Background
Persistent antigen exposure may alter the development of the immune system in early life and inflammatory profiles may vary by geographic location and ethnicity. We have previously highlighted evidence of ongoing immune activation in youths with perinatally acquired HIV (YPHIV). We analyzed differences in inflammatory, chemokine and vascular biomarkers among YPHIV and seronegative (HIV-) youths in US and Uganda.
Methods
We measured plasma inflammatory biomarker levels in YPHIV and HIV- youths in the US (76) and Uganda (98) by ELISA and by the proinflammatory chemokine and vascular inflammation Legendplex panels. Biomarkers were compared using Wilcoxon rank-sum tests. Volcano plots were used to visualize differences in log-transformed fold changes (FC) of medians and their corresponding p-values between the two countries within each HIV status group.
Results
US participants were slightly younger (median age 14 yrs) than Ugandan participants (16 yrs) but were similar by sex (52% female). For YPHIV, median ART duration was 13.5 years, 100% of Ugandan and 87.5% of US YPHIV had HIV-1 RNA<50 c/mL. CMV antibodies were detected in 85% of Ugandans, and in 53% of US youth. Comparing markers by HIV status, we found that in Uganda, only d-dimer, and the chemokines CCL20 and CCL5 were higher in YPHIV compared to HIV-; in the US, however, several chemokines and inflammatory, gut, and vascular markers were higher in YPHIV compared to HIV-. We compared markers by site and found that levels of monocyte activation (sCD14) and vascular inflammation (ICAM, matrix metalloproteinase-9, osteopontin, serum amyloid A) were higher in US compared to Ugandan YPHIV; while markers of coagulation, lipid oxidation, systemic inflammation (d-dimer, IL6, OX LDL, TNFR II) and several chemokines (ENA-78, GROa, MIO_1a and MIP3a) all chemoattractant for neutrophils, monocytes and macrophages, were higher in Ugandan compared to US YPHIV. Several markers in each class were higher in Ugandan compared to US HIV- (see Figure).
Conclusions
There appears to be a significant role of country of residence on inflammatory and vascular biomarkers for youth with and without PHIV. The differences suggest both HIV-related factors (HIV viral clades) and non-HIV factors such as CMV status. Differences may also be due to social determinants of health, including dietary and psychosocial factors. Further studies on the lifelong consequences of HIV and environmental factors on inflammatory profiles are warranted.