分析性治疗中断(ATI)研究评估了可能诱导HIV-1感染者缓解的策略,但通常样本量有限。我们结合了四项研究的数据,这些研究测试了三种干预措施(ATI之前的伏立诺他/羟氯喹/maraviroc,在ATI之前接种Ad26/MVA,和ATI期间VRC01抗体输注)。
评估了来自这些参与者的组合数据的统计有效性。11个变量,包括诊断时的HIV-1病毒载量,Fiebig舞台,和CD4+T细胞计数使用成对相关性进行评估,统计检验,和Cox生存模型.
参与者具有同质的人口统计学和临床特征。因为在ATI后接受VRC01输注的参与者中观察到抗病毒作用,这些参与者被排除在分析之外,允许对53名参与者进行汇总分析。病毒反弹时间与感染开始时测量的变量显着相关:抗逆转录病毒治疗(ART)前病毒载量(HR=1.34,p=0.022),ART启动后病毒抑制时间(HR=1.07,p<0.001),和病毒载量曲线下面积(HR=1.34,p=0.026)。
我们表明,在急性HIV-1感染中,较高的病毒载量与较快的病毒反弹有关。证明ART开始前HIV-1感染的初始阶段对ATI后的病毒反弹有很大影响。
这项工作得到了亨利·M·杰克逊军事医学促进基金会和美国陆军部之间的合作协议(W81XWH-18-2-0040)的支持。这项研究得到了资助,在某种程度上,由美国国家过敏和传染病研究所(AAI20052001)和I4CMartinDelaneyCollabory(5UM1AI126603-05)。
Analytic treatment interruption (ATI) studies evaluate strategies to potentially induce remission in people living with HIV-1 but are often limited in sample size. We combined data from four studies that tested three interventions (vorinostat/hydroxychloroquine/maraviroc before ATI, Ad26/MVA vaccination before ATI, and VRC01 antibody infusion during ATI).
The statistical validity of combining data from these participants was evaluated. Eleven variables, including HIV-1 viral load at diagnosis, Fiebig stage, and CD4+ T cell count were evaluated using pairwise correlations, statistical tests, and Cox survival models.
Participants had homogeneous demographic and clinical characteristics. Because an antiviral effect was seen in participants who received VRC01 infusion post-ATI, these participants were excluded from the analysis, permitting a pooled analysis of 53 participants. Time to viral rebound was significantly associated with variables measured at the beginning of infection: pre-antiretroviral therapy (ART) viral load (HR = 1.34, p = 0.022), time to viral suppression post-ART initiation (HR = 1.07, p < 0.001), and area under the viral load curve (HR = 1.34, p = 0.026).
We show that higher viral loads in acute HIV-1 infection were associated with faster viral rebound, demonstrating that the initial stage of HIV-1 infection before ART initiation has a strong impact on viral rebound post-ATI years later.
This work was supported by a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the US Department of the Army (W81XWH-18-2-0040). This research was funded, in part, by the US National Institute of Allergy and Infectious Diseases (AAI20052001) and the I4C Martin Delaney Collaboratory (5UM1AI126603-05).