Macrophages: the neglected barrier to eradication.

PURPOSE OF REVIEW: There has been a shift towards HIV-1 eradication research in the last three years, yet much is still unknown about the precise role that macrophages will play in any such strategy. This review attempts to summarize the latest data on this subject. RECENT
FINDINGS: A new generation of histone deacetylase inhibitors, ITF2357, belinostat, givinostat, panobinostat, and the cancer drug JQ1, have been shown to induce viral reactivation in a monocyte cell line. In macrophages chronically infected with HIV-1 in vitro, drugs blocking pre-integration steps have demonstrated poor efficacy in controlling viral replication in comparison to protease inhibitors, thus questioning whether drugs can control this reservoir following histone deacetylase inhibition. Finally, non-human primate data suggest that CD8+ T cells may not be able to clear infected macrophages.
SUMMARY: Given these data highlighting the barriers to addressing the macrophage reservoir, functional rather than sterilizing cure may be a realistic goal. More research on macrophages is needed and animal models may prove useful in future HIV-1 eradication studies by offering a clinically relevant way to study macrophage infection in vivo.