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Review
. 2016 Oct:42:65-70.
doi: 10.1016/j.coi.2016.05.015. Epub 2016 Jun 9.

Challenges and strategies for the eradication of the HIV reservoir

Jason T Kimata  1 , Andrew P Rice  2 , Jin Wang  3
Affiliations
Review

Challenges and strategies for the eradication of the HIV reservoir

Jason T Kimata et al. Curr Opin Immunol. 2016 Oct.

Abstract

Despite the success of highly active antiretroviral therapy (HAART) for inhibiting HIV replication and improving clinical outcomes, it fails to cure infection due to the existence of a stable latent proviral reservoir in memory CD4+ T cells. Because of the longevity of these cells harboring transcriptionally silent proviruses, devising strategies to induce viral gene expression so the host immune response can mediate clearance of the infected cells or the cells can undergo virus-induced cell death, has been of considerable recent interest. Here, we review current knowledge of latency, and the challenges to virus induction and eradication. Novel strategies to reactivate HIV reservoirs more effectively, in combination with immunotherapy, could lead to better clearance of the latent HIV reservoir.

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Figures

Figure 1
Figure 1
Potential strategy for eradicating latently infected memory CD4+ T cells. Although antiretroviral therapy (ART) effectively controls HIV replication, the virus persists as a latently integrated proviral form in resting memory CD4+ T cells. As latency is an efficient immune evasion mechanism, it is of significant interest to devise ways to reactive virus expression in order for infected cells to be recognized by the host immune response and cleared, or for the cells to undergo virus-mediated cell death. However, neither process appears to readily occur following treatment with latency reversing agents. HIV cure strategies should therefore consider approaches to increase these activities. First, immune-mediated clearance of the latently infected CD4+ T cells after reactivation of virus expression could be enhanced by adoptive T cell transfer of broadly specific anti-HIV CTLs and passive immunotherapy with broadly neutralizing antibodies (bNAbs). Second, virus-induced cell killing may be enhanced by sensitizing the cells with small molecule drugs targeting cell survival pathways.
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