Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain 1997-2008 J. Berenguer1, B. Alejos2, V. Hernando2,

Presentación del tema: "Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain 1997-2008 J. Berenguer1, B. Alejos2, V. Hernando2,"— Transcripción de la presentación:

1 Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain J. Berenguer1, B. Alejos2, V. Hernando2, P. Viciana3, J.A. Oteo4, J.L. Gómez Sirvent5, D. Dalmau6, J.Portilla7, S. Moreno8, J. Del Amo2, and CoRIS 1Hosp General Universitario Gregorio Marañón, Madrid, 2National Epidemiology Centre, ISCIII, Madrid, 3Hosp Virgen del Rocío, Sevilla, 4Hosp San Pedro-CIBIR, Logroño, 5Hosp Universitario de Canarias, Las Palmas, 6Hosp Mutua Tarrasa, Tarrasa, 7Hosp General de Alicante, Alicante, 8Hosp Ramón y Cajal, Madrid, Spain

2 Introduction

3 Background End-stage liver disease has been a frequent cause of death in HIV+ patients in areas with a high prevalence of coinfection with HCV. In the last decade, several factors could have influenced liver-related mortality in the HIV+ population in Spain Sharp decline of HCV prevalence in new HIV+ patients Availability of IFN + RBV for treatment of HCV More efficacious and safe cART regimens 3

4 Parallel decline of IDU and HCV coinfection prevalence
Cachafeiro S, et al. Clinical Infectious Diseases 2009; 48:

5 Aims To assess trends in overall mortality and cause-specific mortality stratified by HCV serostatus in a cohort of naïve HIV-infected patients in Spain.

6 Methods

7 Patients and calendar periods
1st Period: 1 Jan 1997 – 31 Dec 2003 CoRIS-MD (N= 2,562) Retrospectively built cohort 10 centers (7 regions) 2nd Period: 1 Jan 2004 – 31 Dec 2008 CoRIS (N= 3,503) Prospective cohort 29 centers (13 regions) Inclusion criteria HIV + (EIA & WB) Age >18 years ART-naïve At least 6 mo of FU

8 Mortality Deaths were ascertained through cohort reporting and a cross-match with the Spanish National Death Index (NDI) We used NDI coding (IDC-9 and IDC-10) to categorize death as AIDS-related Liver-related (codes B15-B19, C22-C229, K70-K77, K922, K65, R18) Non–liver-related non–AIDS-related

9 Statistics Descriptive statistics
Mortality rates per 1000 persons-years We used Poisson regression to model mortality rates and risk factors Perfil sociodemográfico, epidemiológico y clínico de pacientes adultos con infección por VIH según su edad 9

10 Results

11 Baseline characteristics of patients stratified by calendar period
HCV Negative 974 (38) (80,3) <0.001 Positive 1497 (58.4) 689 (19.7) Unkown 91 (3.6) 0 () Male sex-n (%) 1856 (72.4) 2737 (78.1) Age at entry-yr, median (IQR) 34.4 ( ) 35.9 ( ) HIV-transmission category-n (%) MSM 369 (14.4) 1583 (45.2) IDU 1376 (53.7) 530 (15.1) Hetero 603 (23.5) 1259 (35.9) Other/unknown 214 (8.4) 131 (3.7) CDC disease category C-n (%) 295 (11.5) 490 (14.0) CD4 cells /mm3-n (%) <200 627 (24.5) 1047 (29.9) 388 (15.1) 713 (20.4) >350 909 (35.5) 1662 (47.4) Unknown 638 (24.9) 81 (2.3) HIV RNA copies/mL-n (%) < 100,000 copies/mL 1110 (43.3) 2242 (64) ≥ 100,000 copies 453 (17.7) 1178 (33.6) 999 (39) 83 (2.4) The most striking differences between patients in both periods relate to HCV infection, sex and HIV-transmission categories. In the second period patients were more frequently free from HCV infection and had adcquired HIV infection predominantly by sex and not by IDU 11

12 Deaths stratified by calendar period
Cause of death Total HIV/AIDS-related 141 99 42 Non-liver/Non-AIDS 84 58 26 Liver-related 25 19 6 250 176 74 A total of 250 deaths were identified, 176 during the first period and 74 during the second period. In both periods HIV was the leading cause of mortality followed by non-liver-related non-aids related causes and finally by liver disease 12

13 Overall and cause-specific death rates stratified by calendar period
This graph shows death rates per 1000 person-years and 95% confidence interval stratified by calendar period. It can be appreciate a decline in overall and cause-specific mortality in HIV-infected patients in Spain Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain; 13 13

14 Overall death rates stratified by HCV-status and period
IRR (95%CI) ref * HCV- 0.52 ( ) HCV+ 1.27 ( ) We analyze overall death rates stratified by HCV-status and calendar period. Number of events and py of FU are shown in the small pink boxes. In the large red box you can see Crude Incidence Rate Ratios of death in the second period taking the first period as reference and categorized by HCV-status. In summary, we observed a significant decrease in overall death rate was observed among HCV negative patients whereas a non-significant increase was observed among HCV positive patients n 32 py 3619.6 n 32 py 6965.6 n 126 py 6752.5 n 42 py 1779.2 *crude incidence rate ratio (and 95% CI) of death in period taking death rates in as reference Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain; 14 14

