Thymulin is a thymic peptide important for the maturation and differentiation of immature thymocytes, which have been found to be depressed in patients with low-level CD4+ cell recovery despite viral control. Substance use is associated with faster progression of HIV disease, which has been ascribed to poor adherence to antiretroviral medication. Recent findings of an association between cocaine use and decline in CD4+ cell counts independent of antiretroviral adherence indicate alternative mechanisms for disease progression. We evaluated the relationship between thymulin activity, CD4+ and CD8+ cell counts and the CD4+/CD8+ ratio, and the covariate effects of substance use cross-sectionally in 80 HIV+ active substance users and over 12 months in 40 participants. Thymulin activity was analyzed in plasma using a modification of the sheep rosette bioassay. Thymulin activity was negatively associated with cocaine use (β = −0.908,95% CI: −1.704, −0.112; p = 0.026). Compared to those who do not use cocaine, cocaine users were 37% less likely to have detectable thymulin activity (RR = 0.634, 95% CI: 0.406, 0.989 p = 0.045) and were 75 times more likely to show a decrease in thymulin activity (OR = 74.7, 95% CI: 1.59, 3519.74; p = 0.028) over time. CD4+ cell count was positively associated with thymulin activity (β = 0.127, 95% CI: 0.048,0.205; p = 0.002), detectable thymulin activity was 2.32 times more likely in those with a CD4 cell count ≥200 cells/μl (RR = 2.324, 95% CI: 1.196, 4.513, p = 0.013), and those with an increase in CD4 cell counts were more likely to show an increase in thymulin activity (OR = 1.02, 95% CI: 1.00, 1.034; p = 0.041) over time. Thymulin activity is predictive of HIV disease progression and is depressed in cocaine users independent of antiretroviral treatment (ART) and HIV viral load. Understanding the mechanisms for accelerated HIV disease progression provides opportunities to find alternative strategies to counteract immunosuppression.
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机译：胸腺素是一种胸腺肽，对未成熟胸腺细胞的成熟和分化很重要，尽管有病毒控制，但在低水平CD4 + 细胞恢复的患者中胸腺素却被抑制。药物的使用与HIV疾病的更快发展有关，这归因于对抗逆转录病毒药物的依从性差。可卡因的使用与CD4 + 细胞计数下降之间的关联的最新发现，这些结果独立于抗逆转录病毒的依从性，表明疾病发展的其他机制。我们评估了胸腺素活性，CD4 + 和CD8 + 细胞计数与CD4 + / CD8 + 之间的关系。比例和物质使用的协变量效应在80名HIV + 活性物质使用者中横断面，在40多个参与者中超过12个月。使用改良的羊玫瑰花生物测定法分析血浆中的胸腺素活性。胸腺素活性与可卡因的使用负相关（β==-0.908,95％CI：-1.704，-0.112； p == 0.026）。与不使用可卡因的人相比，可卡因使用者具有可检出的胸腺素活性的可能性降低了37％（RR = 340.634，95％CI：0.406，0.989 p = 0.045），并且胸腺素活性降低的可能性高75倍（OR ＝ 74.7，95％CI：1.59，3519.74； p ＝ 0.028）。 CD4 + 细胞计数与胸腺素活性呈正相关（β= 0.127，95％CI：0.048,0.205; p = 0.002），可检测到的胸腺素活性是CD4细胞计数的可能性的2.32倍≥200个细胞/μl（RR = 2.324，95％CI：1.196，4.513，p = 0.013），CD4细胞计数增加的细胞更可能显示胸腺素活性增加（OR = 1.02，95％CI ：1.00，1.034； p ＝ 0.041）。胸腺素活性可预测HIV疾病的进展，可卡因使用者的胸腺素活性可降低，而与抗逆转录病毒治疗（ART）和HIV病毒载量无关。了解加速HIV疾病进展的机制为寻找替代免疫抑制的替代策略提供了机会。
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