Targeting HIV myeloid and central nervous system reservoirs for HIV cure.

Purpose of review: Myeloid vs. CD4 + T-cell reservoirs have received less attention for HIV cure strategies, mainly due to more limited access to tissues andchallenging in vitro and in vivo models, including modeling how myeloid cells affect HIV-associated neurocognitive disorder (HAND). This review highlights recent studies providing insights intomyeloid viral reservoirs, new methods to study them, and the strategies to target them.

Recent findings: In addition to studies describing replication competent virus derived from blood monocytes, which correlates with HAND, myeloid-derived virus can be characterized in clinical samples, such as the blood, using virion immunocapture. Characterization of monocyte subsets and pro-inflammatory markers in the blood can also help detect HAND. New humanized mouse models and in vitro organoid models have improved our ability to study central nervous system (CNS) reservoirs and inflammation. Strategies targeting the CNS vs. peripheral reservoirs may need to be fundamentally different to limit inflammation and which may contribute toHAND.

Summary: Insights provided by these recent studies should challenge the field to employ these methods for myeloid reservoir and HAND detection in preclinical and clinical trial studies. Future HIV cure proposals can aim to include a myeloid reservoir component to help guide the design of strategies for inclusive cure strategies.