15 AIDS-related death rates stratified by HCV-status and period
IRR (95%CI) ref * HCV- 0.71 ( ) HCV+ 1.01 ( ) Lets now move to cause-specific death rates stratified by HCV-status and period and lets start with AIDS-related death rates. We observed a decrease in AIDS-related death rate in the limits of statiscal signifcance for HCV negatives, whereas AIDS-related death rates remained virtually unchanged among HCV positives n 16 py 3619.6 n 22 py 6965.6 n 69 py 6752.5 n 20 py 1779.2 *crude incidence rate ratio (and 95% CI) of death in period taking death rates in as reference Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain; 15 15

16 Liver-related death rates stratified by HCV-status and period
IRR (95%CI) ref * HCV- 0.17 ( ) HCV+ 1.19 ( ) Liver related death rates decreased among HCV-negatives whereas they remained virtually unchanged among HCV positives HCV - HCV + n 3 py 3619.6 n 1 py 6965.6 n 16 py 6752.5 n 5 py 1779.2 *crude incidence rate ratio (and 95% CI) of death in period taking death rates in as reference Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain; 16 16

17 Non–liver-related non–AIDS-related death rates stratified by HCV-status and period
IRR (95%CI) ref * HCV- 0.36 ( ) HCV+ 1.57 ( ) Non-liver related Non-AIDS-related death rates decreased significantly among HCV-negatives. However, among HCV-positives death rates increased non-significantly n 13 py 3619.6 n 9 py 6965.6 n 41 py 6752.5 n 17 py 1779.2 *crude incidence rate ratio (and 95% CI) of death in period taking death rates in as reference Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain; 17 17

18 Non–liver-related non–AIDS-related causes of death stratified by HCV-status
Cause of death HCV + HCV - Cardiovascular 14 5 Accidental poisoning 9 Trauma 7 1 Suicide 6 Non-AIDS malignancy 4 Non-AIDS infections Other causes TOTAL 58 22 This slide shows the different non-liver-related non-AIDS-related causes of death stratified by HCV status and period. The leading causes in this category were cardiovascular conditions and non-AIDS defining malignancies followed by accidental poisoning, trauma, non-aids infection, suicide and other conditions Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain; 18 18

19 Conclusions Taking the first years of the cART era as reference, we observed a decline in overall and cause-specific mortality in naïve HIV-infected patients in Spain These trends were largely at the expense of patients without HCV infection as declines were not observed among HCV-infected patients A suggestion of increases in non-AIDS-related non-liver-related deaths among HCV-infected patients has been observed in recent years

20 Acknowledgements This study would not have been possible without the collaboration of all the patients, medical and nursing staff, and data managers who have taken part in the project. The RIS Cohort (CoRIS) is funded by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en Sida (RIS C03/173).

