Comparative plasma pro-inflammatory cytokine levels in people living with HIV who use opioids and cannabis concurrently versus non-users in Kampala, Uganda: a cross-sectional study

To determine and compare plasma levels of inflammasome-associated pro-inflammatory cytokines (IL-1β, IL-18, IL-33, IL-6, IL-8, IL-15, and TNF-α) between people living with HIV who use both opioids and cannabis and those with no substance use, and to evaluate the associations of these markers with CD4⁺ T-cell count, duration of antiretroviral therapy, age, and sex. Using a Luminex multiplex immunoassay, we measured pro-inflammatory cytokines in PLWH ( n = 78; 35 concurrent opioid and cannabis users and 43 non-users). Concurrent users exhibited higher median cytokine concentrations than non-users, with statistically significant elevations in IL-15 (106.5 vs. 78.4 pg/mL, IQR: 82–118.3 vs. 63.7–103; p = 0.015) and IL-18 (1573.8 vs. 1195.1 pg/mL, IQR: 1136.1–1722.3 vs. 881.7–1573.4; p = 0.0295). In multivariable analyses, only IL-15 remained significantly associated with concurrent users, with elevated levels specifically observed among male users (GMR = 1.30, 95% CI: 1.00–1.67, FDR = 0.095). None of the other factors, including CD4 + T cell count, duration on antiretroviral therapy (ART), and age, showed a significant association with inflammatory markers.