CROI 2020 Abstract eBook
network in individuals longitudinally sampled before they began antiretroviral therapy (ART) and after achieving suppression of HIV RNA. Methods: Concentrations of 34 cytokine/chemokines were measured by multiplex-bead assay in longitudinal blood and seminal plasma from 20 men with HIV from a well-studied cohort with banked blood and seminal samples when viremic and suppressed. We used Partial Least Squares Discriminant Analysis (PLS-DA) to visualize the difference in cytokine pattern between the time points and rank the relative importance of cytokines for determining suppression status. Any cytokines with Variable Importance on PLS Projections (VIP) scores exceeding 1 were deemed important in predicting suppression status and were subsequently tested using Wilcoxon Signed Rank Tests. Results: Baseline characteristics of our cohort included median age of 33 years (IQR 27-41), median CD4+ T cell count 702/µL (range 324-997), and median pre-ART HIV viral loads in blood log 10 4.7 (range 2.8-6.6). Significant overlap of the PLS-DA projections in blood suggested no significant difference in the overall cytokine network after suppression of viremia, even though individual cytokines changed in line with published findings from other studies. However, the projections are significantly different in seminal plasma, highlighting the importance of immune activation in this compartment. When tested individually, four cytokines were significantly different across time points in semen (MIG, IL-15, and IL-7: all p < 0.001; ITAC: p = 0.019), while only two were significantly different across time points in blood (MIG and IP-10, both p = 0.006). Conclusion: Our study demonstrates that viral suppression with ART has the most significant decrease in the inflammatory milieu in seminal plasma, while the overall effect on the network of cytokines in the blood is weaker. These results identify specific changes in the cytokine networks in semen and blood—consistent with prior reports—as the immune system acclimates to chronic, suppressed HIV infection and they highlight the utility of novel statistical methods in the analysis of large data sets of cytokine measurements.
mediated inflammation in PWH is unclear. We analysed differences in markers of inflammation and immune activation in obese and non-obese PWH. Methods: We recruited PWH with and without obesity (BMI>30 kg/m 2 ) from the UCD ID Cohort, a multicentre prospective cohort, in a ratio of 1:2, obese versus non-obese, matched for age, gender and ethnicity. In a bead-based, multiplex, quantitative ELISA we measured 25 plasma biomarkers covering pathways related to systemic inflammation (hsCRP, IL-2, IL-6, TNFR1, TNFR2, TNF-α, IL-1β), coagulation (vWF, D-dimer, sCD40L), endothelial function (E-selectin, P-selectin, sICAM-1, VCAM), atherosclerosis (MPO, Lp-PLA2), immune regulation (IL-4, IL-1RA), innate immune activation (MIP-1, MCP-1, sCD163, sCD14) and microbial translocation (IL-18, LBP). We explored associations between biomarkers and obesity using logistic regression adjusted for age, gender, ethnicity, smoking status, NRTI backbone and use of INSTI. Data are median [IQR] or odds ratio (OR) [95% CI] Results: We included 99 PWH on ART, 33 obese (BMI 33.6;[30.7, 45.5] Kg/m 2 ), age 41 [36, 48] years; 45% African with 54% and 56%men in the obese and non-obese groups. Overall 63%were heterosexual, 18%MSM and 8% IDU; 94% had HIV-RNA <40 cps/mL. Use of INSTI was 57% vs 38%, and TAF 36% vs 33% in obese and non-obese. 9 markers were significantly associated with obesity in adjusted analyses: hsCRP (OR 2.1, [1.4,3.1]), IL-6 (2.18, [1.2,4.1]), TNF-α (3.9, [1.3,11.6]), TNFR2 (2.19, [1.0,4.7]), vWF (4.64, [4.6,14.5]), E-selectin (5.52, [1.3,23.6]), MPO (3.95, [1.3,12.0]), IL-4 (1.04, [1.0,1.1]), IL-1RA (6.31, [2.4,16.5]). Obese phenotype was characterised by increases in markers of systemic inflammation, coagulation and endothelial function rather than innate immune activation or microbial translocation (Fig 1) Conclusion: In the first study of biological patterns of inflammation in obese PWH, obese phenotype was associated with increases in systemic inflammatory, vascular and coagulation pathways, rather than in innate immune activation or microbial translocation, previously associated with HIV infection. Whether these distinct patterns of inflammation contribute to greater risk of comorbidities in obese PWH remains to be determined
222 RESIDUAL IMMUNE ACTIVATION IN AFRICANS ON ART PREDICTS CD4 RECOVERY AND VIRAL REBOUND Stefanie Kroeze 1 , Theresa M Rossouw 2 , Helen Steel 2 , Ferdinand Wit 1 , Cissy Kityo 3 , Margaret Siwale 4 , Sulaimon Akanmu 5 , Kishorchandra Mandaliya 6 , Marleen de Jager 7 , Pascale Ondoa 1 , Peter Reiss 1 , Tobias F. Rinke de Wit 1 , Neeltje A. Kootstra 8 , Raph L. Hamers 1 , for the PanAfrican Studies to Evaluate Resistance (PASER) 1 Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands, 2 University of Pretoria, Pretoria, South Africa, 3 Joint Clinical Research Centre, Kampala, Uganda, 4 Lusaka Trust Hospital, Lusaka, Zambia, 5 University of Lagos, Lagos, Nigeria, 6 University of Nairobi, Nairobi, Kenya, 7 Muelmed Hospital, Pretoria, South Africa, 8 Academic Medical Center, Amsterdam, Netherlands
221 MARKERS OF IMMUNE ACTIVATION AND FUNCTION IN OBESE AND NONOBESE SUBJECTS WITH HIV Stefano Savinelli 1 , Emma Haran 1 , Padraig McGettrick 1 , Alejandro A. Garcia 1 , Willard Tinago 1 , Elena Alvarez-Barco 1 , Eoin Feeney 1 , Alan Landay 2 , Patrick W. Mallon 1 1 University College Dublin, Dublin, Ireland, 2 Rush University Medical Center, Chicago, IL, USA Background: Obesity is an emerging health issue in people with HIV (PWH). Both obesity and HIV are associated with systemic inflammation contributing to metabolic and cardiovascular complications. How obesity impacts on immune-
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