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Incidence and predictors of cardiovascular disease, chronic kidney disease, and diabetes in HIV/HCV-coinfected patients who achieved sustained virological response


Data on the effects of sustained virologic response (SVR) to hepatitis C virus (HCV) therapy on the outcome of extrahepatic complications are scarce. We conducted this study to assess the impact of SVR on the occurrence of chronic kidney disease (CKD), diabetes mellitus (DM), and cardiovascular disease (CVD) in a cohort of human immunodeficiency virus (HIV)-infected patients. We analyzed coinfected HIV/HCV patients in the Management of Standardized Evaluation of Retroviral HIV Infection (MASTER) cohort. Only event-free patients with a serum HCV-RNA determination at baseline were included. Patients were divided into four groups: INF-exposed with SVR; INF-exposed without SVR; spontaneous HCV clearance; untreated viremic patients. We estimated the incidence of extrahepatic complications and employed Kaplan–Meier curves and Cox regression to assess the association of SVR/INF strata adjusted for a series of confounders. Data from 1676 patients were analyzed (20.29 % started an INF-based regimen). Overall, the incidence of CKD, DM, CVD, and death was 5.32 [95 % confidence interval (CI) 3.99–6.98], 10.13 (95 % CI 8.20–12.37), 6.79 (95 % CI 5.26–8.65), and 13.49 (95 % CI 11.29–16.0) per 1000 person-years of follow-up, respectively. In the Cox model for treated patients, SVR was not associated with a lower risk of CKD, DM, CVD, and death compared to non-SVR. Cirrhosis was significantly associated with a higher risk of CKD [hazard ratio (HR) 2.13; 95 % CI 1.06–4.31], DM (HR 3.48; 95 % CI 2.18–5.57), and death (HR 6.18; 95 % CI 4.1–9.31), but not of CVD (HR 1.14; 95 % CI 0.57–2.3). There are still many unknowns regarding the impact of SVR on the occurrence of extrahepatic complications in coinfected HIV/HCV patients. Further investigations are needed in order to elucidate the role of SVR as an independent prognostic factor for extrahepatic events.

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  1. Maggiolo F, Leone S (2010) Is HAART modifying the HIV epidemic? Lancet 376:492–493

    Article  PubMed  Google Scholar 

  2. Leone S, Gregis G, Quinzan G, Velenti D, Cologni G, Soavi L, Ravasio V, Ripamonti D, Suter F, Maggiolo F (2011) Causes of death and risk factors among HIV-infected persons in the HAART era: analysis of a large urban cohort. Infection 39:13–20

    CAS  Article  PubMed  Google Scholar 

  3. Mira JA, Rivero-Juárez A, López-Cortés LF, Girón-González JA, Téllez F, de los Santos-Gil I, Macías J, Merino D, Márquez M, Ríos-Villegas MJ, Gea I, Merchante N, Rivero A, Torres-Cornejo A, Pineda JA; Grupo Andaluz para el Estudio de las Hepatitis Víricas de la Sociedad Andaluza de Enfermedades Infecciosas (2013) Benefits from sustained virologic response to pegylated interferon plus ribavirin in HIV/hepatitis C virus-coinfected patients with compensated cirrhosis. Clin Infect Dis 56:1646–1653

    CAS  Article  PubMed  Google Scholar 

  4. Berenguer J, Alvarez-Pellicer J, Martín PM, López-Aldeguer J, Von-Wichmann MA, Quereda C, Mallolas J, Sanz J, Tural C, Bellón JM, González-García J; GESIDA3603/5607 Study Group (2009) Sustained virological response to interferon plus ribavirin reduces liver-related complications and mortality in patients coinfected with human immunodeficiency virus and hepatitis C virus. Hepatology 50:407–413

    CAS  Article  PubMed  Google Scholar 

  5. Berenguer J, Rodríguez E, Miralles P, Von Wichmann MA, López-Aldeguer J, Mallolas J, Galindo MJ, Van Den Eynde E, Téllez MJ, Quereda C, Jou A, Sanz J, Barros C, Santos I, Pulido F, Guardiola JM, Ortega E, Rubio R, Jusdado JJ, Montes ML, Gaspar G, Esteban H, Bellón JM, González-García J; GESIDA HIV/HCV Cohort Study Group (2012) Sustained virological response to interferon plus ribavirin reduces non-liver-related mortality in patients coinfected with HIV and Hepatitis C virus. Clin Infect Dis 55:728–736

    CAS  Article  PubMed  Google Scholar 

  6. Aleman S, Rahbin N, Weiland O, Davidsdottir L, Hedenstierna M, Rose N, Verbaan H, Stål P, Carlsson T, Norrgren H, Ekbom A, Granath F, Hultcrantz R (2013) A risk for hepatocellular carcinoma persists long-term after sustained virologic response in patients with hepatitis C-associated liver cirrhosis. Clin Infect Dis 57:230–236

    CAS  Article  PubMed  Google Scholar 

  7. Bedimo R, Westfall AO, Mugavero M, Drechsler H, Khanna N, Saag M (2010) Hepatitis C virus coinfection and the risk of cardiovascular disease among HIV-infected patients. HIV Med 11:462–468

