Jiang Wei, Luo Zhenwu, Martin Lisa, Wan Zhuang, Fu Pingfu, Wagner Amanda, Ling Binhua, Heath Sonya L, Haque Azizul, McRae-Clark Aimee
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, 29425, United States.
Divison of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, 29425, United States.
Curr HIV Res. 2018;16(2):143-150. doi: 10.2174/1570162X16666180703151208.
The role and mechanism of drug use or abuse in Antiretroviral Therapy (ART)-treated HIV disease are not completely known.
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.
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).
These results suggest that drug use prevents immune reconstitution in HIV-infected individuals despite long-term ART treatment and viral suppression.
药物使用或滥用在接受抗逆转录病毒疗法（ART）治疗的HIV疾病中的作用和机制尚不完全清楚。
为了研究药物使用对HIV发病机制的影响，而不受到HIV复制和ART依从性的干扰，我们首先通过多元回归测试分析了来自我们临床数据库的103名接受病毒抑制性ART治疗的HIV阳性受试者的数据。
我们发现，与HIV阳性非药物使用者相比，HIV阳性药物使用者的CD4 + T细胞计数较低，但CD8 + T细胞计数较高，并且在控制性别和年龄后，药物使用和最低CD4 + T细胞计数均与CD4 + T细胞恢复独立相关。接下来，我们招募了四个研究组的个体，即无任何物质使用的HIV阴性和HIV阳性受试者、目前使用非法药物（非注射可卡因或大麻）的HIV阴性和HIV阳性受试者。所有HIV阳性受试者均通过ART治疗实现了病毒抑制（≥2年）。值得注意的是，与其他三个研究组相比，HIV阳性药物使用者的血浆抗CD4 IgG水平升高，这仅在HIV阳性药物使用者中与CD4 + T细胞计数减少呈负相关。HIV阳性非药物使用者在接受ART后CD4 + T细胞恢复显著增加，但HIV阳性药物使用者则不然。从HIV阳性药物使用者血浆中纯化的抗CD4 IgGs在体外通过抗体依赖性细胞毒性（ADCC）诱导CD4 + T细胞死亡。
这些结果表明，尽管进行了长期的ART治疗和病毒抑制，但药物使用会阻止HIV感染者的免疫重建。
