Open AccessDeterminants of IL‐6 levels during HIV infection
Author(s) -
Borges Álvaro H,
O'Connor Jemma L,
Phillips Andrew N,
Rönsholt Frederikke F,
Pett Sarah,
Vjecha Michael J,
French Martyn A,
Lundgren Jens D
Publication year - 2014
Publication title -
journal of the international aids society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.724
H-Index - 62
ISSN - 1758-2652
DOI - 10.7448/ias.17.4.19482
Subject(s) - medicine , population , diabetes mellitus , hepatitis c , human immunodeficiency virus (hiv) , multivariate analysis , demographics , hepatitis b , gastroenterology , immunology , demography , endocrinology , environmental health , sociology
Elevated IL‐6 levels have been linked to increased risk of cardiovascular disease (CVD), cancer and death. Compared to the general population, treated HIV+ persons have 50–100% higher IL‐6 levels, but few data on the determinants of IL‐6 levels during HIV infection currently exist. Material and Methods Participants in three international HIV trials (SMART, ESPRIT and SILCAAT) with IL‐6 plasma levels measured at baseline were included ( N =9864). Factors independently associated with log2‐transformed IL‐6 level were identified by multivariate linear regression; exponentiated estimates corresponding to fold differences (FDs) in IL‐6 were calculated. Demographics (age, gender, race, BMI) and HIV‐specific variables (nadir and entry CD4 counts, HIV‐RNA, use of different ART regimens) were investigated in all three trials. In SMART ( N =4498), smoking, comorbidities (CVD, diabetes, hepatitis B/C [HBV/HCV]), HDL‐cholesterol, renal function (eGFR) and educational level were also assessed. Results Demographics associated with higher IL‐6 were older age (FD [95% CI]: 1.09 [1.08–1.11] per 10 yr) and higher BMI (1.02 [1.01–1.04] per 5 kg/m 2 ), whereas black race was associated with reduced IL‐6 (0.96 [0.93–0.99]). As for HIV variables, patients not receiving ART (1.36 [1.29–1.43]) and with higher HIV‐RNA (1.24 [1.01–1.52] for >100,000 vs. ≤500 copies/mL) had increased IL‐6. Participants taking protease inhibitors (PI) had higher IL‐6 (1.14[1.09–1.19]). Higher nadir CD4 count (0.98 [0.97–0.99]/100 cells/µL) was related to lower IL‐6. All evaluated comorbidities were related to higher IL‐6; FDs in IL‐6 were 1.08 [1.04–1.12] for smoking, 1.12 [1.02–1.24] for CVD, 1.07 [1.00–1.16] for diabetes and 1.12 [1.02–1.24] for HBV (1.15 [1.02–1.30]) and 1.53 [1.45–1.62] for HCV. IL‐6 increased with decreasing eGFR (0.98 [0.97–1.00]/10 mL/min) and HDL‐cholesterol (0.98 [0.96–0.99]/10 mg/mL). Lower education was related to higher IL‐6 (1.09 [1.03–1.15] for high school vs. bachelor's degree). Conclusions Higher IL‐6 levels were associated with older age and non‐black race, higher BMI and lower HDL‐cholesterol, ongoing HIV replication, low nadir CD4 counts, comorbidities and decreased renal function. This suggests that there are multiple causes of inflammation in treated HIV infection. A possible contribution from PI use was also observed. Contribution from inflammation to explain variation in clinical outcomes for these factors should be investigated.