Subclinical Iron Overload Hampers the Beneficial Effect of Human Pegivirus (Hpgv) On Disease Progression in Human Immunodeficiency Virus Type-1 Infected Blood Donors

Chattopadhyay Debasish, V. Alice, S. Uma, Rai Arvind
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Abstract

Background: Despite frequent association of Human Pegivirus (HPgV) and Torque Teno Virus (TTV) infections with Human Immunodeficiency Virus type-1 (HIV-1) infection, their roles on HIV-1 disease progression remain unclear. Methods: A prospective study on HIV-1 disease progres sion was undertaken in three HIV-1 infected blood donor subgroups at early asymptomatic stages: Those with HPgV co-infections (n = 60), with TTV co-infections (n = 48) and without the two co-infections (n = 54). Within each subgroup, both replacement and voluntary donors are exam -ined. The markers of HIV-1 disease progression included the following virological and immunological parameters: Rate of increase in plasma HIV-1 viral load, rate of fall in CD4+ T lymphocyte count, serum levels of Tumor necrosis factor alpha (TNF-α), TNF-α receptors (TNFRI and TNFRII), and levels of Nuclear Factor kappa beta (NF-kB) in peripheral blood mononuclear cells (PBMCs). Results: In all three HIV-1 infected subgroups, replacement donors displaying biochemical evidence of iron overload had higher levels of disease progression markers at enrollment and lower symptom-free survival duration on follow up compared to voluntary donors in the same subgroup. Vol untary donors in the HPgV co-infected subgroup showed significantly slower rate of HIV-1 disease progression com pared to voluntary donors in the other two subgroups. Re placement donors in the HPgV co-infected subgroup that showed loss HPgV viraemia at 3 years post-enrollment were associated with faster disease progression compared to those showing persistence of HPgV viraemia at the same point. Conclusion: The present study favors the concept that HPgV co-infection slows down disease progression in HIV-1 infected individuals. However, this beneficial effect may be obliterated due to subclinical iron overload, resulting in loss of HPgV vireamia consequent to fall in peripheral CD4+ T lymphocyte count.
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亚临床铁超载阻碍人佩吉病毒(Hpgv)对人类免疫缺陷病毒1型感染献血者疾病进展的有益作用
背景:尽管人类Pegivirus (HPgV)和Torque Teno Virus (TTV)感染经常与人类免疫缺陷病毒1型(HIV-1)感染相关,但它们在HIV-1疾病进展中的作用尚不清楚。方法:对3个早期无症状阶段HIV-1感染的献血者亚组进行HIV-1疾病进展的前瞻性研究:hpv合并感染(n = 60), TTV合并感染(n = 48)和无两种合并感染(n = 54)。在每个分组中,替代供体和自愿供体都要接受检查。HIV-1疾病进展的标志包括以下病毒学和免疫学参数:血浆HIV-1病毒载量的增加率、CD4+ T淋巴细胞计数的下降率、血清肿瘤坏死因子α (TNF-α)、TNF-α受体(TNFRI和TNFRII)的水平以及外周血单核细胞(PBMCs)中核因子β (NF-kB)的水平。结果:在所有三个HIV-1感染亚组中,与同一亚组的自愿供者相比,显示铁超载生化证据的替代供者在入组时具有更高水平的疾病进展标志物和更短的无症状生存时间。与其他两个亚组的自愿献血者相比,hpv共感染亚组的自愿献血者的HIV-1疾病进展率明显较慢。在hpv共感染亚组中,与在同一时间持续存在hpv病毒血症的人相比,在入组3年后显示hpv病毒血症消失的再安置供者与更快的疾病进展相关。结论:本研究支持hpv合并感染减缓HIV-1感染者疾病进展的概念。然而,这种有益作用可能由于亚临床铁超载而被消除,导致hpv病毒血症的丧失,从而导致外周血CD4+ T淋巴细胞计数下降。
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