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

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.