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Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain 1997-2008. J. Berenguer 1 , B. Alejos 2 , V. Hernando 2 , P. Viciana 3 , J.A. Oteo 4 , J.L. Gómez Sirvent 5 , D. Dalmau 6 , J.Portilla 7 , S. Moreno 8 , J. Del Amo 2 , and CoRIS - PowerPoint PPT PresentationTRANSCRIPT
Temporal Trends in Liver-Related Mortality in a Prospective Cohort of
HIV-Infected Patients in Spain1997-2008
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
Introduction
Evolución de la mortalidad por causa hepática
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
Background
Evolución de la mortalidad por causa hepática Cachafeiro S, et al. Clinical Infectious Diseases 2009; 48: 1467-70
Parallel decline of IDU and HCV coinfection prevalence
Evolución de la mortalidad por causa hepática
To assess trends in overall mortality and cause-specific mortality stratified by HCV serostatus in a cohort of naïve HIV-infected patients in Spain.
Aims
Methods
Evolución de la mortalidad por causa hepática
Inclusion criteria• HIV + (EIA & WB) • Age >18 years• ART-naïve• At least 6 mo of FU
Patients and calendar periods
1st Period: 1 Jan 1997 – 31 Dec 2003CoRIS-MD (N= 2,562)• Retrospectively built cohort• 10 centers (7 regions)
2nd Period: 1 Jan 2004 – 31 Dec 2008CoRIS (N= 3,503)• Prospective cohort• 29 centers (13 regions)
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
Statistics
Perfil sociodemográfico, epidemiológico y clínico de pacientes adultos con infección por VIH según su edad 9
Descriptive statistics
Mortality rates per 1000 persons-years
We used Poisson regression to model mortality rates and risk factors
Results
Baseline characteristics of patients stratified by calendar periodCharacteristic 1997-03 (N = 2562) 2004-08 (N=3503) P
HCV Negative 974 (38) 2814 (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) <0.001Age at entry-yr, median (IQR) 34.4 (30.4-38.6) 35.9 (29.9-42.9)HIV-transmission category-n (%) <0.001 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) <0.001CD4 cells /mm3-n (%) <0.001 <200 627 (24.5) 1047 (29.9) 201-350 388 (15.1) 713 (20.4) >350 909 (35.5) 1662 (47.4) Unknown 638 (24.9) 81 (2.3)HIV RNA copies/mL-n (%) <0.001 < 100,000 copies/mL 1110 (43.3) 2242 (64) ≥ 100,000 copies 453 (17.7) 1178 (33.6) Unknown 999 (39) 83 (2.4)
Deaths stratified by calendar period
Cause of death Total 1997-03 2004-08HIV/AIDS-related 141 99 42
Non-liver/Non-AIDS 84 58 26
Liver-related 25 19 6
Total 250 176 74
Overall and cause-specific death ratesstratified by calendar period
Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain; 1997-2008 13
Overall death rates stratified by HCV-status and period
Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain; 1997-2008 14
*crude incidence rate ratio (and 95% CI) of death in period 2004-08 taking death rates in 1997-03 as reference
97-03 04-08 97-03 04-08VHC - VHC +
0
5
10
15
20
25
30
35
Deat
h ra
te x
100
0 py
(CI)
HCV - HCV +
IRR (95%CI) ref. 97-03*
HCV- 0.52 (0.32-0.85)
HCV+ 1.27 (0.90-1.79)
n 42py 1779.2
n 32py 3619.6
n 32py 6965.6
n 126py 6752.5
AIDS-related death ratesstratified by HCV-status and period
Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain; 1997-2008 15
*crude incidence rate ratio (and 95% CI) of death in period 2004-08 taking death rates in 1997-03 as reference
IRR (95%CI) ref. 97-03*
HCV- 0.71 (0.38-1.36)
HCV+ 1.01 (0.67-1.80)
n 20py 1779.2
n 16py 3619.6
n 22py 6965.6
n 69py 6752.5
Liver-related death rates stratified by HCV-status and period
Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain; 1997-2008 16
*crude incidence rate ratio (and 95% CI) of death in period 2004-08 taking death rates in 1997-03 as reference
HCV - HCV +
IRR (95%CI) ref. 97-03*
HCV- 0.17 (0.01-1.70)
HCV+ 1.19 (0.40-3.20)
n 5py 1779.2
n 3py 3619.6
n 1py 6965.6
n 16py 6752.5
Non–liver-related non–AIDS-related death rates stratified by HCV-status and period
Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain; 1997-2008 17
*crude incidence rate ratio (and 95% CI) of death in period 2004-08 taking death rates in 1997-03 as reference
IRR (95%CI) ref. 97-03*
HCV- 0.36 (0.15-0.84)
HCV+ 1.57 (0.90-2.76)
n 17py 1779.2
n 13py 3619.6
n 9py 6965.6
n 41py 6752.5
Non–liver-related non–AIDS-related causes of death stratified by HCV-status
Temporal Trends in Liver-Related Mortality in a Prospective Cohort of HIV-Infected Patients in Spain; 1997-2008 18
Cause of death HCV + HCV -Cardiovascular 14 5Accidental poisoning 9 0Trauma 7 1Suicide 6 0Non-AIDS malignancy 4 7Non-AIDS infections 4 1Other causes 14 7TOTAL 58 22
Conclusions1. 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
2. These trends were largely at the expense of patients without HCV infection as declines were not observed among HCV-infected patients
3. A suggestion of increases in non-AIDS-related non-liver-related deaths among HCV-infected patients has been observed in recent years
AcknowledgementsThis 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).
CoRIS MEMBERSHospital 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 CartónHospital 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. GatellHospital 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 GalparsoroHospital General Universitario de Elche (Elche): Félix Gutiérrez, Mar Masiá, José Manuel Ramos, Sergio Padilla, Andrés Navarro, Fernando Montolio, Yolanda Peral, Catalina Robledano GarcíaHospital Germans Trías i Pujol (Badalona): Bonaventura Clotet, Cristina Tural, Lidia Ruiz, Cristina Miranda, Roberto Muga, Jordi Tor, Arantza SanvisensHospital 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-MartínezHospital San Pedro II (Logroño): Javier Pinilla MorazaHospital 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 PérezHospital 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 LosadaHospital 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 MuñozHospital Universitario Virgen del Rocío (Sevilla): Pompeyo Viciana, Manuel Leal, Luis Fernando López-Cortés, Mónica TrastoySteering Comitee: Juan Berenguer, Julia del Amo, Federico García, Félix Gutiérrez, Pablo Labarga, Santiago Moreno y María Ángeles MuñozData 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