原发性人类免疫缺陷病毒感染期间延迟抗逆转录病毒治疗对端粒长度的影响。

Impact of Delaying Antiretroviral Treatment During Primary Human Immunodeficiency Virus Infection on Telomere Length.

作者信息

Raffenberg Marieke, Engel Tanja, Schoepf Isabella C, Kootstra Neeltje A, Reiss Peter, Braun Dominique L, Thorball Christian W, Fellay Jacques, Kouyos Roger D, Ledergerber Bruno, Günthard Huldrych F, Tarr Philip E

机构信息

University Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Bruderholz, Switzerland.

Department of Intensive Care Medicine, Luzerner Kantonsspital, Lucerne, Switzerland.

出版信息

J Infect Dis. 2021 Nov 22;224(10):1775-1784. doi: 10.1093/infdis/jiab186.

DOI:10.1093/infdis/jiab186

PMID:33822976

Abstract

BACKGROUND

Telomere length (TL) shortens during aging, HIV seroconversion, and untreated chronic HIV infection. It is unknown whether early antiretroviral therapy (ART) start is associated with less TL shortening during primary HIV infection (PHI).

METHODS

We measured TL in peripheral blood mononuclear cells by quantitative polymerase chain reaction in participants of the Zurich PHI Study with samples available for ≥6 years. We obtained univariable/multivariable estimates from mixed-effects models and evaluated the association of delaying ART start or interrupting ART with baseline and longitudinal TL.

RESULTS

In 105 participants with PHI (median age 36 years, 9% women), median ART delay was 25, 42, and 60 days, respectively, in the first (shortest), second, and third (longest) ART delay tertile. First ART delay tertile was associated with longer baseline TL (P for trend = .034), and longer TL over 6 years, but only with continuous ART (P < .001), not if ART was interrupted ≥12 months (P = .408). In multivariable analysis, participants in the second and third ART delay tertile had 17.6% (5.4%-29.7%; P = .004) and 21.5% (9.4%-33.5%; P < .001) shorter TL, after adjustment for age, with limited effect modification by clinical variables.

CONCLUSIONS

In PHI, delaying ART start for even a matter of weeks was associated with significant and sustained TL shortening.

摘要

背景

端粒长度（TL）在衰老、HIV血清转化和未经治疗的慢性HIV感染过程中会缩短。目前尚不清楚在原发性HIV感染（PHI）期间早期开始抗逆转录病毒治疗（ART）是否与较少的TL缩短相关。

方法

我们通过定量聚合酶链反应测量了苏黎世PHI研究中样本可获得≥6年的参与者外周血单个核细胞中的TL。我们从混合效应模型中获得单变量/多变量估计值，并评估延迟开始ART或中断ART与基线和纵向TL的关联。

结果

在105名PHI参与者中（中位年龄36岁，9%为女性），在首次（最短）、第二次和第三次（最长）ART延迟三分位数中，ART延迟的中位数分别为25天、42天和60天。首次ART延迟三分位数与更长的基线TL相关（趋势P值 = 0.034），以及6年期间更长的TL，但仅与持续ART相关（P < 0.001），如果ART中断≥12个月则不相关（P = 0.408）。在多变量分析中，在调整年龄后，第二次和第三次ART延迟三分位数的参与者TL缩短了17.6%（5.4%-29.7%；P = 0.004）和21.5%（9.4%-33.5%；P < 0.001），临床变量的效应修正有限。