Characteristics and clinical significance of plasma IL‐18, sCD14, and sCD163 levels in patients with HIV‐1 infection

Abstract

Biomarkers of monocyte‐macrophages activation and inflammation in plasma such as interleukin‐18 (IL‐18), soluble leukocyte differentiation antigen 14 (sCD14), and sCD163 are associated with disease severity and prognosis in HIV‐1 infected patients, however, their relationships with efficacy of antiretroviral therapy (ART) need further investigation. We aimed to characterize and explore the clinical significance of plasma IL‐18, sCD14, and sCD163 in this population. This was a retrospective cohort study consisting of HIV‐1 infected patients enrolled in a randomized, controlled, open‐label, noninferiority trial (ALTERLL study), with follow‐up time points including initiation of ART (baseline), 12‐, 24‐ and 48‐weeks of treatment. Plasma levels of IL‐18, sCD14, and sCD163 were measured using the enzyme‐linked immunosorbent assay method. Viral suppression was defined as HIV‐1 RNA < 20 copies/ml. Among the 193 studied patients (median age of 29.0 years, 180 males), IL‐18 and sCD163 had U‐shaped regression curves and sCD14 had an inverted U‐shaped regression curve while the virus was decreased and immune function recovered. Patients with higher levels of IL‐18 or lower levels of sCD163 at baseline were less likely to achieve viral suppression at Week 12 or Week 24 of treatment, respectively. In multivariate analysis, baseline sCD163 ≤ 500 pg/ml (adjusted odds ratio 0.33, 95% confidence interval 0.16–0.68) was independently associated with a lower rate of viral suppression at Week 24 of treatment. In conclusion, we demonstrated different dynamic changes among IL‐18, sCD14, and sCD163 after ART. Baseline sCD163 level could be a potential predictor of early virological response to ART. Further validation and mechanistic research are needed.

Early on-treatment plasma interleukin-18 as a promising indicator for long-term virological response in patients with HIV-1 infection

“…One possible explanation is that long-term virological response may be less affected by baseline viral load and baseline immune function than short-term (48 week) virological responses. This was supported by our previous work showing that lower baseline HIV-1 RNA levels could independently predict higher rates of virological responses at week 48 of ART ( 7 ). In addition, the predictive effectiveness of week 24 IL-18 on long-term virological response is extremely strong, and when they are simultaneously included in the multivariate model, the predictive effectiveness of baseline HIV-1 RNA and baseline CD4+ cell count may appear to be very weak, which is not uncommon in multivariate analysis.…”

“…Numerous studies have revealed that chronic immune inflammation is a hallmark of HIV-1 infection that persists even after several years of successful ART and is associated with noninfectious complications of HIV-1, including cardiovascular disease, non-AIDS malignancies and frailty ( 10 , 11 ). Our recent short-term study demonstrated that plasma IL-18 decreased after initiation of ART up to 24 weeks but rebounded by 48 weeks post-ART initiation ( 7 ). The current study further uncovered the long-term dynamic changes in IL-18, that is, it continued to rise after 48 weeks of ART.…”

“…Long-term virological response was defined as HIV-1 RNA <20 copies/mL at week 144 of treatment. Subgenotypes of the HIV-1 virus were tested with the standard strains selected from the Los Alamos HIV database using Bioedit and MEGA5 software, and mutation sites were identified using the Stanford HIV-resistant database ( Supplementary Table S1 ), which has been described elsewhere ( 7 ).…”

“…We found that the levels of plasma IL-18 showed U-shaped regression curves while the virus decreased and immune function recovered after initiating ART and that the viral suppression rate at week 12 of treatment was higher in patients with lower baseline IL-18. These findings suggested that there may be an inherent institutional association and that IL-18 may be associated with the efficacy of ART ( 7 ).…”

Markers of Inflammation, Tissue Damage, and Fibrosis in Individuals Diagnosed with Human Immunodeficiency Virus and Pneumonia: A Cohort Study

“…IL-18 (interleukin-18) is a proinflammatory cytokine involved in the regulation of the immune response and inflammation [51][52][53]. Increased IL-18 levels have been observed in patients with HIV and pneumonia, suggesting an exacerbated inflammatory response [51,54,55]. IP10 (interferon gamma-inducible protein 10), also known as CXCL10, is a chemoattractive cytokine that attracts inflammatory cells, especially T lymphocytes, to the site of infection [56,57].…”