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

Academic Article

Abstract

  • © 2018 Bentham Science Publishers. 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 HIV+ drug users. 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.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Jiang W; Luo Z; Martin L; Wan Z; Fu P; Wagner A; Ling B; Heath SL; Haque A; McRae-Clark A
  • Start Page

  • 143
  • End Page

  • 150
  • Volume

  • 16
  • Issue

  • 2