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ORAL CYTOKINE EXPRESSION IS LINKED TO ORAL HIV-1 LEVELS IN ACTG A5254
Joseph Rocco1, Zachary York2, Janet McLaughlin1, Luann Borowski1, Jennifer Webster-Cyriaque3, Caroline H. Shiboski4, Judith Aberg5, Charles Rinaldo1, Bernard J. Macatangay1
1University of Pittsburgh, Pittsburgh, PA, USA,2University of Wisconsin–Madison, Madison, WI, USA,3University of North Carolina at Chapel Hill, Chapel Hill, NC, USA,4University of California San Francisco, San Francisco, CA, USA,5Icahn School of Medicine at Mt Sinai, New York, NY, USA
HIV infection is known to disrupt oral mucosal immunity, but the pathogenesis of this immune dysregulation remains unknown. We determined the levels of 11 soluble immune mediators in oral washings of people with HIV (PWH) with varying levels of plasma viremia and CD4+ T cell counts. We also evaluated whether these immune mediators are associated with levels of HIV in blood and oral washings with the aim of characterizing the mucosal immune response at variable stages of HIV infection.
Oral washings were obtained from participants of ACTG A5254, a cross-sectional study of PWH to evaluate oral complications of HIV. Participants were divided into 4 strata: A (n=148; 52% on ART), CD4≤200 cells/mm3, plasma HIV-1 RNA (VL)>1000 cps/mL; B (n=82; 98% on ART), CD4≤200, VL≤1,000; C (n=29; 21% on ART), CD4>200, VL>1000; D (n=29; 100% on ART), CD4>200, VL≤1000. Levels of soluble markers were tested in oral washings using a multi-bead fluorescent platform, and were compared between strata. Associations between soluble marker levels and HIV in plasma and oral washings as well as CD4+ counts were determined.
Stratum (St) A participants (CD4 <200, VL >1000) had higher levels of pro-inflammatory markers IL-6, IL-17, TNFα, IL-1β, and IFNγ compared to St B and St D which had VL<1000 and where 98-100% of participants were on ART (p=0.02 to p<0.0001; Kruskal-Wallis with Dunn's post-test, adjusted for multiple comparisons), but were not different from St C. Two pro-inflammatory markers, IL-12p70 and IL-8, and the anti-inflammatory marker IL-10 differentiated St A from the other 3 strata (p=0.046 to p<0.0001). St B and D had no differences in levels of the soluble markers except for IFNγ (p=0.04). Oral HIV levels correlated with plasma HIV (r=0.76; p<0.0001, Spearman) and with IL-6, IL-1β, IL-8, TNFα, IFNγ, and IL-10 (all r>0.4; p<0.001). Meanwhile, plasma VL only correlated with TNFα, IFNγ, and IL-10 (all r>0.4; p<0.001). No correlations were seen with IL-2, and only modest (r<0.35) correlations were seen with IL-17. No significant correlations were observed with CD4 count.
Our results suggest that high levels of oral HIV rather than low CD4 counts or plasma HIV are more linked to production of oral immune mediators. Despite severe immunosuppression, participants with AIDS demonstrated elevated levels of cytokines corresponding to both Th1 and Th2 T cell responses. The interplay of HIV and these immune mediators could be an important factor in the oral health of PWH.