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

Curr HIV Res. 2018;16(2):143-150. doi: 10.2174/1570162X16666180703151208.


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.

Keywords: CD4+ T cell recovery; HIV; anti-CD4 IgG; antibody-dependent cytotoxicity; antiretroviral therapy; drug use..

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Antiretroviral Therapy, Highly Active
  • CD4 Antigens / antagonists & inhibitors*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology*
  • Female
  • HIV Antibodies / immunology
  • HIV Antibodies / pharmacology*
  • HIV Antibodies / therapeutic use
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / virology*
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / pharmacology*
  • Immunoglobulin G / therapeutic use
  • Male


  • Anti-HIV Agents
  • CD4 Antigens
  • HIV Antibodies
  • Immunoglobulin G