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

作者：Jiang Wei^*; Luo Zhenwu; Martin Lisa; Wan Zhuang; Fu Pingfu; Wagner Amanda; Ling Binhua; Heath Sonya L; Haque Azizul; McRae Clark Aimee

来源：Current HIV Research, 2018, 16(2): 143-150.

DOI：10.2174/1570162X16666180703151208

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

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.

• 出版日期2018