain reaction will be used to amplify variable regions of env, gag, and nef in both proviral DNA and cDNA of free virions found in plasma. This will be followed by cloning and sequence analysis to detect and catalog the accumulation of mutations during the evolution of the HIV- 1 "quasispecies" under the selective constraints of the host immune system. At least 20 clones will be sequenced from each individual from several sequential time points.