    CAS  PubMed  Google Scholar 

  8. Butt AA, McGinnis K, Rodriguez-Barradas MC, Crystal S, Simberkoff M, Goetz MB, Leaf D, Justice AC; Veterans Aging Cohort Study (2009) HIV infection and the risk of diabetes mellitus. AIDS 23:1227–1234

    Article  PubMed  PubMed Central  Google Scholar 

  9. Peters L, Grint D, Lundgren JD, Rockstroh JK, Soriano V, Reiss P, Grzeszczuk A, Sambatakou H, Mocroft A, Kirk O; EuroSIDA in EuroCoord (2012) Hepatitis C virus viremia increases the incidence of chronic kidney disease in HIV-infected patients. AIDS 26:1917–1926

    CAS  Article  PubMed  Google Scholar 

  10. Torti C, Raffetti E, Donato F, Castelli F, Maggiolo F, Angarano G, Mazzotta F, Gori A, Sighinolfi L, Pan A, Cauda R, Scalzini A, Quiros-Roldan E, Nasta P, Gregis G, Benatti S, Digiambenedetto S, Ladisa N, Giralda M, Saracino A, Castelnuovo F, Di Pietro M, Lo Caputo S, Lapadula G, Costarelli S, Lorenzotti S, Mazzini N, Paraninfo G, Casari S, Focà E, Pezzoli C, Fabbiani M, Monno L, Pierotti P, Ble C, Leone S, Postorino MC, Fornabaio C, Zacchi F, Zoncada A, Carosi G (2015) Cohort profile: standardized management of antiretroviral therapy cohort (MASTER Cohort). Int J Epidemiol. 2015 Oct 7. pii: dyv192

  11. Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, Sulkowski SM, Torriani FJ, Dieterich DT, Thomas DL, Messinger D, Nelson M; APRICOT Clinical Investigators (2006) Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 43:1317–1325

    CAS  Article  PubMed  Google Scholar 

  12. Centers for Disease Control and Prevention (CDC) (1992) 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 41:1–19

    Google Scholar 

  13. Poynard T, McHutchison J, Davis GL, Esteban-Mur R, Goodman Z, Bedossa P, Albrecht J (2000) Impact of interferon alfa-2b and ribavirin on progression of liver fibrosis in patients with chronic hepatitis C. Hepatology 32:1131–1137

    CAS  Article  PubMed  Google Scholar 

  14. Shiratori Y, Imazeki F, Moriyama M, Yano M, Arakawa Y, Yokosuka O, Kuroki T, Nishiguchi S, Sata M, Yamada G, Fujiyama S, Yoshida H, Omata M (2000) Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med 132:517–524

    CAS  Article  PubMed  Google Scholar 

  15. Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, Ling MH, Albrecht J (2002) Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 122:1303–1313

    CAS  Article  PubMed  Google Scholar 

  16. Labarga P, Fernandez-Montero JV, Barreiro P, Pinilla J, Vispo E, de Mendoza C, Plaza Z, Soriano V (2014) Changes in liver fibrosis in HIV/HCV-coinfected patients following different outcomes with peginterferon plus ribavirin therapy. J Viral Hepat 21:475–479

    CAS  Article  PubMed  Google Scholar 

  17. Ginès P, Schrier RW (2009) Renal failure in cirrhosis. N Engl J Med 361:1279–1290

    Article  PubMed  Google Scholar 

  18. Ahmadieh H, Azar ST (2014) Liver disease and diabetes: association, pathophysiology, and management. Diabetes Res Clin Pract 104:53–62

    CAS  Article  PubMed  Google Scholar 

  19. Bruno R, Sacchi P, Puoti M, Maiocchi L, Patruno S, Carosi G, Filice G (2007) Natural history of compensated viral cirrhosis in a cohort of patients with HIV infection. J Acquir Immune Defic Syndr 46:297–303

    Article  PubMed  Google Scholar 

  20. Grint D, Peters L, Rockstroh JK, Rakmanova A, Trofimova T, Lacombe K, Karpov I, Galli M, Domingo P, Kirk O, Lundgren JD, Mocroft A; EuroSIDA in EuroCoord (2015) Liver-related death among HIV/hepatitis C virus-co-infected individuals: implications for the era of directly acting antivirals. AIDS 29:1205–1215

    CAS  Article  PubMed  Google Scholar 

  21. Mocroft A, Ryom L, Begovac J, Monforte AD, Vassilenko A, Gatell J, Florence E, Ormaasen V, Kirk O, Lundgren JD; EuroSIDA in EuroCOORD (2014) Deteriorating renal function and clinical outcomes in HIV-positive persons. AIDS 28:727–737

    Article  PubMed  Google Scholar 

  22. Choi AI, Li Y, Deeks SG, Grunfeld C, Volberding PA, Shlipak MG (2010) Association between kidney function and albuminuria with cardiovascular events in HIV-infected persons. Circulation 121:651–658

