Tissue reservoirs of HIV

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Figure 1

A) HIV DNA copies per million CD4 cells present in blood or different gut sites from 8 patients on ART with undetectable plasma virus. B) Ratio of HIV RNA (unspliced, genomic) to HIV DNA providing measures of HIV expression per average infected cell. Horizontal bars = medians; whiskers show standard deviations. Adapted from Yukl et al JID 2010[61]