T-cell responses in primary HIV-1 infection

Important immunological events, especially involving T cells, occur during primary HIV-1 infection. The qualitative nature of the primary immune response to the virus may determine long-term outcome. Whereas CD4 T cells are being rapidly depleted, CD8 T cells play an important role in the initial control of viral replication. There is significant individual variability in the extent of viral control. Understanding the mechanisms underlying these differences and the causes of the development of dysfunctional T-cell responses will allow the identification of opportunities for therapeutic intervention that might change the long-term outcome.

Recent studies have revealed early dysfunction of T cells demonstrating increased expression of PD-1, CTLA-4 and reduced expression of CD127. Those studies suggest disruption of the interaction between CD4 and CD8 T cells. In addition, a few regions, mainly within the Gag protein, have been highlighted as potentially important targets for effective immune responses inducing viral control.

Despite recent studies emphasizing the critical nature of acute HIV-1 infection, current intervention strategies have failed to influence disease progression. Recent findings have indicated potential new strategies to re-enable functional properties of T cells and direct these responses towards critical regions of the virus.