KEMRI/Wellcome Trust Research Programme, Kilifi, Kenya.
Department of Translational Medicine, Lund University, Sweden.
Clin Infect Dis. 2021 Sep 7;73(5):832-841. doi: 10.1093/cid/ciab139.
Acute retroviral syndrome (ARS) is associated with human immunodeficiency virus type 1 (HIV-1) subtype and disease progression, but the underlying immunopathological pathways are poorly understood. We aimed to elucidate associations between innate immune responses during hyperacute HIV-1 infection (hAHI) and ARS.
Plasma samples obtained from volunteers (≥18.0 years) before and during hAHI, defined as HIV-1 antibody negative and RNA or p24 antigen positive, from Kenya, Rwanda, Uganda, Zambia, and Sweden were analyzed. Forty soluble innate immune markers were measured using multiplexed assays. Immune responses were differentiated into volunteers with stronger and comparatively weaker responses using principal component analysis. Presence or absence of ARS was defined based on 11 symptoms using latent class analysis. Logistic regression was used to determine associations between immune responses and ARS.
Of 55 volunteers, 31 (56%) had ARS. Volunteers with stronger immune responses (n = 36 [65%]) had increased odds of ARS which was independent of HIV-1 subtype, age, and risk group (adjusted odds ratio, 7.1 [95% confidence interval {CI}: 1.7-28.8], P = .003). Interferon gamma-induced protein (IP)-10 was 14-fold higher during hAHI, elevated in 7 of the 11 symptoms and independently associated with ARS. IP-10 threshold >466.0 pg/mL differentiated stronger immune responses with a sensitivity of 84.2% (95% CI: 60.4-96.6) and specificity of 100.0% (95% CI]: 90.3-100.0).
A stronger innate immune response during hAHI was associated with ARS. Plasma IP-10 may be a candidate biomarker of stronger innate immunity. Our findings provide further insights on innate immune responses in regulating ARS and may inform the design of vaccine candidates harnessing innate immunity.
急性逆转录病毒综合征（ARS）与人类免疫缺陷病毒 1 型（HIV-1）亚型和疾病进展相关，但潜在的免疫病理途径仍知之甚少。本研究旨在阐明急性 HIV-1 感染（hAHI）期间固有免疫反应与 ARS 之间的相关性。
我们分析了来自肯尼亚、卢旺达、乌干达、赞比亚和瑞典的志愿者在 hAHI 期间和之前采集的血浆样本，hAHI 定义为 HIV-1 抗体阴性，RNA 或 p24 抗原阳性。使用多重分析测定了 40 种可溶性固有免疫标志物。使用主成分分析将免疫反应分为较强和相对较弱的反应。使用潜在类别分析根据 11 种症状定义 ARS 的存在或不存在。使用逻辑回归确定免疫反应与 ARS 之间的相关性。
在 55 名志愿者中，31 名（56%）出现 ARS。具有较强免疫反应的志愿者（n=36 [65%]）发生 ARS 的几率增加，这与 HIV-1 亚型、年龄和风险组无关（调整后的优势比，7.1 [95%可信区间{CI}：1.7-28.8]，P=0.003）。干扰素诱导蛋白（IP）-10 在 hAHI 期间升高了 14 倍，在 11 种症状中的 7 种症状中升高，并且与 ARS 独立相关。IP-10 阈值>466.0 pg/mL 区分了较强的免疫反应，其敏感性为 84.2%（95%CI：60.4-96.6），特异性为 100.0%（95%CI：90.3-100.0）。
hAHI 期间固有免疫反应较强与 ARS 相关。血浆 IP-10 可能是较强固有免疫的候选生物标志物。我们的研究结果提供了关于固有免疫反应调节 ARS 的进一步见解，并可能为利用固有免疫的疫苗候选物的设计提供信息。
