Article Sidebar
Main Article Content
Abstract
Introduction: Despite effective antiretroviral therapy (ART), major depressive disorder (MDD) remains highly prevalent in people living with HIV (PLWH). A subset of these patients develops treatment-resistant depression (TRD), creating a significant clinical burden. The "cytokine hypothesis" proposes that residual immune activation drives this resistance. This study aimed to evaluate whether serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) constitute a distinct biological signature of TRD, independent of viral load and smoking status.
Methods: We conducted a cross-sectional case-control study (N=120) between January 2023 and June 2025. Participants were virally suppressed HIV-positive individuals stratified into three groups (n=40 each): (1) TRD (non-response > 2 antidepressants); (2) Treatment-responsive depression (T-Resp); and (3) Non-depressed controls (NDC). Smoking status (pack-years) was quantified. Cytokines were measured via high-sensitivity ELISA. Data were normalized using Log-10 transformation. We employed ANCOVA (adjusting for age, BMI, and smoking) and multivariate logistic regression to assess associations.
Results: The TRD group exhibited significantly higher serum IL-6 and TNF-α compared to the T-Resp and NDC groups (p < 0.001). Although smoking prevalence was higher in the TRD group (45%), ANCOVA confirmed that depression status remained significantly associated with elevated cytokines after adjusting for smoking (F(2,116) = 42.5, p < 0.001). Logistic regression identified IL-6 as a robust correlate of TRD (Adjusted OR 2.15; 95% CI 1.45–3.18) with no multicollinearity (VIF=1.32). ROC analysis indicated high diagnostic accuracy for IL-6 (AUC=0.88).
Conclusion: Elevated proinflammatory cytokines are strongly associated with TRD in PLWH, independent of viral replication and nicotine use. These findings support the potential utility of IL-6 as a stratification biomarker for immunomodulatory adjunctive therapies.
Keywords
Article Details
As our aim is to disseminate original research article, hence the publishing right is a necessary one. The publishing right is needed in order to reach the agreement between the author and publisher. As the journal is fully open access, the authors will sign an exclusive license agreement.
The authors have the right to:
- Share their article in the same ways permitted to third parties under the relevant user license.
- Retain copyright, patent, trademark and other intellectual property rights including research data.
- Proper attribution and credit for the published work.
For the open access article, the publisher is granted to the following right.
- The non-exclusive right to publish the article and grant right to others.
- For the published article, the publisher applied for the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
