Abstract
A unique population of HIV-1 infected individuals can control infection without antiretroviral therapy. These individuals fall into a myriad of categories based on the degree of control (low or undetectable viral load), the durability of control over time and the underlying mechanism (i.e., possession of protective HLA alleles or the absence of critical cell surface receptors). In this study, we examine a cohort of HIV-1 infected individuals with a documented history of sustained low viral loads in the absence of therapy. Through in vitro analyses of cells from these individuals, we have determined that infected individuals with naturally low viral loads are capable of controlling spreading infection in vitro in a CD8+ T-cell dependent manner. This control is lost when viral load is suppressed by antiretroviral therapy and correlates with a clinical CD4:CD8 ratio of <1. Our results support the conclusion that HIV-1 controllers with low, but detectable viral loads may be controlling the virus due to an effective CD8+ T-cell response. Understanding the mechanisms of control in these subjects may provide valuable understanding that could be applied to induce a functional cure in standard progressors.
Highlights
Human immunodeficiency virus type-1 (HIV-1) infection causes disease by causing immunosuppression (Shearer, 1998; Elfaki, 2014)
We recruited antiretroviral therapy (ART) naïve HIV-1 seropositive donors with viral loads below 2,000 copies/mL which we define as low viral load (LVL) donors, donors with a history of high viral loads (HVLs), elite controllers (ECs), or normal donors (Table 1)
HVLs were less susceptible to infection, with no difference between HVLs suppressed on therapy and those that are therapy naïve
Summary
Human immunodeficiency virus type-1 (HIV-1) infection causes disease by causing immunosuppression (Shearer, 1998; Elfaki, 2014). The average CD4+ T cell count is 1,000 cells/μL. HIV-1 infection causes a drop of 60 cells/uL per year on average (Schwartländer et al, 1993; Patrikar et al, 2014; Parsa et al, 2020). When the CD4+ T-cell count falls below 200 cells/uL, a person is at increased risk of opportunistic infections and malignancies (Egger et al, 2002; Institute of Medicine (US) Committee on Social Security HIV Disability Criteria, 2010; Opportunistic Infections Project Team of the Collaboration of Observational Hiv Epidemiological Research in Europe (Cohere) in EuroCoord, Young et al, 2012; Merci et al, 2017).
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