HIV/HBV coinfection in Spain: Prevalence and clinical characteristics

Leire Pérez-Latorre 1, Juan Berenguer 1, Rafael Micán 2, Marta Montero 3, Carmen Cifuentes 4, Teresa Puig 5, José Sanz 6, Oscar L Ferrero 7, Belén De La Fuente 8, Carmen Rodríguez 9, Sergio Reus 10, José Hernández-Quero 11, Gabriel Gaspar

12, Laura Pérez-Martínez 13, Coral García 14, Luis Force 15, Sergio Veloso 16, Marta De Miguel 17, Inmaculada Jarrín 18, Juan González 2, and GeSIDA 8514 Study Group

1Hospital General Universitario Gregorio Marañón, Madrid, 2Hospital Universitario La Paz, Madrid, 3Hospital Universitario La Fe, Valencia, 4Hospital Son Llàtzer, Son Ferriol, 5Hospital Universitari Arnau de Vilanova, Lleida, 6Hospital Príncipe de Asturias, Alcalá de Henares, 7Hospital de Basurto, Bilbao, 8Hospital de Cabueñes, Gijón, 9Centro Sanitario Sandoval, Madrid, 10Hospital General Universitario de Alicante, Alicante,

11Hospital Clínico Universitario San Cecilio, Granada, 12Hospital Universitario de Getafe, Getafe, 13Hospital General de La Rioja, Logroño, 14Hospital Universitario Virgen de las Nieves, Granada, 15Hospital de Mataró, Mataró, 16Hospital Universitari Joan XXIII, Tarragona,

17Fundación SEIMC/GESIDA, Madrid, 18Instituto de Salud Carlos III, Madrid

OR-01GeSIDA 2019

Background

• In HIV infected patients, coinfection with HBV has been associated with increased levels of HBV DNA, accelerated progression of liver disease and increased all-cause and liver-related mortality.

• Rates of chronic HBV in HIV infected individuals vary significantly between regions and risk-based groups, reflecting different patterns of transmission and immunization coverage.

• We assessed the prevalence of HIV/HBV coinfection in Spain in 2018 and compared the results with similar studies performed in 2002, 2009, 2015, 2016, and 2017.

1 Thornton, A.C., et al., AIDS, 2017. 31: 2525-25322 Singh, K.P. Et al., AIDS, 2017: 31: 2035-2052

HIV/HBV coinfection in Spain - 2018

Pérez-Latorre L, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-01

GeSIDA 2019

Methods

Design • Nationwide prevalence study of HIV/HCV and HIV/HBV coinfections

Study period • October-November 2018

Reference population

• All HIV+ patients in active follow-up in the participating centers*

Sample size estimation

• The sample size was estimated to assess the prevalence of HCV with a confidence level 95% / Design effect 1.0 / Accuracy of 1.25%. The accuracy for estimation of the prevalence of HBsAg was 0.8%.

Patient selection

• Nº of patients from each hospital determined by proportional allocation• Patients were selected using simple random sampling

Data capture • Online case report form

Ethical issues • The Ethics Committee of HGUGM# approved the study

*Active follow-up = at least 1 visit in the previous 12 months# Hospital General Universitario Gregorio Marañón

HIV/HBV coinfection in Spain - 2018

Pérez-Latorre L, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-01

GeSIDA 2019

GeSIDA prevalence studies

Variable 20021 20092 20153 20164 20175 20186

Participating centers 39 43 41 43 43 43

Reference population 31,800 29,559 35,791 38,904 40,322 40,650

Sample size 1,260 1,458 1,867 1,588 1,690 1,733

Tested for HBsAg 92.7% 97.7% 97.1% 97.5% 96.2% 96.5%

Tested for HCV antibodies 99.5% 99.8% 98.7% 99.8% 99.1% 99.3%

1. González J, et al Enferm Infecc Microbiol Clin 2005; 23:340–8.2. González J, et al. IV Congreso Nacional de GeSIDA; 2012.3. Berenguer J, et al. Open Forum Infect Dis 2016;3:ofw0594. Berenguer J, et al. Open Forum Infect Dis 2018;5:ofw2585. Pérez-Latorre L, et al. X Congreso Nacional de GeSIDA, 2018 (Abstract # P-029)6. Pérez-Latorre L, et al. 17th European AIDS Conference, 2019 (Abstract # PS12/4)

HIV/HBV coinfection in Spain - 2018

Pérez-Latorre L, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-01

GeSIDA 2019

Prevalence of HBsAg+ among HIV-infected subjects

HIV/HBV coinfection in Spain - 2018

Pérez-Latorre L, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-01

GeSIDA 2019

Demographics and HIV-related variablesHBsAg Total

Characteristic Unknown Positive Negative P✱ N = 1,733

N = 60 (3.5) N = 54 (3.1) N = 1,619 (93.4)

