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