Tissue reservoirs of HIV

Tissue reservoirs of HIV may promote the persistent immunopathology responsible for non-AIDS morbidity and data support multifocal reactivation from tissues as the source of viral rebound during antiretroviral therapy (ART) interruption. The heterogeneity of tissue reservoirs and incomplete knowledge about their composition are obstacles to an HIV cure.

In addition to the higher concentration of infected CD4 T cells found in both central lymphoid tissues and gut, specific subsets of CD4 T cells appear to play a disproportionate role in HIV persistence. Recently, a subset of central memory T cells enriched in lymph node germinal centers called T-follicular helper cells has been identified that expresses more viral RNA and occupies an anatomic niche inaccessible to cytotoxic T lymphocyte killing. Additional observations suggest that antiretroviral drug (ARV) concentrations may be lower in some tissues, raising the possibility for localized, low-level viral replication. Finally, some recent data implicate the persistence of infected, non-CD4 T-cell types in tissues during ART.

The retention of infected cells in a wide variety of tissues, often with distinct viral and cellular characteristics, underscores the importance of studying tissue reservoirs in the development and assessment of cure strategies. Both inhibitory ARVs and latency-reversing drugs must reach these sites, and novel strategies may be needed to attack virus in cells as variable as T-follicular helper cells and macrophages.