HIV/HCV coinfection in Spain Trouble will soon be over

Chiara Fanciulli1, Juan Berenguer1, Carmen Busca2, Santos Del Campo3, Lourdes Domínguez4,

Jordi Navarro5, María J. Téllez6, Pere Domingo7, José A. Iribarren8, Antonio Rivero Román9, Manuel Márquez10,

Arturo Artero11, Luis Morano12, Ignacio Santos13, Javier Moreno14, Carlos Armiñanzas15, María J. Galindo16,

Inmaculada Jarrín17, Marta De Miguel18, Juan González Garcia2, and GeSIDA 8514 Study Group

1Hospital General Universitario Gregorio Marañón, Madrid, 2Hospital Universitario La Paz, Madrid, 3Hospital Ramón y Cajal, Madrid, 4Hospital Universitario 12 de

Octubre, Madrid, 5Hospital Universitari Vall d´Hebrón, Barcelona, 6Hospital Clínico San Carlos, Madrid, 7Hospital de la Santa Creu i Sant Pau, Barcelona, 8Hospital

Donostia, San Sebastián, 9Hospital Universitario Reina Sofía, Córdoba, 10Hospital Clínico Universitario Virgen de la Victoria, Málaga, 11Hospital Universitario Doctor

Peset, Valencia, 12Hospital Universitario Álvaro Cunqueiro, Vigo, 13Hospital Universitario de la Princesa, Madrid, 14Hospital Universitario Miguel Servet, Zaragoza, 15Hospital Universitario Marqués de Valdecilla, Santander, 16Hospital Clínico de Valencia, Valencia, 17Instituto de Salud Carlos III, Madrid, 18Fundación SEIMC/GeSIDA,

Madrid

OR-13

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

MethodsDesign • Nationwide cross-sectional study

Study period • October-November 2018

Reference population

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

Sample size estimation

• Confidence level 95% / Design effect 1.0 / Accuracy of 1.25%

Patient selection

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

Data capture • Online CRF

Ethical issues • The Institutional Ethics Committee of Hospital General Universitario Gregorio Marañón approved the study

*Active follow-up = at least 1 visit in the previous 12 months

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

Summary of findings

Centers • 43 centers

Referencepopulation

• 40,650 PLHIV

Sample size • 1,733 PLHIV

HCVserology

• Known in 1,721 (99.3%) patients• 578 of whom were HCV Ab+

• 409 were HCV-RNA(–) following SVR• 64 patients were HCV-RNA(+)

• 104 cleared HCV-RNA spontaneously• 1 unknown HCV-RNA

Prevalence HCV Ab+ = 33.6 % (IC 95% 31.3 – 35.9)HCV RNA+ = 3.7 % (IC 95% 2.9 – 4.7)

Prevalence of HCV infection

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Anti-HCV exposure in patients with active HCV infection

21 patients with active HCV infection were receiving all oral DAAs

• 9 SOF/VEL+-RBV• 5 GLE/PIB• 5 SOF/LDV+-RBV• 1 EBR/GZR+-RBV• 1 OBV/PTV/R+DSV+RBV

Assuming SVR rate of 95%, the prevalence of active HCV infection could be 2.5%

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Time since HCV infection diagnosis

In patients with active HCV infection (HCV RNA+)

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Patients with active HCV infection not receiving anti-HCV therapy

Reasons for not receiving therapy

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

Patients with TE = 53 (82.8%) Patients with FIB-4 = 64 (100%)

HCV genotypes and fibrosis in patient with active HCV infection (N=64)

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

HIV/HCV coinfection in Spain: 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 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. Fanciulli C, et al. X Congreso Nacional de GeSIDA, 2018 (Abstract # OR-14)6. Fanciulli C, et al. XI Congreso Nacional de GeSIDA, 2019 (Abstract # OR-13)

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

Mechanisms of HIV transmission

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

Prevalence of HCV infection

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

Treatment Uptake

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Percentage of patients with current or past chronic HCV infection exposed to anti-HCV therapy

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

Prevalence of HCV infection according to transmission category

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

HIV transmission categories

among patients with active HCV

infection

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

Patients with reinfection

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Active HCV infection with a prior SVR

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

Features of liver cirrhosis in patients with active HCV and those who cleared HCV following anti-HCV therapy (SVR)

Active HCV

N = 64

Clearance of HCV following anti-HCV therapy (SVR)

