Malatinkova Eva, De Spiegelaere Ward, Bonczkowski Pawel, Kiselinova Maja, Vervisch Karen, Trypsteen Wim, Johnson Margaret, Verhofstede Chris, de Looze Danny, Murray Charles, Kinloch-de Loes Sabine, Vandekerckhove Linos
HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.
Division of Infection and Immunity, Royal Free Hospital, London, United Kingdom.
Elife. 2015 Oct 6;4:e09115. doi: 10.7554/eLife.09115.
Persistent reservoirs remain the major obstacles to achieve an HIV-1 cure. Prolonged early antiretroviral therapy (ART) may reduce the extent of reservoirs and allow for virological control after ART discontinuation. We compared HIV-1 reservoirs in a cross-sectional study using polymerase chain reaction-based techniques in blood and tissue of early-treated seroconverters, late-treated patients, ART-naïve seroconverters, and long-term non-progressors (LTNPs) who have spontaneous virological control without treatment. A decade of early ART reduced the total and integrated HIV-1 DNA levels compared with later treatment initiation, but not reaching the low levels found in LTNPs. Total HIV-1 DNA in rectal biopsies did not differ between cohorts. Importantly, lower viral transcription (HIV-1 unspliced RNA) and enhanced immune preservation (CD4/CD8), reminiscent of LTNPs, were found in early compared to late-treated patients. This suggests that early treatment is associated with some immunovirological features of LTNPs that may improve the outcome of future interventions aimed at a functional cure.
持续性病毒库仍然是实现治愈人类免疫缺陷病毒1型(HIV-1)的主要障碍。早期长期抗逆转录病毒疗法(ART)可能会减少病毒库的规模,并使停药后实现病毒学控制成为可能。我们在一项横断面研究中,使用基于聚合酶链反应的技术,比较了早期接受治疗的血清转化者、晚期接受治疗的患者、未接受过ART的血清转化者以及未经治疗却能自发实现病毒学控制的长期不进展者(LTNP)血液和组织中的HIV-1病毒库。与较晚开始治疗相比,十年的早期ART降低了HIV-1总DNA水平和整合DNA水平,但未达到LTNP中发现的低水平。各队列直肠活检中的HIV-1总DNA没有差异。重要的是,与晚期接受治疗的患者相比,早期接受治疗的患者中发现病毒转录水平较低(HIV-1未剪接RNA)且免疫保存增强(CD4/CD8),这与LTNP的情况相似。这表明早期治疗与LTNP的一些免疫病毒学特征相关,这些特征可能会改善未来旨在实现功能性治愈的干预措施的效果。