Active HCV Replication but Not HCV or CMV Seropositive Status Is Associated with Incident and Prevalent Type 2 Diabetes in Persons Living with HIV

De Luca, A.; Lorenzini, P.; Castagna, A.; Puoti, M.; Gianotti, N.; Castelli, F.; Mastroianni, C.; Maggiolo, F.; Antinori, A.; Guaraldi, G.; Lichtner, M.; D'Arminio Monforte, A.; Andreoni, M.; Angarano, G.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; Von Schloesser, F.; Viale, P.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Ammassari, A.; Balotta, C.; Bandera, A.; Bonfanti, P.; Bonora, S.; Borderi, M.; Calcagno, A.; Calza, L.; Capobianchi, M. R.; Cingolani, A.; Cinque, P.; Di Biagio, A.; Gori, A.; Lapadula, G.; Madeddu, G.; Marchetti, G.; Marcotullio, S.; Monno, L.; Nozza, S.; Quiros Roldan, E.; Rossotti, R.; Rusconi, S.; Santoro, M. M.; Saracino, A.; Zaccarelli, M.; Fanti, I.; Galli, L.; Rodano, A.; Shanyinde, M.; Tavelli, A.; Carletti, F.; Carrara, S.; Di Caro, A.; Graziano, S.; Petrone, F.; Prota, G.; Quartu, S.; Truffa, S.; Giacometti, A.; Costantini, A.; Valeriani, C.; Santoro, C.; Suardi, C.; Donati, V.; Verucchi, G.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Cacopardo, B.; Celesia, B.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Vichi, F.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Bobbio, N.; Mazzarello, G.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, A. P.; Rizzardini, G.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Puzzolante, C.; Abrescia, N.; Chirianni, A.; Borgia, G.; Di Martino, F.; Maddaloni, L.; Gentile, I.; Orlando, R.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Vullo, V.; Cristaudo, A.; Baldin, G.; Cicalini, S.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Savinelli, S.; Latini, A.; Iaiani, G.; Fontanelli Sulekova, L.; Cecchetto, M.; Viviani, F.; Mura, M. S.; Rossetti, B.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.

doi:10.1097/QAI.0000000000001443

Objective: To analyze the association between chronic hepatitis C virus (HCV) and cytomegalovirus (CMV) infections with type 2 diabetes in HIV-infected patients. Methods: HIV-1-infected patients enrolled in ICONA, a prospective cohort study involving 42 tertiary care centers in Italy, were selected with the following characteristics: for the diabetes incidence analysis, all patients with available CMV IgG results (first available test = baseline) and without type 2 diabetes were followed until onset of type 2 diabetes, last available clinical follow-up, death or September 30, 2014, whichever occurred first; for the prevalence analysis, all ICONA patients were analyzed at their last follow-up visit. Main outcome measures were the new onset of type 2 diabetes (incidence analysis) and the prevalence of type 2 diabetes at last follow-up. Results: During 38,062 person-years of follow-up (PYFU) in 6505 individuals, we observed 140 cases of incident type 2 diabetes (Incidence rate 3.7, 95% CI: 3.1 to 4.3, per 1000 PYFU). In a multivariable Poisson regression model, HCV-antibody (Ab)+/HCV RNA+ patients [adjusted relative rate versus HCV-Ab negative 1.73 (95% CI: 1.08 to 2.78)] but not HCV Ab+RNA- or CMV IgG+ patients, had a higher risk of diabetes. Among 12,001 patients, 306 (2.5%) prevalent cases of type 2 diabetes were detected. HCV Ab+RNA+ status was independently associated with prevalent diabetes (adjusted Odds Ratio vs HCV Ab- 2.49; 95% CI: 1.08 to 5.74), whereas HCV-Ab+/HCV RNA- and CMV IgG+ status were not. Conclusion: In HIV-infected individuals, active HCV replication but not prior HCV exposure or latent CMV infection is associated with incident and prevalent type 2 diabetes.