Besides being able to infect hNPCs, HIV may also affect their maturation and the fate of neural stem cells. That HIV or gp120 can inhibit adult neurogenesis (Okamoto et al. 2007; Lee et al. 2013; Putatunda et al. 2018) has been the topic of past reviews (Schwartz and Major 2006; Venkatesan et al. 2007; Peng et al. 2008, 2011; Ferrell and Giunta 2014; Hauser and Knapp 2014; Putatunda et al. 2019). How HIV inhibits the self-renewal, tripotential differentiation, and survival of neural progenitors/stem cells or the genesis of adult neurons in the subgranular zone (SGZ) of the dentate gyrus is uncertain. HIV and gp120 [via actions at the same chemokine receptor(s) (Tran and Miller 2005; Li and Ransohoff 2008)] are proposed to modulate the adult neurogenesis via Notch (Fan et al. 2016), by obstructing a cell cycle checkpoint via the activation MAPK-activated protein kinase 2 and Cdc25B/C (Okamoto et al. 2007), or through signaling by platelet-derived growth factor BB (Chao et al. 2014) or BDNF (Lee et al. 2013). The extent that HIV regulates the genesis of neural progenitors within the subventricular zone of the developing CNS through similar mechanisms as in the adult SGZ of the dentate gyrus is uncertain—even though HIV disrupts the generation of neurons and glia during maturation or in adults. For example, MAPK/ERK1/2 enhances p53- and p21-dependent downregulation of cyclin D1 hindering progression through the G1 phase of the cell cycle in hNPCs (Mishra et al. 2010; Malik et al. 2014). Importantly, opioids too can affect the genesis of neurons and glia during maturation or in the adult directly via convergent pathways (Hauser and Knapp 2018; Kibaly et al. 2018) suggesting yet another site of opioid and HIV interactions in dysregulating the creation and fate of new neurons and glia.