Impact of antiretroviral therapy during primary HIV infection on T-cell immunity after treatment interruption

IF 4.5 3区 医学 Q2 IMMUNOLOGY
Timothy Tipoe, Ane Ogbe, Ming Lee, Helen Brown, Nicola Robinson, Rebecca Hall, Claire Petersen, Heather Lewis, John Thornhill, Fiona Ryan, Julie Fox, Sarah Fidler, John Frater
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Abstract

This study aims to understand the impact of early antiretroviral therapy (ART) on HIV-specific T-cell responses measured after treatment interruption, which may inform strategies to deliver ART-free immune-mediated viral suppression. HIV-specific T-cell immunity was analysed using gamma interferon enzyme-linked immunospot assays in two studies. SPARTAC included individuals with primary HIV infection randomised to 48 weeks of ART (n = 24) or no immediate therapy (n = 37). The PITCH (n = 7) cohort started antiretroviral therapy in primary infection for at least one year, followed by TI. In SPARTAC, participants treated in PHI for 48 weeks followed by TI for 12 weeks, and those who remained untreated for 60 weeks made similar HIV Gag-directed responses (both magnitude and breadth) at week 60. However, the treated group made a greater proportion of novel HIV Gag-directed responses by Week 60, suggestive of a greater reserve to produce new potentially protective responses. In the more intensively followed PITCH study, 6/7 participants showed dominant Gag and/or Pol-specific responses post-TI compared with pre-TI. Although early ART in PHI was not associated with major differences in HIV-specific immunity following TI compared with untreated participants, the potential to make more new Gag-directed responses warrants further investigation as this may inform strategies to achieve ART-free control.

Abstract Image

原发性 HIV 感染期间的抗逆转录病毒疗法对治疗中断后 T 细胞免疫的影响。
本研究旨在了解早期抗逆转录病毒疗法(ART)对治疗中断后测量的 HIV 特异性 T 细胞反应的影响,从而为无 ART 免疫介导的病毒抑制策略提供参考。在两项研究中,使用γ干扰素酶联免疫吸附试验分析了HIV特异性T细胞免疫。SPARTAC 包括原发性 HIV 感染者,他们被随机分配接受 48 周抗逆转录病毒疗法(24 人)或不立即接受治疗(37 人)。PITCH(n = 7)组群在原发性感染时开始抗逆转录病毒治疗至少一年,然后进行TI治疗。在 SPARTAC 中,接受 PHI 治疗 48 周后接受 TI 治疗 12 周的参与者和 60 周内未接受治疗的参与者在第 60 周时的 HIV Gag 定向反应(幅度和广度)相似。然而,治疗组在第 60 周时产生了更大比例的新型 HIV Gag 定向反应,这表明他们有更大的储备来产生新的潜在保护性反应。在更密集跟踪的 PITCH 研究中,与治疗前相比,6/7 的参与者在治疗后出现了明显的 Gag 和/或 Pol 特异性反应。虽然 PHI 中的早期抗逆转录病毒疗法与未接受治疗的参与者相比,与 TI 后 HIV 特异性免疫力的重大差异无关,但产生更多新的 Gag 定向反应的潜力值得进一步研究,因为这可能为实现无抗逆转录病毒疗法控制的策略提供依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
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