人类免疫缺陷病毒在衰老过程中持续性和储存库大小的性别差异。
Sex Differences in Human Immunodeficiency Virus Persistence and Reservoir Size During Aging.
机构信息
University of California San Diego, La Jolla, California, USA.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory School of Medicine, Atlanta, Georgia, USA.
出版信息
Clin Infect Dis. 2022 Aug 24;75(1):73-80. doi: 10.1093/cid/ciab873.
BACKGROUND
Sex differences in human immunodeficiency virus (HIV) reservoir dynamics remain underexplored.
METHODS
Longitudinal samples from virally suppressed midlife women (n = 59, median age 45 years) and age-matched men (n = 31) were analyzed retrospectively. At each time point, we measured sex hormones (by means of enzyme-linked immunosorbent assay) and cellular HIV DNA and RNA (by means of digital droplet polymerase chain reaction). Number of inducible HIV RNA+ cells, which provides an upper estimate of the replication-competent reservoir, was quantified longitudinally in a different subset of 14 women, across well-defined reproductive stages. Mixed-effects models included normalized reservoir outcomes and sex, time since antiretroviral therapy (ART) initiation, and the sex-by-time interaction as predictors.
RESULTS
At ART initiation, women and men had median (interquartile range [IQR]) CD4+ T-cell counts of 204/μL (83-306/μL) versus 238/μL (120-284/μL), respectively; median ages of 45 (42-48) versus 47 (43-51) years; and median follow-up times of 79.2/μL (60.5-121.1/μL) versus 66.2/μL (43.2-80.6/μL) months. We observed a significant decline of total HIV DNA over time in both men and women (P < .01). However, the rates of change differed significantly between the sexes (P < .01), with women having a significantly slower rate of decline than men, more pronounced with age. By contrast, the levels of inducible HIV RNA increased incrementally over time in women during reproductive aging (P < .01).
CONCLUSIONS
In contrast to men, in whom the HIV reservoir steadily declines with aging, the HIV reservoir in women is more dynamic. Total HIV DNA (including intact and defective genomes) declines more slowly in women than in men, while the inducible HIV RNA+ reservoir, which is highly enriched in replication-competent virus, increases in women after menopause.
背景
人类免疫缺陷病毒 (HIV) 储存库的性别差异仍未得到充分研究。
方法
回顾性分析了 59 名病毒抑制的中年女性（中位年龄 45 岁）和 31 名年龄匹配男性的纵向样本。在每个时间点，我们通过酶联免疫吸附测定法（ELISA）测量性激素，并通过数字液滴聚合酶链反应（PCR）测量细胞 HIV DNA 和 RNA。在另一个不同的 14 名女性亚组中，我们纵向定量了可诱导 HIV RNA+细胞的数量，该数量提供了复制能力储存库的上限估计。混合效应模型将正常化的储存库结果与性别、抗逆转录病毒治疗 (ART) 开始后的时间以及性别与时间的相互作用作为预测因子。
结果
在开始接受 ART 时，女性和男性的 CD4+ T 细胞计数中位数（四分位距 [IQR]）分别为 204/μL（83-306/μL）和 238/μL（120-284/μL）；中位年龄分别为 45（42-48）和 47（43-51）岁；中位随访时间分别为 79.2/μL（60.5-121.1/μL）和 66.2/μL（43.2-80.6/μL）个月。我们观察到男性和女性的总 HIV DNA 随时间呈显著下降（P<0.01）。然而，性别之间的变化率有显著差异（P<0.01），女性的下降速度明显慢于男性，且随年龄增长更为明显。相比之下，在女性生殖衰老过程中，可诱导的 HIV RNA 水平随时间呈递增趋势（P<0.01）。
结论
与男性不同，男性随着年龄的增长，HIV 储存库稳定下降，而女性的 HIV 储存库更具动态性。女性的总 HIV DNA（包括完整和缺陷基因组）下降速度慢于男性，而可诱导的 HIV RNA+储存库在女性绝经后增加，该储存库富含具有复制能力的病毒。
Zotero 插件