Opioid substitution therapies significantly reduce the frequency of injection drug use (Kwiatkowski and Booth 2001; Pettes et al. 2010), decrease HIV transmission risk (MacArthur et al. 2012; Platt et al. 2016), and reduce drug-related mortality (Mathers et al. 2013) and the risk of opioid overdose (Volkow et al. 2014). Further, improved ARV outcomes among PWH have been reported with opioid substitution therapies, including the uptake and retention on ARV, medication adherence rates, and viral suppression (Low et al. 2016; Mukandavire et al. 2017). The two main medications used for opioid substitution therapy include methadone, a MOR full agonist, and buprenorphine, a MOR partial agonist and partial antagonist of KOR (Noble and Marie 2018). In comparison to methadone, buprenorphine has been shown to have fewer pharmacodynamic interactions with ARVs and causes less opioid withdrawal symptoms potentially due to its partial agonism on MOR, but also due to its high affinity and long duration of MOR binding (Walsh et al. 1994; McCance-Katz 2005; Whelan and Remski 2012). Further, differential proinflammatory and neurotoxic effects have been noted for various opioid treatments (Boland et al. 2014; Fitting et al. 2014b; Carvallo et al. 2015; Dutta and Roy 2015). In primary astrocytes, agonist-selective actions at MOR and KOR can be clearly demonstrated (Bohn et al. 2000; Belcheva et al. 2003; McLennan et al. 2008; Hahn et al. 2010), and we found that morphine, methadone, and buprenorphine differentially increase ROS and [Ca2+]i alone or following Tat co-exposure (Fitting et al. 2014b). Morphine can enhance HIV-1-induced production of cytokines and specifically chemokines (El-Hage et al. 2008a; Dave 2012; El-Hage et al. 2014), while other opioids including methadone, oxycodone, buprenorphine, and DAMGO can decrease inflammatory function and decrease monocyte migration (Boland et al. 2014; Carvallo et al. 2015; Jaureguiberry-Bravo et al. 2016; Chilunda et al. 2019).