Disease progression by infecting HIV-1 subtype in a seroconverter cohort in sub-Saharan Africa.
Disease progression by infecting HIV-1 subtype in a seroconverter cohort in sub-Saharan Africa.
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DOI：
10.1097/qad.0000000000000012
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发表时间：
2013-11-13
期刊：
影响因子：
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通讯作者：
IAVI Africa HIV Prevention Partnership
中科院分区：
文献类型：
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作者：
Amornkul PN;Karita E;Kamali A;Rida WN;Sanders EJ;Lakhi S;Price MA;Kilembe W;Cormier E;Anzala O;Latka MH;Bekker LG;Allen SA;Gilmour J;Fast PE;IAVI Africa HIV Prevention Partnership
描述非洲人中 HIV-1 亚型的免疫学、病毒学和临床 HIV 疾病进展，并有详细记录的 HIV 感染估计日期 (EDI)。未来的队列。从东部和南部非洲的血清发病队列中招募了过去 12 个月内记录有 HIV-1 感染的成年人和青少年，并每隔 3-6 个月进行一次随访。每次就诊时收集血液用于淋巴细胞亚群和病毒载量测定。 Pol 对第一个阳性样本进行测序以确定亚型。抗逆转录病毒治疗前的疾病进展通过三个事件发生时间终点来衡量：CD4+细胞计数350个细胞/μl或更少，病毒载量测量至少1×105拷贝/ml，以及临床艾滋病。从2006年到2011年，肯尼亚、卢旺达、南非、乌干达和赞比亚的9个研究中心招募了615名参与者； 579 例 (94.1%) 已完成病毒亚型分析。主要亚型是 C (256, 44.2%)、A (209, 36.1%) 和 D (84, 14.5%)。在 Cox 回归分析中调整年龄、性别和人类白细胞抗原等位基因后，C 亚型感染参与者在所有三个终点上的进展速度都快于 A 亚型 [CD4+ 风险比 1.60，95%（置信区间）CI 1.16，2.20；病毒载量风险比 1.59，95% CI 1.12，2.25；艾滋病风险比 1.60，95% CI 1.11，2.31）。与 A 亚型感染者相比，D 亚型感染者更快地达到高病毒载量（风险比 1.61，95% CI 1.01，2.57），并且进展为艾滋病的速度几乎是 A 亚型感染者的两倍（风险比 1.93，95% CI 1.21，3.09）。 HIV 疾病进展的亚型特异性差异表明，在规划 HIV 项目以及设计和定义 HIV 预防试验的临床终点时，应考虑当地亚型分布。
To describe immunologic, virologic, and clinical HIV disease progression by HIV-1 subtype among Africans with well documented estimated dates of HIV infection (EDIs). Prospective cohort. Adults and youth with documented HIV-1 infection in the past 12 months were recruited from seroincidence cohorts in East and Southern Africa and followed at 3–6 month intervals. Blood for lymphocyte subset and viral load determination was collected at each visit. Pol was sequenced from the first positive specimen to ascertain subtype. Preantiretroviral therapy disease progression was measured by three time-to-event endpoints: CD4+ cell count 350 cells/μl or less, viral load measurement at least 1 × 105 copies/ml, and clinical AIDS. From 2006 to 2011, 615 participants were enrolled at nine research centers in Kenya, Rwanda, South Africa, Uganda, and Zambia; 579 (94.1%) had viral subtyping completed. Predominant subtypes were C (256, 44.2%), A (209, 36.1%), and D (84, 14.5%). After adjustment for age, sex, and human leukocyte antigen alleles in Cox regression analyses, subtype C-infected participants progressed faster than subtype A to all three endpoints [CD4+ hazard ratio 1.60, 95% (confidence interval) CI 1.16, 2.20; viral load hazard ratio 1.59, 95% CI 1.12, 2.25; and AIDS hazard ratio 1.60, 95% CI 1.11, 2.31). Subtype D-infected participants reached high viral load more rapidly (hazard ratio 1.61, 95% CI 1.01, 2.57) and progressed nearly twice as fast to AIDS compared to subtype A (hazard ratio 1.93, 95% CI 1.21, 3.09). Subtype-specific differences in HIV disease progression suggest that the local subtype distribution be considered when planning HIV programs and designing and defining clinical endpoints for HIV prevention trials.