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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

[ Vol. 16 , Issue. 2 ]

Author(s):

Wei Jiang*, Zhenwu Luo, Lisa Martin, Zhuang Wan, Pingfu Fu, Amanda Wagner, Binhua Ling, Sonya L. Heath, Azizul Haque and Aimee McRae-Clark   Pages 143 - 150 ( 8 )

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 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:

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

Affiliation:

Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, 29425, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, 29425, Divison of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, 29425, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, 29425, Department of Population and Quantitative Health Science, Case Western Reserve University, Cleveland, OH 44106, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, 29425, Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, 70112, Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, 29425, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, 29425

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