Muscatello Antonio, Nozza Silvia, Fabbiani Massimiliano, De Benedetto Ilaria, Ripa Marco, Dell'acqua Raffaele, Antinori Andrea, Pinnetti Carmela, Calcagno Andrea, Ferrara Micol, Focà Emanuele, Quiros-Roldan Eugenia, Ripamonti Diego, Campus Marco, Maurizio Celesia Benedetto, Torti Carlo, Cosco Lucio, Di Biagio Antonio, Rusconi Stefano, Marchetti Giulia, Mussini Cristina, Gulminetti Roberto, Cingolani Antonella, D'ettorre Gabriella, Madeddu Giordano, Franco Antonina, Orofino Giancarlo, Squillace Nicola, Gori Andrea, Tambussi Giuseppe, Bandera Alessandra
Infectious Diseases Unit; Department of Internal Medicine; IRCCS Ca' Granda Foundation Maggiore Hospital; Milan, Italy.
Clinic of Infectious Diseases; San Raffaele Hospital; University Vita Salute; Milan, Italy.
Pathog Immun. 2020 Feb 24;5(1):8-33. doi: 10.20411/pai.v5i1.341. eCollection 2020.
Viral load peak and immune activation occur shortly after exposure during acute or early HIV infection (AEHI). We aimed to define the benefit of early start of antiretroviral treatment (ART) during AEHI in terms of immunological recovery, virological suppression, and treatment discontinuation.
Patients diagnosed with AEHI (Fiebig stages I-V) during 2008-2014 from an analysis of 20 Italian centers.
This was an observational, retrospective, and multicenter study. We investigated the effect of early ART (defined as initiation within 3 months from AEHI diagnosis) on time to virological suppression, optimal immunological recovery (defined as CD4 count ≥500/µL, CD4 ≥30%, and CD4/CD8 ≥1), and first-line ART regimen discontinuation by Cox regression analysis.
There were 321 patients with AEHI included in the study (82.9% in Fiebig stage III-V). At diagnosis, the median viral load was 5.67 log copies/mL and the median CD4 count was 456 cells/µL. Overall, 70.6% of patients started early ART (median time from HIV diagnosis to ART initiation 12 days, IQR 6-27). Higher baseline viral load and AEHI diagnosis during 2012-2014 were independently associated with early ART. HBV co-infection, baseline CD4/CD8 ≥1, lower baseline HIV-RNA, and AEHI diagnosis in recent years (2012-2014) were independently associated with a shorter time to virological suppression. Early ART emerged as an independent predictor of optimal immunological recovery after adjustment for baseline CD4 (absolute and percentage count) and CD4/CD8 ratio. The only independent predictor of first-line ART discontinuation was an initial ART regimen including > 3 drugs.
In a large cohort of well-characterized patients with AEHI, we confirmed the beneficial role of early ART on CD4+ T-cell recovery and on rates of CD4/CD8 ratio normalization. Moreover, we recognized baseline CD4/CD8 ratio as an independent factor influencing time to virological response in the setting of AEHI, thus giving new insights into research of immunological markers associated with virological control.
在急性或早期HIV感染（AEHI）期间，暴露后不久会出现病毒载量峰值和免疫激活。我们旨在确定在AEHI期间尽早开始抗逆转录病毒治疗（ART）在免疫恢复、病毒学抑制和治疗中断方面的益处。
通过对20个意大利中心的分析，纳入2008 - 2014年期间诊断为AEHI（Fiebig分期I - V期）的患者。
这是一项观察性、回顾性多中心研究。我们通过Cox回归分析研究了早期ART（定义为在AEHI诊断后3个月内开始治疗）对病毒学抑制时间、最佳免疫恢复（定义为CD4细胞计数≥500/µL、CD4≥30%且CD4/CD8≥1）以及一线ART方案中断的影响。
本研究共纳入321例AEHI患者（82.9%为Fiebig III - V期）。诊断时，病毒载量中位数为5.67 log拷贝/mL，CD4细胞计数中位数为456个/µL。总体而言，70.6%的患者开始了早期ART（从HIV诊断到开始ART的中位时间为12天，四分位间距为6 - 27天）。较高的基线病毒载量以及2012 - 2014年期间的AEHI诊断与早期ART独立相关。HBV合并感染、基线CD4/CD8≥1、较低的基线HIV - RNA以及近年来（2012 - 2014年）的AEHI诊断与较短的病毒学抑制时间独立相关。在对基线CD4（绝对计数和百分比计数）以及CD4/CD8比值进行调整后，早期ART成为最佳免疫恢复的独立预测因素。一线ART中断的唯一独立预测因素是初始ART方案包含超过3种药物。
在一大群特征明确的AEHI患者中，我们证实了早期ART对CD4 + T细胞恢复以及CD4/CD8比值正常化率的有益作用。此外，我们认识到基线CD4/CD8比值是影响AEHI情况下病毒学反应时间的独立因素，从而为与病毒学控制相关的免疫标志物研究提供了新的见解。
