Buprenorphine Increases HIV-1 Infection In Vitro but Does Not Reactivate HIV-1 from Latency

Background: medication-assisted treatment (MAT) with buprenorphine is now widely prescribed to treat addiction to heroin and other illicit opioids. There is some evidence that illicit opioids enhance HIV-1 replication and accelerate AIDS pathogenesis, but the effect of buprenorphine is unknown. Methods: we obtained peripheral blood mononuclear cells (PBMCs) from healthy volunteers and cultured them in the presence of morphine, buprenorphine, or methadone. We infected the cells with a replication-competent CCR5-tropic HIV-1 reporter virus encoding a secreted nanoluciferase gene, and measured infection by luciferase activity in the supernatants over time. We also surveyed opioid receptor expression in PBMC, genital epithelial cells and other leukocytes by qPCR and western blotting. Reactivation from latency was assessed in J-Lat 11.1 and U1 cell lines. Results: we did not detect expression of classical opioid receptors in leukocytes, but did find nociception/orphanin FQ receptor (NOP) expression in blood and vaginal lymphocytes as well as genital epithelial cells. In PBMCs, we found that at physiological doses, morphine, and methadone had a variable or no effect on HIV infection, but buprenorphine treatment significantly increased HIV-1 infectivity (median: 8.797-fold increase with 20 nM buprenorphine, eight experiments, range: 3.570-691.9, p = 0.0078). Using latently infected cell lines, we did not detect reactivation of latent HIV following treatment with any of the opioid drugs. Conclusions: our results suggest that buprenorphine, in contrast to morphine or methadone, increases the in vitro susceptibility of leukocytes to HIV-1 infection but has no effect on in vitro HIV reactivation. These findings contribute to our understanding how opioids, including those used for MAT, affect HIV infection and reactivation, and can help to inform the choice of MAT for people living with HIV or who are at risk of HIV infection.