Plasma cytokine levels during acute HIV-1 infection predict HIV disease progression

Abstract

Background Both T cell activation during early HIV-1 infection and soluble markers of immune activation during chronic infection are predictive of HIV disease progression. Although the acute phase of HIV infection is associated with increased pro-inflammatory cytokine production, the relationship between cytokine concentrations and HIV pathogenesis is unknown. Objectives To identify cytokine biomarkers measurable in plasma during acute HIV-1 infection that predict HIV disease progression. Design Study including 40 South African women who became infected with HIV-1 and were followed longitudinally from the time of infection. Methods The concentrations of 30 cytokines in plasma from women with acute HIV-1 infection were measured and associations between cytokine levels and both viral load set-point 12 months post-infection and time taken for CD4 counts to fall below 350 cells/μl were determined using multivariate and Cox proportional-hazards regression. Results We found that the concentrations of 5 plasma cytokines, IL-12p40, IL-12p70, IFN-γ, IL-7 and IL-15, in women with acute infection predicted 66% of the variation in viral load set-point 12 months post infection. IL-12p40, IL-12p70 and IFN-γ were significantly associated with lower viral load whereas IL-7 and IL-15 were associated with higher viral load. Plasma concentrations of IL-12p40 and GM-CSF during acute infection were associated with maintenance of CD4 counts above 350 cells/μl while IL-1α, eotaxin and IL-7 were associated with more rapid CD4 loss. Conclusions A small panel of plasma cytokines during acute HIV-1 infection was predictive of long-term HIV disease prognosis in this group of South African women.

Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

“…2 Levels of TNF-a, IL-6, hs-CRP, and other proinflammatory cytokines are associated with HIV-1 viral load and may predict disease progression, as well as correlate with a higher risk of CVD and all-cause mortality. [42][43][44][45] Our findings corroborate another recent analysis, which reported that only d-dimer, and not IL-6 or hs-CRP, is reduced over the short term in those initiating ARV therapy. 46 Additionally, the reductions in LPS observed here are similar in magnitude to those seen in a previous study 47 ; the similar reductions in the DRV/r and ATV/r arms suggest that these ARV agents do not result in differential levels of LPS, a trigger of persistent immune activation in ARV-treated individuals.…”

Immunovirological parameters and cytokines in HIV infection

“…Others cytokine production can increase viral replication, due the activation role in HIV infected cells, including IL-2, IL-4 and interferon type II (IFN-γ) which, primarly, are required in the support to expansion of antiviral T cells and antibody responses 30 . During the acute phase of HIV-1 infection, was showed 36 that elevated plasma levels of inflammatory cytokines are associated with viremia peaks and can even estimate the time at which the CD4+ T count will drop below 350 cells/mm 3 . Thus it would be important low levels of these cytokine in this critical phase.…”

“…In addition to the initial of the infection, in a cohort study of women at high risk for HIV acquisition, Roberts et al 36 observed that IL-12 and IFN-γ levels were significantly associated with lower VL, but IL-15 and IL-7 with higher VL, and the latter also with lower CD4+ count. These authors demonstrated significant rises in IL-1, IL-2 and IL-7 at approximately six weeks after the infection 36 .…”

The comparison of Th1, Th2, Th9, Th17 and Th22 cytokine profiles in acute and chronic HIV-1 infection

“…Concentrations of IFN-α and IL-15 increase within the 5 days following the onset of measurable plasma viremia. Subsequently, increased concentrations of TNF-α, MCP-1, IL-6, IL-8, IL-18 and IFN-γ are also detected [16]. Cytokines synthesized in early HIV-1 infection can have a complex effect on the host.…”