buprenorphine and AIDS-Dementia-Complex

HIV-1 enters the CNS within two weeks after peripheral infection and results in chronic neuroinflammation that leads to HIV associated neurocognitive disorders (HAND) in more than 50% of infected people. HIV enters the CNS by transmigration of infected monocytes across the blood brain barrier. Intravenous drug abuse is a major risk factor for HIV-1 infection, and opioids have been shown to alter the progression and severity of HAND. Methadone and buprenorphine are opioid derivates that are used as opioid maintenance therapies. They are commonly used to treat opioid dependency in HIV infected substance abusers, but their effects on monocyte migration relevant to the development of cognitive impairment are not well characterized.. Here, we will discuss the effects of opioids and opioid maintenance therapies on the inflammatory functions of monocytes and macrophages that are related to the development of neuroinflammation in the context of HIV infection.

Topics: AIDS Dementia Complex; Analgesics, Opioid; Blood-Brain Barrier; Buprenorphine; Cell Movement; HIV Infections; Humans; Maintenance Chemotherapy; Methadone; Monocytes; Narcotic Antagonists; Narcotics; Substance Abuse, Intravenous

Approximately 15-40% of people living with HIV develop HIV-associated neurocognitive disorders, HAND, despite successful antiretroviral therapy. There are no therapies to treat these disorders. HIV enters the CNS early after infection, in part by transmigration of infected monocytes. Currently, there is a major opioid epidemic in the United States. Opioid use disorder in the context of HIV infection is important because studies show that opioids exacerbate HIV-mediated neuroinflammation that may contribute to more severe cognitive deficits. Buprenorphine is an opioid derivate commonly prescribed for opiate agonist treatment. We used the EcoHIV mouse model to study the effects of buprenorphine on cognitive impairment and to correlate these with monocyte migration into the CNS. We show that buprenorphine treatment prior to mouse EcoHIV infection prevents the development of cognitive impairment, in part, by decreased accumulation of monocytes in the brain. We propose that buprenorphine has a novel therapeutic benefit of limiting the development of neurocognitive impairment in HIV-infected opioid abusers as well as in nonabusers, in addition to decreasing the use of harmful opioids. Buprenorphine may also be used in combination with HIV prevention strategies such as pre-exposure prophylaxis because of its safety profile.

Topics: AIDS Dementia Complex; Animals; Antigens, Ly; Brain; Buprenorphine; Chronic Disease; Cognitive Dysfunction; Disease Models, Animal; HIV Infections; Inflammation; Male; Mice, Inbred C57BL; Monocytes; Phenotype; Viral Load

HIV infection of the CNS causes neuroinflammation and damage that contributes to the development of HIV-associated neurocognitive disorders (HAND) in greater than 50% of HIV-infected individuals, despite antiretroviral therapy (ART). Opioid abuse is a major risk factor for HIV infection. It has been shown that opioids can contribute to increased HIV CNS pathogenesis, in part, by modulating the function of immune cells. HIV enters the CNS within two weeks after peripheral infection by transmigration of infected monocytes across the blood brain barrier (BBB). CD14

Topics: AIDS Dementia Complex; Buprenorphine; Cell Adhesion; Cells, Cultured; Chemokine CCL2; Chemotaxis, Leukocyte; GPI-Linked Proteins; Humans; Inflammation; Intercellular Adhesion Molecule-1; Lipopolysaccharide Receptors; Monocytes; Nuclear Pore Complex Proteins; Opioid-Related Disorders; Receptors, IgG; Receptors, Opioid, kappa; Receptors, Opioid, mu; THP-1 Cells; Transendothelial and Transepithelial Migration; Vascular Cell Adhesion Molecule-1