NeuroHIV in the context of opioid use disorder

HIV and opioid abuse are interlinked epidemics. Although modern HIV treatments are typically effective at suppressing the virus within the peripheral circulation, HIV still resides in reservoir sites like the brain, which can contribute to the collective cognitive and motor dysfunction of HIV-associated neurocognitive disorder (HAND), also termed neuroHIV. Opioid use/misuse can further contribute to the neuropathology of HIV through multiple mechanisms, including blood–brain barrier breakdown, increasing the recruitment of immune cells and inflammatory mediators, disrupted glutamate and calcium signaling, and release of viral toxins. Additionally, there are numerous drug–drug interactions that can occur between opioids, including those used to treat opioid use disorder, and drugs used to treat HIV. These interactions can result in poorer viral suppression, including within the brain and/or altered opioid efficacy. In the case of opioid use disorder treatment with opioid substitution therapies (such as buprenorphine and methadone), lower exposures lead to greater chance of opioid withdrawal symptoms and relapse, and the cycle of opioid–HIV neuropathogenesis is prolonged. Additional research is needed to further elucidate the mechanisms and identify new therapeutic strategies to reduce the burden of the neuropathology caused by the interlinked epidemics of HIV and comorbid opioid use disorder.