LIVER-RELATED ADVERSE EVENTS WITH DARUNAVIR-BASED ANTIRETROVIRAL TREATMENT IN HIV/HCV INFECTED PATIENTS

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1 ICAR 2013 Italian Conference on AIDS and Retrovirus LIVER-RELATED ADVERSE EVENTS WITH DARUNAVIR-BASED ANTIRETROVIRAL TREATMENT IN HIV/HCV INFECTED PATIENTS Antonio Di Biagio, Laura Nicolini, Patrizia Lorenzini, Massimo Puoti, Andrea Antinori, Alessandro Cozzi-Lepri, Andrea Gori, Jacopo Vecchiet, Cristina Mussini, Massimo Andreoni, Claudio Viscoli, Antonella d Arminio Monforte for the Icona Foundation Study Group

2 Background

3 Background [2] HCV-positive patients in DRV arm, n (%) POWER1 31 (12) 1 POWER2 0 (0) POWER3 52 (16) 1,2 TITAN ND ARTEMIS 43 (13) 1 1 Not requiring treatment during the trial period 2 HBsAb-positive or HCV RNA positive in 45 (14%) cases 3 Defined as HCV-Ab positivity, HCV viremia not sistematically collected

4 Objective To analyze the incidence of liver related events in HCV/HIV co-infected patients during DRV/r based ART.

5 PATIENTS AND METHODS HIV-infected patients enrolled in the ICONA Foundation Study receiving DRV/r based ART Exclusion criteria: HBsAg-positive patient Lack of liver enzyme determination at baseline and/or follow up Chronic HCV infection defined as HCV-Ab positivity Liver enzyme elevations (LEE) from baseline categorized using international standardized toxicity grade scale. The incidence rate ratios (IRR) of LEE were compared between HCV-Ab positive and negative patient in intention-to-treat (ITT until the last follow up after DRV discontinuation) and on-treatment (OT up to DRV discontinuation) analysis.

6 STUDY POPULATION 872 patients treated with DRV/r 232 (28%) HCV serology missing 59 (5%) liver enzymes missing 18 (2%) excluded for HBsAg+ in the absence of HCVAb+ 563 patients enrolled 314 (55.8%) ART-naïve 443 (78.7%) males 41 years old (IQR 35-49) 2.1 years from HIV infection (median, IQR ) 343/mmc CD4+ T cell count (median, IQR ) 432 (77%) HCV Ab- 131 (23%) HCVAb+

7 RESULTS ANALISI ITT ANALISI OT HCV+ IR LEE 11.8/100 PYFU 95%CI HCV- IR LEE 13.1/100 PYFU 95%CI P=0.690 HCV+ IR LEE 14.4/100 PYFU 95%CI HCV- IR LEE 9.4/100 PYFU 95%CI p= Kaplan-Meier failure estimates analysis time Number at risk hcv = N hcv = Y hcv = N hcv = Y Kaplan-Meier failure estimates analysis time Number at risk hcv = N hcv = Y hcv = N hcv = Y HCV pos HCV neg 1-year probability of liver toxicity 17,3% 7,5% 2-years probability of liver toxicity 22,4% 17,9% HCV pos HCV neg 1-year probability of liver toxicity 18,9% 7,0% 2-years probability of liver toxicity 22,4% 13,3%

8 RESULTS 2 LIVER TOXICITY EVENT HCV+ (n 132) HCV- (n 432) Grade 1 16 (84.2%) 52 (88.1%) Grade 2 3 (15.8%) 5 (8.5%) Grade (1.7%) Grade (1.7%) ITT analysis OT analysis IRR 95% CI p IRR 95% CI p HCV-positive serostatus 1,89 0,90 3,96 0,092 2,13 0,95 4,81 0,068 ALT at DRV/r initiation 0,97 0,95 0,99 0,000 0,96 0,94 0,98 0,000 Previously naive patients 2,09 1,11 3,91 0,022 1,76 0,82 3,79 0,150 Male gender 1,97 1,00 3,88 0,050 1,98 0,88 4,43 0,097 T CD4+ at DRV/r initiation, 100 cells higher 0,91 0,81 1,02 0,123 0,79 0,67 0,93 0,004

