Research ArticleHIV

Augmentation of HIV-specific T cell function by immediate treatment of hyperacute HIV-1 infection

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Science Translational Medicine  22 May 2019:
Vol. 11, Issue 493, eaau0528
DOI: 10.1126/scitranslmed.aau0528

Keeping it FRESH in HIV

HIV infection affects the immune system beyond infected CD4+ T cells and can cause systemic immune dysfunctions even when the virus is controlled by antiretroviral treatment. To determine how early treatment affects anti-HIV T cell responses, Ndhlovu et al. examined samples from the FRESH cohort, which enables analysis of hyperacute infection. They compared HIV-specific CD8+ T cells from women who initiated treatment within 2 days of HIV diagnosis to those that started treatment during the acute or chronic phase of infection. CD8+ T cells from individuals that started treatment immediately had preserved functionality, likely due to limited viremia. The antiviral capacity of these cells may be a useful goal for HIV vaccine design.

Abstract

Sustained viremia after acute HIV infection is associated with profound CD4+ T cell loss and exhaustion of HIV-specific CD8+ T cell responses. To determine the impact of combination antiretroviral therapy (cART) on these processes, we examined the evolution of immune responses in acutely infected individuals initiating treatment before peak viremia. Immediate treatment of Fiebig stages I and II infection led to a rapid decline in viral load and diminished magnitude of HIV-specific (tetramer+) CD8+ T cell responses compared to untreated donors. There was a strong positive correlation between cumulative viral antigen exposure before full cART-induced suppression and immune responses measured by MHC class I tetramers, IFN-γ ELISPOT, and CD8+ T cell activation. HIV-specific CD8+ T responses of early treated individuals were characterized by increased CD127 and BCL-2 expression, greater in vitro IFN-γ secretion, and enhanced differentiation into effector memory (Tem) cells. Transcriptional analysis of tetramer+ CD8+ T cells from treated persons revealed reduced expression of genes associated with activation and apoptosis, with concurrent up-regulation of prosurvival genes including BCL-2, AXL, and SRC. Early treatment also resulted in robust HIV-specific CD4+ T cell responses compared to untreated HIV-infected individuals. Our data show that limiting acute viremia results in enhanced functionality of HIV-specific CD4+ and CD8+ T cells, preserving key antiviral properties of these cells.

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