US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA.
Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Med. 2022 Sep 9;3(9):622-635.e3. doi: 10.1016/j.medj.2022.06.009. Epub 2022 Jul 22.
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).
分析性治疗中断（ATI）研究评估了潜在诱导 HIV-1 感染者缓解的策略，但通常受到样本量的限制。我们合并了四项研究的数据，这些研究测试了三种干预措施（ATI 前使用伏立诺他/羟氯喹/马拉维若、ATI 前使用 Ad26/MVA 疫苗、ATI 期间使用 VRC01 抗体输注）。
评估了合并这些参与者数据的统计学有效性。使用配对相关性、统计检验和 Cox 生存模型评估了 11 个变量，包括 HIV-1 病毒载量在诊断时、Fiebig 阶段和 CD4 T 细胞计数。
参与者具有同质的人口统计学和临床特征。由于在接受 ATI 后接受 VRC01 输注的参与者中观察到抗病毒作用，因此将这些参与者排除在分析之外，允许对 53 名参与者进行汇总分析。病毒反弹时间与感染初期测量的变量显著相关：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，急性 HIV-1 感染时更高的病毒载量与更快的病毒反弹相关，这表明在开始 ART 之前的 HIV-1 感染的初始阶段对多年后 ATI 后的病毒反弹有强烈影响。
这项工作得到了 Henry M. Jackson 基金会军事医学进步与美国陆军之间的合作协议（W81XWH-18-2-0040）和 I4C Martin Delaney 协作实验室（5UM1AI126603-05）的部分资助。
