晚期HIV感染者长期生存的决定因素：前瞻性PISCIS队列研究。
Determinants of long-term survival in late HIV presenters: The prospective PISCIS cohort study.
作者信息
Martin-Iguacel Raquel, Reyes-Urueña Juliana, Bruguera Andreu, Aceitón Jordi, Díaz Yesika, Moreno-Fornés Sergio, Domingo Pere, Burgos-Cibrian Joaquín, Tiraboschi Juan Manuel, Johansen Isik Somuncu, Álvarez Hortensia, Miró Josep M, Casabona Jordi, Llibre Josep M
机构信息
Centre of Epidemiological Studies of HIV/AIDS and STI of Catalonia (CEEISCAT), Health Department, Generalitat de Catalunya, Badalona, Spain.
Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
出版信息
EClinicalMedicine. 2022 Aug 3;52:101600. doi: 10.1016/j.eclinm.2022.101600. eCollection 2022 Oct.
BACKGROUND
Late HIV diagnosis (i.e CD4≤350 cells/µL) is associated with poorer outcomes. However, determinants of long-term mortality and factors influencing immune recovery within the first years after antiretroviral treatment (ART) initiation are poorly defined.
METHODS
From PISCIS cohort, we included all HIV-positive adults, two-year survivors after initiating ART between 2005-2019. The primary outcome was all-cause mortality according to the two-year CD4 count. We used Poisson regression. The secondary outcome was incomplete immune recovery (i.e., two-year CD4<500 cells/µL). We used logistic regression and propensity score matching.
FINDINGS
We included 2,719 participants (16593·1 person-years): 1441 (53%) late presenters (LP) and 1278 non-LP (1145 non-LP with two-year CD4 count >500 cells/µL, reference population). Overall, 113 patients (4·2%) died. Mortality was higher among LP with two-year CD4 count 200-500 cells/µL (aMRR 1·95[95%CI:1·06-3·61]) or <200 cells/µL (aMRR 4·59[2·25-9·37]).Conversely, no differences were observed in participants with two-year CD4 counts >500 cells/µL, regardless of being initially LP or non-LP (aMRR 1·05[0·50-2·21]). Mortality rates within each two-year CD4 strata were not affected by the initial CD4 count at ART initiation (test-interaction, = 0·48). The stronger factor influencing immune recovery was the CD4 count at ART initiation. First-line integrase-inhibitor-(INSTI)-based regimens were associated with reduced mortality compared to other regimens (aMRR 0·54[0·31-0·93]) and reduced risk of incomplete immune recovery in LP (aOR 0·70[0·52-0·95]).
INTERPRETATION
Two-year immune recovery is a good early predictor of long-term mortality in LP after surviving the first high-risk 2 years. Nearly half experienced a favorable immune recovery with a life expectancy similar to non-LP. INSTI-based regimens were associated with higher rates of successful immune recovery and better survival compared to non-INSTI regimens.
FUNDING
Southern-Denmark University, Danish AIDS-foundation, and Region of Southern Denmark.
背景
晚期HIV诊断（即CD4≤350个细胞/微升）与较差的预后相关。然而，长期死亡率的决定因素以及抗逆转录病毒治疗（ART）开始后头几年内影响免疫恢复的因素尚不清楚。
方法
从PISCIS队列中，我们纳入了所有HIV阳性成年人，他们在2005年至2019年期间开始接受ART治疗并存活了两年。主要结局是根据两年CD4计数的全因死亡率。我们使用泊松回归。次要结局是免疫恢复不完全（即两年CD4<500个细胞/微升）。我们使用逻辑回归和倾向得分匹配。
结果
我们纳入了2719名参与者（16593.1人年）：1441名（53%）晚期就诊者（LP）和1278名非LP（1145名非LP的两年CD4计数>500个细胞/微升，作为参照人群）。总体而言，113名患者（4.2%）死亡。两年CD4计数为200-500个细胞/微升的LP死亡率更高（调整后死亡率比[aMRR]为1.95[95%置信区间：1.06-3.61]），或<200个细胞/微升的LP死亡率更高（aMRR为4.59[2.25-9.37]）。相反，两年CD4计数>500个细胞/微升的参与者，无论最初是LP还是非LP，均未观察到差异（aMRR为1.05[0.50-2.21]）。每个两年CD4分层内的死亡率不受ART开始时初始CD4计数的影响（检验交互作用，P = 0.48）。影响免疫恢复的更强因素是ART开始时的CD4计数。与其他方案相比，一线基于整合酶抑制剂（INSTI）的方案与死亡率降低相关（aMRR为0.54[0.31-0.93]），且LP免疫恢复不完全的风险降低（调整后比值比[aOR]为0.70[0.52-0.95]）。
解读
在度过最初的高风险两年后存活下来的LP中，两年免疫恢复是长期死亡率的良好早期预测指标。近一半患者经历了良好的免疫恢复，预期寿命与非LP相似。与非INSTI方案相比，基于INSTI的方案与更高的免疫恢复成功率和更好的生存率相关。
资助
南丹麦大学、丹麦艾滋病基金会和南丹麦地区。
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