Abstract
Objective:HIV type 2 (HIV-2) represents an attenuated form of HIV, in which many infected individuals remain ‘aviremic’ without antiretroviral therapy. However, aviremic HIV-2 disease progression exists, and in the current study, we therefore aimed to examine if specific pathological characteristics of CD4+ T cells are linked to such outcome.Design:HIV-seronegative (n = 25), HIV type 1 (HIV-1) (n = 33), HIV-2 (n = 39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n = 13)-infected study participants were enrolled from an occupational cohort in Guinea-Bissau.Methods:CD4+ T-cell differentiation, activation, exhaustion, senescence, and transcription factors were assessed by polychromatic flow cytometry. Multidimensional clustering bioinformatic tools were used to identify CD4+ T-cell subpopulations linked to infection type and disease stage.Results:HIV-2-infected individuals had early and late-differentiated CD4+ T-cell clusters with lower activation (CD38+HLA-DR+) and exhaustion programmed death-1 (PD-1) than HIV-1 and HIV-D-infected individuals. We also noted that aviremic HIV-2-infected individuals possessed fewer individuals. CD4+ T cells with pathological signs compared to other HIV-infected groups. Still, compared to HIV-seronegative individuals, aviremic HIV-2-infected individuals had T-bet+ CD4+ T cells that showed elevated immune activation/exhaustion, and particularly the frequencies of PD-1+ cells were associated with a suboptimal percentage of CD4+ T cells.Conclusion:Increased frequencies of CD4+ T cells with an activated/exhausted phenotype correlate with exacerbated immunodeficiency in aviremic HIV-2-infected individuals. Thus, these findings encourage studies on the introduction of antiretroviral therapy also to individuals with aviremic HIV-2 infection.
Highlights
Untreated HIV type 1 (HIV-1) infection is characterized by progressive decline of CD4þ T cells, resulting in the development of AIDS
The frequency of CD4þ T-cell memory phenotypes was largely similar between the groups, in which only late-differentiated (CD45ROþ CD27À) cells were elevated in HIV-1-infected compared to HIV type 2 (HIV-2)-infected study participants (P < 0.05; Fig. 1b)
The level of programmed death-1 (PD-1)-expressing cells followed similar trends and was reduced on CD4þ T cells in HIV-2 compared to both HIV-1 (P < 0.001) and HIV-2 dually (HIV-D) (P < 0.05) infections (Fig. 1c)
Summary
Untreated HIV type 1 (HIV-1) infection is characterized by progressive decline of CD4þ T cells, resulting in the development of AIDS. Infection with HIV type 2 (HIV2) may progress to AIDS, but the likelihood is reduced (reviewed in [1]). The reason for this difference is not fully elucidated, but it is clear that the plasma viral load set-point in HIV-2-infected individuals is at least one log lower than in HIV-1-infected individuals [2,3]. Even though HIV-2 plasma viremia may emerge, and is predictive of progressive HIV-2 disease [4,5], a large proportion of HIV-2-infected individuals maintain undetectable HIV-2 plasma levels, similar to individuals with untreated aviremic HIV-1 infection (elite controllers) [2,3]. Studies of aviremic HIV-2-infected individuals may provide insights to how protective immunity can be harnessed and translated for future vaccine or curing strategies against both HIV-1 and HIV-2
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