Aggeu Magalhães Institute, Oswaldo Cruz Foundation/FIOCRUZ,Brazil.
Infectious Diseases and Microbiology Department,University of Pittsburgh,USA.
Epidemiol Infect. 2018 Jul;146(10):1293-1300. doi: 10.1017/S0950268818001218. Epub 2018 Jun 21.
Reducing the risk of human immunodeficiency virus type 1 (HIV-1) transmission is still a public health priority. The development of effective control strategies relies on the quantification of the effects of prophylactic and therapeutic measures in disease incidence. Although several assays can be used to estimate HIV incidence, these estimates are limited by the poor performance of these assays in distinguishing recent from long-standing infections. To address such limitation, we have developed an assay to titrate p24-specific IgG3 antibodies as a marker of recent infection. The assay is based on a recombinant p24 protein capable to detect total IgG antibodies in sera using a liquid micro array and enzyme-linked immunosorbent assay. Subsequently, the assay was optimised to detect and titrate anti-p24 IgG3 responses in a panel of sequential specimens from seroconverters over 24 months. The kinetics of p24-specific IgG3 titres revealed a transient peak in the 4 to 5-month period after seroconversion. It was followed by a sharp decline, allowing infections with less than 6 months to be distinguished from older ones. The developed assay exhibited a mean duration of recent infection of 144 days and a false-recent rate of ca. 14%. Our findings show that HIV-1 p24-specific IgG3 titres can be used as a tool to evaluate HIV incidence in serosurveys and to monitor the efficacy of vaccines and other transmission control strategies.
降低人类免疫缺陷病毒 1 型(HIV-1)传播的风险仍然是公共卫生的重点。有效控制策略的发展依赖于量化预防和治疗措施对疾病发病率的影响。虽然可以使用几种检测方法来估计 HIV 的发病率,但这些估计受到这些检测方法在区分近期和长期感染方面的性能不佳的限制。为了解决这个限制,我们开发了一种检测方法来滴定 p24 特异性 IgG3 抗体作为近期感染的标志物。该检测方法基于一种重组 p24 蛋白,该蛋白能够使用液体微阵列和酶联免疫吸附试验检测血清中的总 IgG 抗体。随后,优化了该检测方法,以检测和滴定在 24 个月内血清转换的连续标本中 p24 特异性 IgG3 反应。p24 特异性 IgG3 滴度的动力学在血清转换后 4 至 5 个月期间出现短暂峰值。随后急剧下降,从而能够区分不到 6 个月的感染和更久的感染。开发的检测方法显示近期感染的平均持续时间为 144 天,假近期感染率约为 14%。我们的研究结果表明,HIV-1 p24 特异性 IgG3 滴度可作为评估血清学调查中 HIV 发病率的工具,并监测疫苗和其他传播控制策略的效果。