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

Author(s): Wei Jiang*, Zhenwu Luo, Lisa Martin, Zhuang Wan, Pingfu Fu, Amanda Wagner, Binhua Ling, Sonya L. Heath, Azizul Haque, Aimee McRae-Clark

Journal Name: Current HIV Research

Volume 16 , Issue 2 , 2018


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Graphical Abstract:


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.

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Article Details

VOLUME: 16
ISSUE: 2
Year: 2018
Published on: 15 August, 2018
Page: [143 - 150]
Pages: 8
DOI: 10.2174/1570162X16666180703151208
Price: $65

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