Male sex, n (%) 44 (73.3) 44 (81.5) 1,202 (74.2) .230 1,290 (74.4)

Age years, mean (SD) 51 (10) 50 (11) 49 (11) .367 49 (11)

HIV transmission category, n (%) .174

Injection drug use 19 (31.7) 21 (38.9) 455 (28.1) 495 (28.6)

Heterosexual 15 (25.0) 8 (14.8) 440 (27.2) 463 (26.7)

Male sex with male 7 (11.7) 21 (38.9) 603 (37.2) 631 (36.4)

Mother to child transmission 0 1 (1.8) 12 (0.7) 13 (0.7)

Other 19 (31.7) 2 (3.7) 99 (6.1) 120 (6.9)

CDC clinical category C, n (%) 13 (21.7) 15 (27.8) 419 (25.9) .939 447 (25.8)

Patients on cART, n (%) 60 (100) 52 (96.3) 1587 (98.0) .601 1699 (98.0)

HIV RNA < 50 copies/ml, n (%) 52 (86.7) 50 (96.1) 1478 (93.1) .819 1580 (93.0)

CD4+ – T cells/uL, median (IQR) 598 (410-951) 637 (343-836) 698 (480-919) .031 695 (471-915)✱P-values for the comparisons between HBsAg-positive patients and HBsAg-negative patients

HIV/HBV coinfection in Spain - 2018

Pérez-Latorre L, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-01

GeSIDA 2019

Liver-disease related variables

HBsAg Total

Characteristic Unknown Positive Negative P✱ N = 1,733

N = 60 (3.5) N = 54 (3.1) N = 1,619 (93.4)

HCV antibodies, n (%) 26 (43.3) 22 (40.7) 530 (32.7) .445 578 (33.3)

HCV RNA, n (%)

Positive

Negative post Rx

Negative spontaneous clearance

Unknown

4 (15.4)20 (76.9)

2 (7.7)0

3 (13.6)7 (31.8)

12 (54.5)0

59 (11.1)380 (71.7)90 (17.0)

1 (0.2)

<.001 66 (11.4)407 (70.4)104 (18.0)

1 (0.2)

eGFR CKDEPI, median (IQR) 97.6

(77.3-104.3)

93.6

(79.0-103.3)

92.2

(78.4-103.2)

.989 92.4

(78.5-103.3)

✱P-values for the comparisons between HBsAg-positive patients and HBsAg-negative patients

HIV/HBV coinfection in Spain - 2018

Pérez-Latorre L, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-01

GeSIDA 2019

Liver stiffness (kPa) in 30 (55.5%) out of 54 patients HBsAg+

HIV/HBV coinfection in Spain - 2018

Pérez-Latorre L, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-01EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.https://easl.eu/publication/management-of-hepatitis-b-virus-infection/

F4

F3

F0-F2

GeSIDA 2019

Anti-HBV therapy in 54 patients HBsAg positive

All patients received at least one drug with anti-HBV activity

HIV/HBV coinfection in Spain - 2018

Pérez-Latorre L, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-01

GeSIDA 2019

HBV-DNA in 54 patients HBsAg positivePercentage of those tested in the prior 12 mo.

HIV/HBV coinfection in Spain - 2018

Pérez-Latorre L, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-01

GeSIDA 2019

HDV-Ab in 54 patients HBsAg positivePercentage of those ever tested

HIV/HBV coinfection in Spain - 2018

Pérez-Latorre L, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-01

GeSIDA 2019

Conclusions

1. The prevalence of HIV/HBV coinfection in Spain at the end of 2018

was 3.2%.

2. This prevalence does not differ significantly from those reported in

studies performed over the last 15 years.

3. All HIV/HBV coinfected patients were on anti-HBV drugs, and most

had full suppression of HBV-DNA.

4. Liver cirrhosis and HDV infection were identified as common

problems among HIV/HBV-coinfected patients.