9 Naive patients ITT analysis IRR 95% CI p HCV-positive serostatus 6,86 1,46 32,18 0,015 ALT at DRV/r initiation 0,90 0,82 0,99 0,024 Male gender 3,10 0,40 23,74 0, Kaplan-Meier failure estimates analysis time Number at risk hcv = N hcv = Y hcv = N hcv = Y

10 Conclusions Mild to moderate LEE were no more frequent in HCV+/HIV+ patients than in HCV-/HIV+ No severe LEE were recorded in HCV+/HIV+ patients Greater increase of LEE in previously naïve HCV+/HIV+ patients who started DRV/r Baseline ALT are still relevant to LEE even if LEE were classified based on changes relative to baseline value than upper limit normal

11 ICONA BOARD OF DIRECTORS M. Moroni (Chair), G. Angarano, A. Antinori,, O. Armignacco, A. d Arminio Monforte, F. Castelli, R. Cauda,, G. Di Perri, M. Galli, R. Iardino, G. Ippolito, A. Lazzarin, C.F. Perno, F. von Schloesser, P. Viale SCIENTIFIC SECRETARY A. d Arminio Monforte, A. Antinori, A. Castagna, F. Ceccherini-Silberstein, A. Cozzi-Lepri, E. Girardi, S. Lo Caputo, C. Mussini, M. Puoti STEERING COMMITTEE Massimo Andreoni, Adriana Ammassari, Andrea Antinori, Antonella d Arminio Monforte, Claudia Balotta, Paolo Bonfanti, Stefano Bonora, Marco Borderi, MRosaria Capobianchi, Antonella Castagna, Francesca Ceccherini-Silberstein, Antonella Cingolani, Paola Cinque, Alessandro Cozzi-Lepri, Antonella d Arminio Monforte, Andrea De Luca, Antonio Di Biagio, Enrico Girardi, Nicola Gianotti, Andrea Gori, Giovanni Guaraldi, Giuseppe Lapadula, Miriam Lichtner, Sergio Lo Caputo, Giordano Madeddu, Franco Maggiolo, Giulia Marchetti, Simone Marcotullio, Laura Monno, Cristina Mussini, Massimo Puoti, Eugenia Quiros Roldan, Stefano Rusconi STATISTICAL AND MONITORING TEAM A.Cozzi-Lepri, P. Cicconi, I. Fanti, T. Formenti, L. Galli, P. Lorenzini PARTICIPATING PHYSICIANS AND CENTERS Italy A. Giacometti, A. Costantini, O. Cirioni (Ancona); G. Angarano, L. Monno, C. Carrisa (Bari); F. Maggiolo, C. Suardi (Bergamo); P. Viale, E. Vanino, G. Verucchi (Bologna); F. Castelli, E. Quiros Roldan, C. Minardi (Brescia); T. Quirino, C. Abeli (Busto Arsizio); P.E. Manconi, P. Piano (Cagliari); J. Vecchiet, K. Falasca (Chieti); L. Sighinolfi, D. Segala (Ferrara); F. Mazzotta, S. Lo Caputo (Firenze); G. Cassola, G. Viscoli, A. Alessandrini, R. Piscopo, G. Mazzarello (Genova); C. Mastroianni, V. Belvisi (Latina); P. Bonfanti, I. Caramma (Lecco); A. P. Castelli (Macerata); M. Galli, A. Lazzarin, G. Rizzardini, M. Puoti, A. d Arminio Monforte, A.L. Ridolfo, R. Piolini, A. Castagna, S. Salpietro, L. Carenzi, M.C. Moioli, P. Cicconi, G. Marchetti (Milano); C. Mussini, C. Puzzolante (Modena); A. Gori, G. Lapadula (Monza); N. Abrescia, A. Chirianni, M.G. Guida, M. Gargiulo (Napoli); F. Baldelli, D. Francisci (Perugia); G. Parruti, T. Ursini (Pescara); G. Magnani, M.A. Ursitti (Reggio Emilia); R. Cauda, M. Andreoni, A. Antinori, V. Vullo, A. Cingolani, A. d Avino, A. Ammassari, L. Gallo, E. Nicastri, R. Acinapura, M. Capozzi, R. Libertone, G. Tebano (Roma); A. Cattelan (Rovigo); M.S. Mura, G. Madeddu (Sassari); P. Caramello, G. Di Perri, G.C. Orofino, S. Bonora, M. Sciandra (Torino); G. Pellizzer, V. Manfrin (Vicenza).