Identification of Three Immunologic Correlates for HIV Type 1 Pathogenesis in Youth

Abstract

To evaluate the stability and heterogeneity of cytokine and chemokine profiles in 80 youth with and without HIV-1 infection, we tested plasma samples at repeated visits without antiretroviral therapy. Among nine analytes that were quantified using multiplexing assays, interleukin 10 (IL-10), IL-18, and soluble CD30 persistently showed a positive correlation with HIV-1 viral load (Spearman r ¼ 0.40-0.59, p < 0.01 for all). A negative correlation with CD4 þ T cell counts (r ¼ À0.40 to À0.60, p < 0.01 for all) was also persistent for the three analytes. Analyses restricted to 48 AIDS-free youth (96 visits) yielded similar findings, as did multivariable models in which race, sex, age, body mass index, and time interval between visits were treated as covariates. These relationships reflected two novel features observed for all three analytes. First, their presence in plasma was relatively stable between visits (r ¼ 0.50-0.90, p < 0.03), regardless of HIV-1 infection status. Second, pairwise correlation was strong and persistent in HIV-1-seropositive youth (r ¼ 0.40-0.59, p < 0.01), but not in HIV-1, seronegatives ( p > 0.13). Additional analytes, especially eotaxin/CCL11 and SDF-1b/CXCL12, had no correlation with HIV-1-related outcomes despite their stability between visits. Overall, circulating IL-10, IL-18, and soluble CD30 could partially track unfavorable responses to HIV-1 infection in youth. These markers of persistent immune activation are individually and collectively indicative of HIV-1 pathogenesis.

Effect of MHC Haplotype on Immune Response upon Experimental SHIVSF162P4cy Infection of Mauritian Cynomolgus Macaques

“…Our data in macaques confirm the latter results obtained in humans, demonstrating a direct correlation between elevated plasma IL-10 levels and viral load during acute infection, concurrent with very high HIV viral load, which declined after the resolution of primary infection [33] . Moreover IL-10 levels correlated directly with HIV-1 viral load and inversely with CD4 counts, which is also consistent with previous evidence in humans [38] . Overall, the significant positive correlation of IFN- γ with IL-10 expression suggests that, as the production of pro-inflammatory cytokines increases, the production of IL-10 also increases to reduce inflammation and activation.…”

“…Moreover IL-10 levels correlated directly with HIV-1 viral load and inversely with CD4 counts, which is also consistent with previous evidence in humans [38]. Overall, the significant positive correlation of IFN- γ with IL-10 expression suggests that, as the production of pro-inflammatory cytokines increases, the production of IL-10 also increases to reduce inflammation and activation.…”

High Plasma Levels of sTNF-R1 and CCL11 Are Related to CD4+ T-Cells Fall in Human Immunodeficiency Virus Elite Controllers With a Sustained Virologic Control

“…It indicates that the influence of CCL11 on the risk of CD4 loss occurs also in other HIV-infected populations. However, it is important to note that other studies did not find any association between CCL11 and HIV disease progression (viral load and CD4 count) ( 26 ). CCL11 is a chemokine that selectively attracts lymphocytes through chemokine receptors (CCR3 and CCR5), which are also HIV co-receptors ( 27 ).…”

Cytokines Elevated in HIV Elite Controllers Reduce HIV ReplicationIn Vitroand Modulate HIV Restriction Factor Expression

“…IL-21 has also been shown to inversely correlate with viral load (40). IL-10, IL-18, and soluble CD30 (sCD30) correlated positively with viral load in a cohort of subjects with low viral load (Ͻ1,000 RNA copies/ml) and noncontrollers (41). Very few studies have examined systemic cytokine levels in ECs.…”