HIV/HBV coinfection in Spain - 2018

Pérez-Latorre L, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-01

GeSIDA 2019

GeSIDA 8514 Study Group

Hospital Gregorio Marañón, Madrid: C Fanciulli, L Pérez-Latorre, P Miralles, JC López, F Parras, B Padilla, T Aldámiz, A Carrero, C Díez, F Tejerina, and J Berenguer. Hospital La Paz, Madrid: V Hontañón, C Busca, A Delgado, R Micán, F Arnalich, JR Arribas, JI Bernardino, ML Martín-Carbonero, R Montejano, ML Montes, V Moreno, I Pérez-Valero, C Navarro, E Valencia, and J González-García. Hospital Ramón y Cajal, Madrid: MJ Vivancos, S Moreno, A Moreno, JL Casado, MJ Pérez-Elías, and C Quereda. Hospital 12 de Octubre, Madrid: L Domínguez, A Hernando, O Bisbal, M De Lagarde, M Matarranz, Rafael Rubio, and F Pulido. Hospital Vall d´Hebrón, Barcelona: J Navarro, A Torrella, and N Ramos. Hospital Clínico San Carlos, Madrid: M Rodrigo, V Estrada, J Vergas, and MJ Téllez. Hospital Santa Creu i Sant Pau, Barcelona: J Muñoz, M Gutiérrez, G Mateo, and JM Guardiola. Hospital Donostia, San Sebastián: M Ibarguren, MP Carmona, F Rodríguez-Arrondo, MA Goenaga, H Azkune, MA Von Wichmann, and JA Iribarren. Hospital Reina Sofía, Córdoba: T Brieva, A Camacho, IM Machuca, A Rivero-Juárez, and A Rivero-Román. Hospital Virgen de la Victoria, Málaga: J Ruiz, E Nuño, R Palacios, J Santos, and M Márquez. Hospital Doctor Peset, Valencia: J Carmena, and A Artero. Hospital Universitario Alvaro Cunqueiro, Vigo: L Morano, and M Crespo. Hospital de la Princesa, Madrid: L García, S Otero, J Sanz, and I Santos. Hospital Miguel Servet, Zaragoza: J Moreno, and P Arazo. Hospital Marques de Valdecilla, Santander: C Armiñanzas, S Echevarría, M Gutiérrez-Cuadra, and MC Fariñas. Hospital Clinico de Valencia, Valencia: A Ferrer, and MJ Galindo. Hospital La Fe, Valencia: M, Montero, M Tasias, S Cuellar, E Calabuig, M Blanes, J Fernández, J López-Aldeguer, and M Salavert. Hospital Son Llátzer, Palma de Mallorca: C Cifuentes. Hospitales Universitarios Arnau de Vilanova y Santa María, Lleida. P Domingo. Hospital Príncipe de Asturias, Alcalá de Henares: J de Miguel, A Arranz, E Casas, and J Sanz. Hospital Universitario Basurto, Bilbao: OL Ferrero, S Ibarra, I López, M de la Peña, Z Zubero, J Baraia, and J Muñoz. Hospital de Cabueñes, Gijón: M Campoamor, MJ Tuya, and B de la Fuente. Centro Sanitario Sandoval, Madrid: C Rodríguez, T Puerta, M Raposo, M Vera, and J Del Romero. Hospital General de Alicante, Alicante: S Reus, L Giner, E Merino, V Boix, D Torrús, I Portilla, M Pampliega, M Díez, I Egea, and J Portilla. Complejo Hospitalario Universitario de Granada, Granada: D Vinuesa, L Muñoz, and J Hernández-Quero. Hospital Universitario de Getafe, Getafe: G Gaspar. Hospital San Pedro -CIBIR: Logroño: L García, L Pérez, and JA Oteo. Hospital Virgen de las Nieves, Granada: C García. Hospital de Mataró, Mataró: L Force, and P Barrufet. Hospital Universitari de Tarragona Joan XXIII, Tarragona: S Veloso, J Peraire, C Viladés, M Vargas, A Castellano, and F Vidal. Hospital Fundación de Alcorcón, Alcorcón: M Velasco, L Moreno, R Hervás, and JE Losa. Hospital Universitari de Vic, Vic: J Vilaró. Hospital Reina Sofía, Murcia: A Cano, A Alcaráz, A Muñoz, and E Bernal. Hospital Universitario de Torrejón: Torrejón de Ardoz: A Gimeno, C Montero, and S Arponen. Hospital Virgen de la Cinta, Tortosa: AJ Orti, E Chamarro, and C Escrig. Hospital Virgen de la Concha, Zamora: A Chocarro. Hospital de Sierrallana, Torrelavega: R Teira. Hospital Rafael Méndez, Lorca: G Alonso, C Toledo, AI Peláez, G Lara, I Fernández, and MC Esteban. Hospital General Universitario de Albacete: E Gómez-Alfaro. Hospital San Eloy-OSI, Baracaldo: R Silvariño. Hospital Infanta Elena, Valdemoro: A Vegas. Hospital Virgen de la Luz, Cuenca: P Geijo. Hospital d’Olot i Comarcal de la Garrotxa, Olot: J Bisbe. Instituto de Salud Carlos III, Madrid: I Jarrín.

Principal Investigators: J Berenguer and J GonzálezStudy Coordinator: H Esteban - Statistician: I JarrinGeSIDA 2019