Pasternak Alexander O, van Paassen Pien M, Verschoor Yara L, Vroom Jelmer, van Dort Karel A, Maurer Irma, Grijsen Marlous L, Wit Ferdinand W, de Bree Godelieve J, Kootstra Neeltje A, Prins Jan M, Berkhout Ben
Laboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Nat Commun. 2025 Jul 30;16(1):6989. doi: 10.1038/s41467-025-62362-0.
Initiation of antiretroviral therapy (ART) during primary HIV-1 infection (PHI) has been proposed to limit the formation of HIV-1 reservoirs. However, it remains unknown whether temporary ART initiated during PHI has a long-term effect on viral persistence. Here, we longitudinally quantify HIV-1 persistence markers and immunological parameters in the participants (n = 64) of a randomized controlled trial comparing 24 or 60 weeks of temporary ART vs. no treatment during PHI, who subsequently (re)initiated ART during chronic HIV-1 infection (CHI) after a median period of 116 weeks without treatment (ISRCTN59497461). Levels of several HIV-1 persistence markers (cell-associated unspliced RNA, total DNA, and intact DNA) do not significantly differ and strongly positively correlate between early and CHI ART periods in the same participants. Early ART is associated with lower HIV-1 proviral sequence diversity and superior restoration of the CD4/CD8 ratio, as well as lower levels of monocyte activation markers, compared to CHI ART, in the same participants. At CHI ART, intact HIV-1 DNA negatively correlates with HIV-specific T-cell responses. Finally, levels of HIV-1 persistence markers during CHI ART are lower in participants who had been pre-treated during PHI, indicating a long-term suppressive effect of temporary early ART on the persistence of HIV-1 reservoir.
在原发性HIV-1感染(PHI)期间启动抗逆转录病毒疗法(ART),已被提议用于限制HIV-1储存库的形成。然而,在PHI期间启动的短期ART是否对病毒持续性有长期影响仍不清楚。在此,我们纵向量化了一项随机对照试验参与者(n = 64)中的HIV-1持续性标志物和免疫参数,该试验比较了PHI期间24周或60周的短期ART与不治疗的情况,这些参与者随后在慢性HIV-1感染(CHI)期间,在未经治疗的中位116周后(ISRCTN59497461)重新启动了ART。在同一参与者中,几个HIV-1持续性标志物(细胞相关未剪接RNA、总DNA和完整DNA)的水平在早期和CHI ART期间没有显著差异,且呈强正相关。与CHI ART相比,早期ART与较低的HIV-1前病毒序列多样性、更好的CD4/CD8比值恢复以及较低的单核细胞活化标志物水平相关。在CHI ART时,完整的HIV-1 DNA与HIV特异性T细胞反应呈负相关。最后,在PHI期间接受过预处理的参与者中,CHI ART期间的HIV-1持续性标志物水平较低,这表明短期早期ART对HIV-1储存库的持续性具有长期抑制作用。
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