Background
HIV infection is associated with systemic immune activation. We longitudinally evaluated levels of circulation inflammatory biomarkers in youth with perinatal HIV (PHIV) and those perinatally HIV-exposed but uninfected (PHEU).
Methods
In a longitudinal sub-study of cardiac status among youth in the Pediatric HIV/AIDS Cohort Study, we measured 8 inflammatory biomarkers (Interleukin [IL]-1b, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-a [TNF-a], soluble TNF receptor 2 [sTNF-R2], and high-sensitive C-reactive protein [hsCRP]) at the start of the sub-study (T1) and ~11 years later (T2) among 99 PHIV and 59 PHEU participants with paired samples. At T1, the median age for PHIV was 13.0 years (64% female) and for PHEU, 11.2 years (56% female). Among PHIV, univariate and multivariate linear regression models were used to evaluate the associations of inflammatory biomarker levels at T2 with specific combination antiretroviral (cART) regimens, CD4 count, and viral load (VL).
Results
Among PHIV: 93% were receiving cART at T1 and 92% at T2; 72% had a viral load (VL) <400 copies/mL at T1 and 81% at T2; and 81% had a CD4 cell count > 500 cells/mm3 at T1 and 64% at T2. At T1, median levels were significantly higher among PHIV than PHEU for interleukin-18 (258 pg/mL, vs. 216 pg/mL, respectively) and TNF-a (8.3 pg/mL vs. 6.0 pg/mL). Among both groups, median levels of most biomarkers decreased between T1 and T2 except for TNF-a (increased in the PHEU group) and hsCRP (increased in both groups, see figure) There was a significantly greater decrease among PHIV than PHEU for IL-6, IL-8, IL-10, and TNF-a. At T2, only median TNF-a levels were significantly higher among PHIV than PHEU (1,880 pg/mL vs. 1,600 pg/mL). At T2: participants with a nadir CD4 <15% had 31% lower IL-8 levels (95% CI -60% to +17%) than those with nadir CD4%>25%; a CD4 count ≤500 was associated with 52% higher IL-18 levels (95% CI 11% to 110%); a VL ≥400 was associated with 91% higher sTNF-R2 levels (95% CI 22% to 200%); and integrase inhibitor use was associated with a 5%/year increase in IL-10 levels (95% CI 0.03% to 9.6%).
Conclusions
PHIV participants receiving cART and PHEU initially had similar levels of inflammatory biomarkers and most decreased over ~11 years in both groups. There was a significantly greater decrease among PHIV than PHEU for IL-6, IL-8, IL-10, and TNF-a. With cART, most levels in PHIV approached those of PHEU. Among PHIV, better control of HIV was associated with decreases in IL-18 and sTNF-R2 levels.
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