N = 406

P

Liver cirrhosis, n (%) 7 (10.9) 108 (26.4) 0.007

Decompensated cirrhosis, n (%) 1 (14.3) 15 (13.9) 0.977

Hepatocellular carcinoma, n (%) 1 (14.3) 3 (2.8) 0.107

Serum albumin, median (IQR) 4.7 ( 3.8 – 4.9) 4.5 (4.1 – 4.7) 0.369

FIB-4 value - Median (IQR)* 2.8 (2.5 – 4.1) 2.0 (1.3 – 2.9) 0.153

Last TE value – kPa, median (IQR)≠ 23.9 (16.3 – 29.1) 14.5 (10.0 – 25.0) 0.240

*FIB-4 was available in 7 (100%) of patients with active HCV and in 106 (98.1%) of patients who cleared HCV after anti-HCV therapy≠ TE was available in 6 (85.7%) of patients with active HCV and in 104 (96.3%) of patients who cleared HCV after anti-HCV therapy

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

Cirrhosis among PLHIV

• Prevalence of cirrhosis• 115/1,733 (6.6%) overall

• 7/64 (10.9%) with active HCV infection

• 108/406 (26.4%) who cleared HCV after anti-HCV therapy (SVR)

• Assuming 130K-140K PLHIV in Spain• There are between 8,580 and 9,240 PLHIV

with HCV-related cirrhosis

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Definition of cirrhosis: Liver biopsy, TE >12.5 kPa), or clinical/biological findings

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

Conclusions

1. The prevalence of HCV-RNA+ among HIV-infected individuals in Spain at the end of 2018 was 3.7%, that is, 83.3% lower than in 2015 in which the prevalence was 22.1%.

2. Increased exposure to DAA-based therapy was the main reason for this sharp decrease.

3. Our findings suggest that the elimination of HCV infection among HIV-infected patients in Spain is an achievable goal in the near future.

4. The burden of HCV-related cirrhosis, however, will continue to be significant among HIV-infected individuals.

HIV/HCV-Coinfection in Spain - 2018 GeSIDA

Fanciulli C, et al. XI Congreso Nacional GeSIDA – 2019. Abstract OR-13

GeSIDA 2019

GeSIDA 8514 Study GroupHospital Gregorio Marañón, Madrid: C Fanciulli, L Pérez-Latorre, P Miralles, JC López, F Parras, B Padilla, T Aldámiz, C Díez, F Tejerina, and J Berenguer. Hospital La Paz, Madrid: C Busca, A Delgado, V Hontañón, R de Miguel, R Micán, F Arnalich, JR Arribas, JI Bernardino, ML Martín-Carbonero, R Montejano, ML Montes, V Moreno, I Pérez-Valero, 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, R Rubio, and F Pulido. Hospital Vall d´Hebrón, Barcelona: J Navarro, A Torrella, N Ramos, and B Planas. Hospital Clínico San Carlos, Madrid: V Estrada, J Vergas, and MJ Téllez. Hospital Santa Creu i Sant Pau, Barcelona: J Muñoz, L Millán, M Gutiérrez, G Mateo, JM Guardiola, and P Domingo. 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: A Camacho, IM Machuca, A Rivero-Juárez, I Reyes, I Ruiz, 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, S Castro, and M Crespo. Hospital de la Princesa, Madrid: L García, S Otero, A Bautista, 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: R Ferrando-Vilalta, A Ferrer, and MJ Galindo. Hospital La Fe, Valencia: M Montero, M Tasias, S Cuellar, E Calabuig, M Blanes, J Fernández, I Castro, J López-Aldeguer, and M Salavert. Hospital Son Llátzer, Palma de Mallorca: C Cifuentes. Hospitales Universitarios Arnau de Vilanova y Santa María, Lleida. T Puig. 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, G López, and B de la Fuente. Centro SanitarioSandoval, Madrid: C Rodríguez, T Puerta, M Raposo, M Vera, and J Del Romero. Hospital General de Alicante, Alicante: S Reus, M Carreres, 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: V Sánchez, and 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 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, Albacete: E Gómez Alfaro. Hospital San Eloy-OSI, Baracaldo: R Silvariño. Hospital Infanta Elena, Valdemoro: V Víctor. 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. Fundación SEIMC-GESIDA, Madrid: M De Miguel, and H Esteban.

Principal Investigators: J Berenguer and J GonzálezStudy Coordinator: M De Miguel - Statistician: I Jarrin

GeSIDA 2019