Human Immunodeficiency Virus reservoir in macrophages (HIV-1 macrophage reservoir)

HIV reservoirs in macrophages consist of long-lived myeloid cells, such as tissue-resident macrophages and microglia, that harbor integrated HIV-1 proviral DNA and persist despite suppressive antiretroviral therapy (ART) (Honeycutt et al., 2017, Nature Medicine). Unlike CD4+ T cells, macrophages are relatively resistant to the cytopathic effects of the virus, allowing them to serve as stable, long-term sources of infectious virions in various anatomical sites, including the brain, lungs, and gut (Ganor et al., 2019, Journal of Virology). These reservoirs contribute significantly to chronic immune activation and tissue-specific pathologies, most notably HIV-associated neurocognitive disorders (HAND), where infected microglia drive neuroinflammation (Koppensteiner et al., 2012, Journal of Virology). Therapeutic strategies targeting these reservoirs focus on 'shock and kill' approaches using latency-reversing agents like TLR7 agonists or HDAC inhibitors, as well as 'block and lock' methods aimed at permanent epigenetic silencing of the provirus (NIH/NIAID, 2023). Eradication remains a major challenge due to the difficulty of delivering drugs across the blood-brain barrier and the unique metabolic state of infected macrophages compared to lymphoid cells.

Other names

Macrophage-resident HIVMyeloid HIV reservoirLatent HIV in macrophagesHIV-infected macrophagesTissue-resident macrophage HIV reservoir

Inhibition of viral replication via antiretroviral therapy (ART), induction of viral expression through latency-reversing agents (Shock and Kill), or permanent transcriptional silencing (Block and Lock) (Ganor et al., 2019; Honeycutt et al., 2017).