Reactivation kinetics of HIV-1 and susceptibility of reactivated latently infected CD4⁺ T cells to HIV-1-specific CD8⁺ T cells

The "shock and kill" model of human immunodeficiency virus type 1 (HIV-1) eradication involves the induction of transcription of HIV-1 genes in latently infected CD4+ T cells, followed by the elimination of these infected CD4⁺ T cells by CD8⁺ T cells or other effector cells. CD8⁺ T cells may also be needed to control the spread of new infection if residual infected cells are present at the time combination antiretroviral therapy (cART) is discontinued. In order to determine the time frame needed for CD8⁺ T cells to effectively prevent the spread of HIV-1 infection, we examined the kinetics of HIV transcription and virus release in latently infected cells reactivated ex vivo. Isolated resting, primary CD4⁺ T cells from HIV-positive (HIV⁺) subjects on suppressive regimens were found to upregulate cell-associated HIV-1 mRNA within 1 h of stimulation and produce extracellular virus as early as 6 h poststimulation. In spite of the rapid kinetics of virus production, we show that CD8⁺ T cells from 2 out of 4 viremic controllers were capable of effectively eliminating reactivated autologous CD4⁺ cells that upregulate cell-associated HIV-1 mRNA. The results have implications for devising strategies to prevent rebound viremia due to reactivation of rare latently infected cells that persist after potentially curative therapy.