HIV-Exposed Uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa and are highly susceptible to disease caused by encapsulated bacteria in the first year of life. The mechanism of this increased risk is still poorly understood. We therefore investigated if HIV exposure dysregulates HEU infant immunity and if this is amplified by human herpes virus infection (HHV). Here, we compared monocyte enzymatic function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HUU infants. We demonstrate altered monocyte phagosomal function and B cell subset homeostasis, and lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-Tetanus Toxoid (TT) IgG titers in HEU compared to HUU infants. There was no difference in the prevalence of HHV infection between HEU and HUU infants. Our findings suggest that even in the era of antiretroviral therapy (ART)-mediated viral suppression, HIV exposure dysregulates monocyte and B cell function during a vulnerable period of immune maturation in infancy. This may contribute to the high rates of invasive bacterial disease and pneumonia in HEU infants.

中文翻译：

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抗逆转录病毒治疗时代未感染 HIV 的非洲婴儿的单核细胞酶功能缺陷和抑制性免疫表型

HIV 暴露未感染 (HEU) 婴儿是撒哈拉以南非洲地区快速增长的人口，并且在出生后的第一年极易感染由包裹细菌引起的疾病。这种风险增加的机制仍然知之甚少。因此，我们调查了 HIV 暴露是否会导致 HEU 婴儿免疫力失调，以及这是否会被人类疱疹病毒感染 (HHV) 放大。在这里，我们比较了 HEU 和 HUU 婴儿的单核细胞酶功能、先天性和适应性免疫细胞表型以及疫苗诱导的抗体反应。我们证明了单核细胞吞噬体功能和 B 细胞亚群稳态的改变，以及较低的疫苗诱导的抗b 型流感嗜血杆菌( Hib)与 HUU 婴儿相比，HEU 中的抗破伤风类毒素 (TT) IgG 滴度。HEU 和 HUU 婴儿的 HHV 感染率没有差异。我们的研究结果表明，即使在抗逆转录病毒疗法 (ART) 介导的病毒抑制时代，在婴儿期免疫成熟的脆弱时期，HIV 暴露也会使单核细胞和 B 细胞功能失调。这可能导致 HEU 婴儿侵袭性细菌疾病和肺炎的高发病率。