HIV can cause white matter damage (Gosztonyi et al. 1994; Langford et al. 2002; Xuan et al. 2013) even with less severe forms of HAND (Chen et al. 2009; Leite et al. 2013; Correa et al. 2015). Diffusion tensor magnetic resonance imaging (DTI) demonstrates white matter damage early in HAND (Ragin et al. 2004; Stubbe-Drger et al. 2012; Leite et al. 2013; Correa et al. 2015). White matter deficits are associated with cognitive impairment, including shortfalls in memory (Ragin et al. 2005), executive function (Correa et al. 2015), motor speed (Wu et al. 2006; Stubbe-Drger et al. 2012), and perhaps depression (Schmaal and van Velzen 2019). Preclinical studies in simian immunodeficiency virus- (SIV-) infected rhesus macaques (Marcario et al. 2008) and HIV-infected humanized mice (Boska et al. 2014) support the clinical findings. Injury to oligodendrocytes (OLs) can occur very early in the disease (see review, Liu et al. 2016b). Viral proteins, including Tat, gp120, and Nef, have been implicated in OL injury in vitro (Kimura-Kuroda et al. 1994; Bernardo et al. 1997; Radja et al. 2003; Nukuzuma et al. 2012; Zou et al. 2015), and in animal models in vivo (Radja et al. 2003; Hauser et al. 2009; Zou et al. 2015). Importantly, Tat has been detected in OLs in the brains of AIDS patients (Del Valle et al. 2000).