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Bandera A, Gori A, Sabbatini F, Madeddu G, Bonora S, Libertone R, Mastroianni C, Bonfanti P, d’Arminio Monforte A, Cozzi-Lepri A; Icona Foundation Study Group (2015) Evaluation of the prognostic value of impaired renal function on clinical progression in a large cohort of HIV-infected people seen for care in Italy. PLoS One 10:e0124252

    Article  PubMed  PubMed Central  Google Scholar 

  24. Mehta SH, Brancati FL, Sulkowski MS, Strathdee SA, Szklo M, Thomas DL (2000) Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States. Ann Intern Med 133:592–599

    CAS  Article  PubMed  Google Scholar 

  25. Mehta SH, Brancati FL, Strathdee SA, Pankow JS, Netski D, Coresh J, Szklo M, Thomas DL (2003) Hepatitis C virus infection and incident type 2 diabetes. Hepatology 38:50–56

    Article  PubMed  Google Scholar 

  26. Butt AA, Fultz SL, Kwoh CK, Kelley D, Skanderson M, Justice AC (2004) Risk of diabetes in HIV infected veterans pre- and post-HAART and the role of HCV coinfection. Hepatology 40:115–119

    Article  PubMed  Google Scholar 

  27. Data Collection on Adverse Events of Anti-HIV drugs (D:A:D) Study Group, Smith C, Sabin CA, Lundgren JD, Thiebaut R, Weber R, Law M, Monforte Ad, Kirk O, Friis-Moller N, Phillips A, Reiss P, El Sadr W, Pradier C, Worm SW (2010) Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D Study. AIDS 24:1537–1548

    Google Scholar 

  28. Elkrief L, Chouinard P, Bendersky N, Hajage D, Larroque B, Babany G, Kutala B, Francoz C, Boyer N, Moreau R, Durand F, Marcellin P, Rautou PE, Valla D (2014) Diabetes mellitus is an independent prognostic factor for major liver-related outcomes in patients with cirrhosis and chronic hepatitis C. Hepatology 60:823–831

    CAS  Article  PubMed  Google Scholar 

  29. Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, Kowalska JD, de Wit S, Law M, el Sadr W, Kirk O, Friis-Moller N, Monforte Ad, Phillips AN, Sabin CA, Lundgren JD; D:A:D Study Group (2014) Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet 384:241–248

    Article  PubMed  Google Scholar 

  30. Petta S, Macaluso FS, Craxì A (2014) Cardiovascular diseases and HCV infection: a simple association or more? Gut 63:369–375

    Article  PubMed  Google Scholar 

  31. Chew KW, Hua L, Bhattacharya D, Butt AA, Bornfleth L, Chung RT, Andersen JW, Currier JS (2014) The effect of hepatitis C virologic clearance on cardiovascular disease biomarkers in human immunodeficiency virus/hepatitis C virus coinfection. Open Forum Infect Dis 1:ofu104

    Article  PubMed  PubMed Central  Google Scholar 

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The MASTER study is sponsored by the M.I.S.I. Foundation (Fondazione Malattie Infettive e Salute Internazionale, We would like to thank all patients participating in the MASTER cohort study, all doctors and study nurses involved, and the data center. We would also like to thank ANLAIDS (National Association against AIDS), Sezione Lombardia for its continuous support of our work. Preliminary results of this study were presented at the 22nd Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, WA, 23–26 February 2015, abstract number 655.

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Correspondence to S. Leone.

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Conflict of interest

SL received speaker grants from Janssen-Cilag, Pfizer, and travel grants from Gilead, Janssen-Cilag, Pfizer. SC received speaker grants from Abbvie, BMS, Gilead, MSD, Viiv, and travel grants from BMS, Gilead, ViiV, is a member of the advisory boards of Abbvie, scientific debrief for Gilead, employee of Gilead from August 2012 to July 2013; PN received speaker grants and advisory board honoraria from BMS, MSD, Viiv; AS received payment for the development of educational presentations from BMS, Gilead, MSD, ViiV; MDP received speaker grants from Abbvie, BMS, Gilead, MSD, Viiv, is a member of the advisory boards of Abbvie; AG received grants/research supports from Abbvie, Astellas, BMS, Boehringer, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, ViiV, ANLAIDS Sezione Lombarda, honoraria or consultation fees from BMS, Gilead, Janssen, MSD, Novartis, ViiV, travel grant/supports from BMS, Gilead, Jansen, ViiV, and participation in a company-sponsored speakers’ bureau of Gilead. The other authors declare no conflict of interests.

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Each site obtained approval by a local Ethics Committee.

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Informed consent was obtained from all individual participants included in the study.

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Leone, S., Prosperi, M., Costarelli, S. et al. Incidence and predictors of cardiovascular disease, chronic kidney disease, and diabetes in HIV/HCV-coinfected patients who achieved sustained virological response. Eur J Clin Microbiol Infect Dis 35, 1511–1520 (2016).

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  • Human Immunodeficiency Virus
  • Chronic Kidney Disease
  • Sustained Virologic Response
  • Body Mass Index Group
  • Normal Body Mass Index Group