Poster Sessions # P-C7, TD-C Abstract # 303,303 22th Conference on Retroviruses and Opportunistic Infections February 23- 26, 2015 Seattle, WA, USA sCD163 increase in HIV/CMV coinfected subjects included in ICONA Cohort Serena Vita1, Miriam Lichtner2, Giulia Marchetti3, Claudia Mascia1, Esther Merlini3, Paola Cicconi3, Vincenzo Vullo1, Pier Luigi Viale4, Alberto Costantini5, Antonella d'Arminio Monforte2 for ICONA Foundation Study Group 1University Serena Vita, MD PhD University of Rome Sapienza Viale del Policlinico, 133 00185 Rome, Italy E-mail: [email protected] of Rome Sapienza, Rome, Italy, 2University of Rome Sapienza, Polo Pontino, Latina, Italy, 3San Paolo Hospital, Milano, Italy, 4University of Ancona, Ancona, Italy, 5University of Bologna, Bologna, Italy. Results Background Accumulating evidence suggest that inflammatory cytokines produced by monocytes/macrophages play a role in the vascular disease and cognitive decline. In HIV patients, herpes virus coinfection has been proposed as a key factor in sustaining immune activation, even in presence of HIV plasma viral control. In our previous study on the ICONA cohort we showed that in HIV patients (pts), CMV infection is an independent risk factor for non AIDS events/deaths (fig. 1). Time to NON AIDS EVENT/DEATH Percent survival 100 CMVIgG_POSITIVE CMVIgG_NEGATIVE 90 80 70 0 5 10 15 20 Years Fig. 1 shows the increased rate of incurring in SNA event/NA death. Lichtner et al., 2014. A total of 69 subjects were recruited, 46 HIV monoinfected (CMV-) and 23 HIV/CMV (CMV+) coinfected. A higher median of sCD163 level (927.7 vs. 497.8 ng/ml, p=0.018) was found in CMV+ compared to CMV- group (fig.2 A). TNFα, sCD14 were also elevated but did not reach a significant difference in comparison to HIV/CMV- subjects (fig. 3). In HIV/CMV+ subjects a significant correlation was shown between anti-CMV IgG levels and sCD163 (r=0.49, p=0.006) (fig.2 B). Moreover only in CMV+ subjects sCD163 levels were related to the duration of HIV infection (r=0.29, p=0.04). In the CMV positive group comparing CMV IgG levels with CD4 count, at the time of sampling, we found a significant negative correlation (r=0.39, p=0.0006). Aims • To study the differences in plasma markers of myeloid immune activation, related to cardiocerebro vascular diseases in HIV monoinfected and HIV/CMV coinfected pts, • To correlate CMV IgG levels in HIV/CMV+ with soluble activation markers. Study population Screening of all the ICONA patients with an available CMV serology at enrolment (or within 6 months) and a plasma sample after >1 year of successful ART (defined as an undetectable HIV viral load and CD4+ count more than 200/mc). Matching criteria HIV/CMV(23 pts) HIV/CMV+ (46 pts) Sex 2F, 21M 4F, 42M Age (Mdn, min-max) 40 (34-52) 42 (31-54) CD4 nadir (mm3, Mdn, min-max) 281 (2-598) 207 (2-611) HBV 0 0 HCV 7 14 Tab. 1 shows the matching criteria of the 2 groups. Among these patients 2 different groups have been constituted: CMV-infected and CMVuninfected patients. CMV chronic infection was defined on CMV IgG presence. We selected HIV CMV+ and CMV- patients with a plasma sample after 1 year or more of successful therapy, matched for sex, age, CD4 nadir, HBV and HCV (see table 1). Exclusion criteria Previous or current CMV organ diseases, organ transplantation, use of immunosuppressive or immunomodulant drugs in the last year, cancer or treatment for cancer in the previous 5 years, insulin dependent diabetes mellitus, glomerular filtration rate < 39 ml/min, severe liver disease, endocrine disorders, autoimmune disease. Fig. 2A shows sCD163 levels in HIV/CMV- vs. HIV/CMV+. 