Drug Use is Associated with Anti-CD4 IgG-mediated CD4+ T Cell Death and Poor CD4+ T Cell Recovery in Viral-suppressive HIV-infected Individuals Under Antiretroviral Therapy

Abstract

Background. The role and mechanism of drug use or abuse in antiretroviral therapy (ART)-treated HIV disease are not completely known. Methods. To investigate the impact of drug use on HIV pathogenesis without confounding by HIV replication and ART adherence, we first analyzed the data from our clinical database in 103 HIV+ subjects with viral-suppressed ART treatment by a multiple regression test. Results. We found that HIV+ drug users had lower CD4+ T cell counts but higher CD8+ T cell counts compared to HIV+ non-drug users, and both drug use and nadir CD4+ T cell counts was independently associated with CD4+ T cell recovery after controlling for sex and age. Next, we enrolled individuals from four study groups, HIV-negative and HIV+ subjects without any substance use, HIV-negative and HIV+ subjects with current illicit drug use (either non-injection cocaine or cannabis). All HIV+ subjects were viral-suppressed with ART treatment (≥ 2 years). Notably, HIV+ drug users had increased plasma anti-CD4 IgG levels compared to the other three study groups which were inversely correlated with decreased CD4+ T cell counts only in drug use in HIV disease. There was a significant increase in CD4+ T cell recovery following ART in HIV+ non-drug users but not in HIV+ drug users. Anti-CD4 IgGs purified from plasma of HIV+ drug users induced CD4+ T cell death in vitro through antibody-dependent cytotoxicity (ADCC). Conclusion. These results suggest that drug use prevents immune reconstitution in HIV-infected individuals despite long-term ART treatment and viral suppression.

Intersecting Pandemics: Impact of SARS-CoV-2 (COVID-19) Protective Behaviors on People Living With HIV, Atlanta, Georgia

“…Tobacco use, particularly cigarette smoking, is associated with COVID-19 severity, 8 and tobacco use may interact with other substances to further compromise the immune system. 9 , 10 Alcohol and other drug use also suppresses immune responses, 11 – 13 particularly among people living with HIV. 14 Along with underlying health conditions, substance use raises concerns for COVID-19 morbidity and mortality in people living with HIV.…”

Link between Interleukin-23 and Anti-CD4 Autoantibody Production in Antiretroviral-Treated HIV-Infected Individuals

“…Our published studies (10,11,24) were the first to determine that pathological anti-CD4 IgGs from immunologic nonresponders on virally suppressive ART (CD4 cell counts , 350 cells/ml) mediated CD4 1 T cell death via ADCC, which plays a role in poor CD4 1 T cell recovery from ART. Up to 25% of HIV-infected individuals are nonresponders (25) and demonstrate increased morbidity and mortality (4,(26)(27)(28).…”

Chronic cannabis smoking-enriched oral pathobiont drives behavioral changes, macrophage infiltration, and increases β-amyloid protein production in the brain

“…For individuals with cannabis use disorder, we assessed exclusionary psychiatric diagnoses using appropriate modules of the Mini-International Neuropsychiatric Interview, as described in our previous study [23] . Briefly, The M.I.N.I., a brief structured interview, was to assess current Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) diagnoses.…”