Abstract: Antiretroviral therapy (ART) effectively decreases active HIV replication to undetectable levels. Therefore, it greatly improves the quality of life for people living with HIV (PLWH). However, except for a few exceptional cases after stem-cell transplantation from CCR5Δ32 mutation donors, such as in Berlin and London patients, there is no cure for HIV, due to the latent HIV reservoirs harbored in the long-lived HIV permissive cells. HIV quickly rebounds upon the disruption of ART, causing the life-long burden of ART for PLWH in order to control viral replication. Similar to peripheral blood, HIV establishes reservoirs in the brain very early in infection (Putatunda et al., 2019), which is associated with HIV-associated neurocognitive disorders despite ART in PLWH, potentially caused directly by residual HIV replication or indirectly by neuroinflammation. Animal model studies suggest that brain myeloid cells (BMCs) are latently infected and contribute to viral reservoirs in the central nervous system (CNS) (Honeycutt et al., 2016; Avalos et al., 2017). To achieve a cure for HIV, latently infected replication-competent HIV hosted in both periphery and CNS must be targeted by viral eradication strategies.