Medications for opioid use disorder shape immune responses during chronic HIV infection.

People living with HIV (PLWHs) have higher risk of opioid use disorder (OUD). Whether medications for opioid use disorder (MOUDs) change immune responses in HIV infection is unknown. We examined the immune profiles in PLWHs before and 3 months after initiation of the μ opioid receptor agonist methadone, partial agonist buprenorphine, and antagonist naltrexone. Using single-cell DOGMA-seq, we profiled 29,462 peripheral blood immune cells in 12 PLWHs. We found that naltrexone treatment increased type I interferon (IFN) responses while buprenorphine increased tumor necrosis factor (TNF) responses in cytotoxic T cell population. We found that HIV+ cells in PLWHs with OUD upregulated PTPN13 and TAF5L, both of which are associated with HIV replication. We found trends suggesting increased HIV RNA expression after methadone and decreased HIV RNA expression after buprenorphine and naltrexone initiation. Overall, PLWHs treated with MOUD had improved immune responses and decreased HIV expression.