21 CoRIS MEMBERS Hospital General Universitario de Alicante (Alicante): Joaquín Portilla Sogorb, Esperanza Merino de Lucas, Sergio Reus Bañuls, Vicente Boix Martínez, Livia Giner Oncina, Carmen Gadea Pastor, Irene Portilla Tamarit, Patricia Arcaina Toledo. Hospital Universitario de Canarias (Santa Cruz de Tenerife): Juan Luis Gómez Sirvent, Patricia Rodríguez Fortúnez, María Remedios Alemán Valls, María del Mar Alonso Socas, Ana María López Lirola, María Inmaculada Hernández Hernández, Felicitas Díaz-Flores. Hospital Carlos III (Madrid): Vicente Soriano, Pablo Labarga, Pablo Barreiro, Carol Castañares, Pablo Rivas, Andrés Ruiz, Francisco Blanco, Pilar García, Mercedes de Diego. Hospital Universitario Central de Asturias (Oviedo): Victor Asensi, Eulalia Valle, José Antonio Cartón Hospital Clinic (Barcelona): José M. Miró, María López-Dieguez, Christian Manzardo, Laura Zamora, Iñaki Pérez, Mª Teresa García, Carmen Ligero, José Luis Blanco, Felipe García-Alcaide, Esteban Martínez, Josep Mallolas, José M. Gatell Hospital Doce de Octubre (Madrid): Rafael Rubio, Federico Pulido, Silvana Fiorante, Jara Llenas, Violeta Rodríguez, Mariano Matarranz. Hospital Donostia (San Sebastián): José Antonio Iribarren, Julio Arrizabalaga, María José Aramburu, Xabier Camino, Francisco Rodríguez-Arrondo, Miguel Ángel von Wichmann, Lidia Pascual Tomé, Miguel Ángel Goenaga, Mª Jesús Bustinduy, Harkaitz Azkune Galparsoro Hospital General Universitario de Elche (Elche): Félix Gutiérrez, Mar Masiá, José Manuel Ramos, Sergio Padilla, Andrés Navarro, Fernando Montolio, Yolanda Peral, Catalina Robledano García Hospital Germans Trías i Pujol (Badalona): Bonaventura Clotet, Cristina Tural, Lidia Ruiz, Cristina Miranda, Roberto Muga, Jordi Tor, Arantza Sanvisens Hospital Gregorio Marañón (Madrid): Juan Berenguer, Juan Carlos López Bernaldo de Quirós, Pilar Miralles, Jaime Cosín Ochaíta, Matilde Sánchez Conde, Isabel Gutiérrez Cuellar, Margarita Ramírez Schacke, Belén Padilla Ortega, Paloma Gijón Vidaurreta. Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili (Tarragona): Francesc Vidal, Joaquín Peraire, Consuelo Viladés, Sergio Veloso, Montserrat Vargas, Miguel López-Dupla, Montserrat Olona, Joan-Josep Sirvent, Alba Aguilar, Antoni Soriano. Hospital Universitario La Fe (Valencia): José López Aldeguer, Marino Blanes Juliá, José Lacruz Rodrigo, Miguel Salavert, Marta Montero, Eva Calabuig, Sandra Cuéllar. Hospital Universitário La Paz (Madrid): Juan González García, Ignacio Bernardino de la Serna, José María Peña Sánchez de Rivera, Marta Mora Rillo, José Ramón Arribas López, María Luisa Montes Ramírez, José Francisco Pascual Pareja, Blanca Arribas, Juan Miguel Castro, Fco Javier Zamora Vargas, Ignacio Pérez Valero. Hospital de la Princesa (Madrid): Ignacio de los Santos, Jesús Sanz Sanz, Johana Rodríguez, Ana Salas Aparicio, Cristina Sarriá Cepeda. Hospital San Pedro-CIBIR (Logroño): José Antonio Oteo, José Ramón Blanco, Valvanera Ibarra, Luis Metola, Mercedes Sanz, Laura Pérez-Martínez Hospital San Pedro II (Logroño): Javier Pinilla Moraza Hospital Universitario Mutua de Terrassa (Terrassa): David Dalmau, Angels Jaén Manzanera, Mireia Cairó Llobell, Daniel Irigoyen Puig, Laura Ibáñez, Queralt Jordano Montañez, Mariona Xercavins Valls, Javier Martinez-Lacasa, Pablo Velli, Roser Font. Hospital de Navarra (Pamplona): Julio Sola Boneta, Javier Uriz, Jesús Castiello, Jesús Reparaz, María Jesús Arraiza, Carmen Irigoyen, David Mozas, Hospital Parc Taulí (Sabadell): Ferrán Segura, María José Amengual, Eva Penelo, Gemma Navarro, Montserrat Sala, Manuel Cervantes, Valentín Pineda. Hospital Ramón y Cajal (Madrid): Santiago Moreno, José Luis Casado, Fernando Dronda, Ana Moreno, María Jesús Pérez Elías, Dolores López, Carolina Gutiérrez, Beatriz Hernández, María Pumares, Paloma Martí. Hospital Reina Sofía (Murcia): Alfredo Cano Sánchez, Enrique Bernal Morell, Ángeles Muñoz Pérez Hospital San Cecilio (Granada): Federico García García, José Hernández Quero, Alejandro Peña Monje, Leopoldo Muñoz Medina, Jorge Parra Ruiz. Centro Sanitario Sandoval (Madrid): Jorge Del Romero Guerrero, Carmen Rodríguez Martín, Teresa Puerta López, Juan Carlos Carrió Montiel, Cristina González. Hospital Universitario Santiago de Compostela (Santiago de Compostela): Antonio Antela, Arturo Prieto, Elena Losada Hospital Son Dureta (Palma de Mallorca): Melchor Riera, Javier Murillas, Maria Peñaranda, Maria Leyes, Mª Angels Ribas, Antoni Campins, Concepcion Villalonga. Hospital Universitario de Valme (Sevilla): Juan Antonio Pineda, Eva Recio Sánchez, Fernando Lozano de León, Juan Macías, José del Valle, Jesús Gómez-Mateos, Rosario Mata. Hospital Virgen de la Victoria (Málaga): Jesús Santos González, Manuel Márquez Solero, Isabel Viciana Ramos, Rosario Palacios Muñoz Hospital Universitario Virgen del Rocío (Sevilla): Pompeyo Viciana, Manuel Leal, Luis Fernando López-Cortés, Mónica Trastoy Steering Comitee: Juan Berenguer, Julia del Amo, Federico García, Félix Gutiérrez, Pablo Labarga, Santiago Moreno y María Ángeles Muñoz Data Managementand statistical analyses: Ana María Caro-Murillo, Paz Sobrino Vegas, Santiago Pérez-Cachafeiro, Victoria Hernando Sebastián, Belén Alejos Ferreras, Débora Álvarez, Susana Monge, Inma Jarrín, Mónica Trastoy BioBank: M Ángeles Muñoz-Fernández, Isabel García-Merino, Coral Gómez Rico, Jorge Gallego de la Fuente y Almudena García Torre 21