Early cART Leads to Enhanced T Cell Function in HIV Infection
Limiting acute viremia results in enhanced functionality of HIV-specific CD4+ and CD8+ T cells
THURSDAY, May 23, 2019 (HealthDay News) -- Early combination antiretroviral therapy (cART) leads to persistent functional T cell responses in most individuals with hyperacute HIV-1 infection, according to a study published online May 22 in Science Translational Medicine.
Zaza M. Ndhlovu, Ph.D., from the Africa Health Research Institute in Durban, South Africa, and colleagues examined the impact of cART on CD4+ T cell loss and exhaustion of HIV-specific CD8+ T cell responses by examining the evolution of immune responses in acutely infected individuals initiating treatment before peak viremia.
The researchers observed a rapid decline in viral load and diminished magnitude of HIV-specific (tetramer +) CD8+ T cell responses with immediate treatment of Fiebig stages I and II infection versus untreated donors. A strong positive correlation was seen between cumulative viral antigen exposure before full cART-induced suppression and immune responses. For early-treated individuals, HIV-specific CD8+ T responses were characterized by increased CD127 and BCL-2 expression, greater in vitro interferon-γ secretion, and enhanced differentiation into effector memory cells. Reduced expression of genes associated with activation and apoptosis and up-regulation of prosurvival genes was seen in transcriptional analysis of tetramer+ CD8+ T cells from treated individuals. Compared with untreated HIV-infected individuals, early treatment also resulted in robust HIV-specific CD4+ T cell responses.
"These data open up the possibility of harnessing immune responses generated under early treatment as a first critical step in the path toward immune-mediated HIV cure or remission strategies," the authors write.