2B shows correlation between CMV IgG levels with sCD163. Fig. 3 shows TNFα and sCD14 levels in HIV/CMV- vs. HIV/CMV+. Conclusions CMV chronic infection appears to be linked to an increase in sCD163, a markers of myeloid activation, in HIV infected subjects under successful ART with controlled biological (age and sex) and HIV related (HIV suppression, CD4 nadir and CD4 recovery) factors. The persistent activation of monocytes and macrophages that has been implicated in the accelerated development of vascular and neurological disease in general population, may explain the increased risk of non AIDS events found in HIV/CMV coinfected subjects. Materials and methods Immunological Assays Plasma levels in duplicate of : IL-6 and TNFα: (pg/ml) eBIOSCENCE, sCD163 and sCD14(ng/ml) R&D Systems CMV ELISA Quantitation Kit: GenWay Biotech used to retest all samples and in the CMV positive populations to quantify Ab levels in duplicate. Statistical analysis Mann-Withney Test, Spearman correlation analysis (Prima 6.0 software) Board of Directors: M. Moroni (Chair), M. Andreoni, G. Angarano, A. Antinori, A. d’Arminio Monforte, F. Castelli, R. Cauda, G. Di Perri, M. Galli, R. Iardino, G. Ippolito, A. Lazzarin, C.F. Perno, F. von Schlösser, P.L. Viale Presidential : A. Cozzi-Lepri, P. Cicconi, I. Fanti, T. Formenti, L. Galli, P. Lorenzini Biological Bank INMI : F.Carletti, S. Carrara, A. Castrogiovanni, A. Di Caro, F. Petrone, G. Prota, S. Quartui Participating Physicians and Centers Ancona - A. Giacometti, S. Mazzoccato, E. Orsetti; Bari - G. Angarano, L. Monno, C. Santoro; Bergamo - F. Maggiolo, C. Suardi; Bologna - M. Borderi, V. Donati, E. Vanino, G. Verucchi, P. Viale; Brescia - F. Castelli, C. Minardi, E. Quiros Roldan; Busto Arsizio - C. Abeli, T. Quirino; Catania - G. Nunnari, B. Celesia; Chieti - K. Falasca, J. Vecchiet; Ferrara - D. Segala, L. Sighinolfi; Firenze - F. Mazzotta, S. Lo Caputo; Genova - A.I. Alessandrini, N. Bobbio, G. Cassola, G. Mazzarello, R. Piscopo, C. Viscoli; Lecco - P. Bonfanti, I. Caramma; Macerata - P. Castelli, A. Chiodera; Milano - L. Carenzi, A. Castagna, P. Cicconi, A. d'Arminio Monforte, M. Galli, A. Lazzarin, G. Marchetti, M.C. Moioli, R. Piolini, M. Puoti, A. Ridolfo, G. Rizzardini, S. Salpietro; Modena - C. Mussini, C. Puzzolante Monza - A. Gori, G. Lapadula; Napoli - N. Abrescia, A. Chirianni, M. Gargiulo, A. Maddaloni; Perugia - F. Baldelli, D. Francisci; Pescara - G. Parruti, T. Ursini; Reggio Emilia - G. Magnani, M. Ursitti; Roma - R. Acinapura, A. Ammassari, M. Andreoni, A. Antinori, M. Capozzi, R. Cauda, A. Cingolani, A. d'Avino, A. De Luca, L. Gallo, R. Libertone, C. Mastroianni, E. Nicastri, G. Tebano, V. Vullo; Rovigo - A.M. Cattelan; Sassari - G. Madeddu, P.E. Manconi, M.S. Mura, P. Piano; Siena - A. De Luca, B. Rossetti; Siracusa - R. Fontana Del Vecchio, A. Franco; Torino - S. Bonora, P. Caramello, G. Di Perri, G. Orofino, M. Sciandra; Udine - M. Bassetti, A. Londero; Vicenza - V. Manfrin, G. Pellizzer; Commitee : A. Antinori, A. d’Arminio Monforte, A. Lazzarin, M. Moroni, G. Ippolito, C.F. Perno Scientific Secretary: A. d’Arminio Monforte (Coordinator), A. Antinori, A. Castagna, F. Ceccherini-Silberstein, A. Cozzi-Lepri, E. Girardi, S. Lo Caputo, C. Mussini, M. Puoti Scientific Committee: A. Ammassari, M. Andreoni, A. Antinori, A. d’Arminio Monforte, C. Balotta, P. Bonfanti, S. Bonora, M. Borderi, M.R. Capobianchi, A. Castagna, F. Ceccherini-Silberstein, A. Cingolani, P. Cinque, A. Cozzi-Lepri, A. De Luca, A. Di Biagio, N. Gianotti, E. Girardi, A. Gori, G. Guaraldi, G. Lapadula, M. Lichtner, S. Lo Caputo, G. Madeddu, F. Maggiolo, G. Marchetti, S. Marcotullio, L. Monno, C. Mussini, M. Puoti, E. Quiros Roldan, S. Rusconi
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