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Interferon Plus Ribavirin Reduces HIV Progression in HIV/HCV Coinfected Patients

This study investigates the effect of achieving a sustained virological response (SVR) after interferon plus ribavirin therapy on HIV progression and non-liver-related mortality in patients coinfected with HIV and hepatitis C virus. The results suggest that SVR reduces not only liver-related complications and mortality but also HIV progression and mortality not related to liver disease.

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Interferon Plus Ribavirin Reduces HIV Progression in HIV/HCV Coinfected Patients

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  1. Paper Sustained Virological Response to Interferon Plus Ribavirin Reduces HIV Progression and Non–Liver-Related Mortality in Patients Coinfected With Human Immunodeficiency Virus and Hepatitis C Virus Juan Berenguer*1, Manel Crespo2, María José Galindo3, María Jesús Téllez4, Carlos Barros5, José María Guardiola6, Rafael Rubio7, Elena Barquilla8, José María Bellón1, Juan González-García9, and Gesida 3603 Study Group 1Hosp. Gen. Univ. Gregorio Marañón~ 2Hosp. Univ. Vall d’Hebrón~ 3Hosp. Clínico Valencia~ 4Hosp. Clínico San Carlos~ 5Hosp. de Móstoles~ 6Hosp. Santa Creu y Sant Pau~ 7Hosp. 12 Octubre~ 8Fundación SEIMC/GESIDA~ and 9Hosp. La Paz Funding sources: Fundación para la Investigación y la Prevención del SIDA en España (FIPSE) (Refs. 36443/03 and 36702/07)

  2. Background We have previously shown that the achievement of a sustained virological response (SVR) after therapy with interferon plus ribavirin (IFN-RBV) reduces liver-related complications and mortality in HIV/HCV+ patients* 711 HIV/HCV+ patients with and without SVR * Berenguer, J. et al. Hepatology 2009;50:407-413 KM curves showing the occurrence of liver-related events

  3. Objective To determine the effect of achieving an SVR after anti-HCV therapy on HIV progression and mortality not related to liver disease.

  4. Study Design

  5. Sustained Virological Response SVR was defined as an undetectable serum HCV-RNA level 24 weeks after discontinuation of therapy Patients not fulfilling SVR criteria, including those who relapsed after achieving end of treatment response (ETR), were classified as non-SVR.

  6. Endpoints • Liver-related complications • Liver decompensation • Ascites, porto-systemic encephalopathy, upper GI bleeding • Hepatocellular carcinoma (HCC) • Histologically or clinically confirmed (high AFP values and imaging) • Liver transplantation • HIV progression • New AIDS-defining conditions (ADC); 1993 CDC Clinical Classification • Mortality* • Liver-related death • When the train of events that ended in death was caused by liver decompensation or HCC • AIDS-related death • When death was directly related to one ADC • Other causes • Non–liver-related and non–AIDS-related * Death reports, autopsy reports (if available), and protocolized formularies were requested. All the information was reviewed by a “mortality committee”, which classified deaths in accordance with the opinion of the attending clinician

  7. Patient Characteristics

  8. Treatment Regimens and SVR

  9. Treatment Regimens and SVR

  10. Treatment Regimens and SVR

  11. Frequency of Events During Follow-up Stratified According to Response to IFN-RBV

  12. Frequency of Events During Follow-up Stratified According to Response to IFN-RBV

  13. Incidence Rates of Events During Follow-up Stratified According to Response to IFN-RBV

  14. Incidence Rates of Events During Follow-up Stratified According to Response to IFN-RBV

  15. Non–Liver Non-AIDS-Related Deaths * 3 Myocardial infarction, 2 mesenteric ischemia, 1 subarachnoid hemorraghe # Myocardial infarction

  16. New AIDS-Related Conditions *Salmonella septicemia, lymphoma, toxoplasmosis

  17. Effect of non-SVR on Risk of New ADC and Non–Liver-Related Death

  18. Effect of non-SVR on Risk of New ADC and Non–Liver-Related Death *Adjusted for age, sex, prior IDU, HCV genotype, prior ADC, CD4+ nadir, and advanced fibrosis (F3-F4 on liver biopsy or APRI Index > 2)

  19. HIV-RNA < 50 copies/mL during FU

  20. CD4+ < 200 cells/mL during FU

  21. Conclusions Our results suggest that achievement of an SVR after IFN-RBV therapy in HIV/HCV+ patients reduces not only liver-related complications and mortality, but also HIV progression and mortality not related to liver disease. These findings may be associated with a poorer immune response (that does not seem to depend on control of HIV) and/or complications of HCV viremia in patients that did not achieve an SVR.

  22. HCV Increases Endothelial Dysfunction in HIV+ PatientsCorrected in Responders to IFN-RBV 183 HIV/HCV+ patients on HAART and 24 healthy controls. 32/187 patients underwent therapy with IFN-RBV for 48 wk. HIV/HCV+ patients had higher levels of sICAM-1 and sVCAM-1 than the healthy controls (P<.05). Non SVR patients had increased sICAM-1 and sVCAM-1 serum levels, whereas SVR patients had significantly decreased sICAM-1 levels (P=.003). Fernández de Castro I, et al. CROI 2010. Abstract #: Q-143

  23. The GESIDA 3603 Team Principal Investigators J Berenguer, J Gonzalez-García Study Coordinators E Barquilla, H Esteban Statistician JM Bellón H. La Paz, Madrid J Alvarez, JR Arribas, I Bernardino, M Mora, F Pascual, JM Peña, E Rodríguez, I Pérez-Valero, F Zamora, J González-García, H. Germans Trias i Pujol, Badalona B Clotet, A Jou, C Tural H. Getafe, Madrid G Gaspar, G Pérez H. Guadalajara, Guadalajara M Rodríguez, ML Montes H. La Fe, Valencia S Cuellar, J López-Aldeguer H. La Princesa, Madrid I Santos, J Sanz H. Móstoles, Madrid C Barros, E Condés Fundación SEIMC-GESIDA, Madrid E Aznar, E Barquilla, H Esteban, B Moyano H. Príncipe de Asturias, Madrid A Arranz, J de Miguel, J Sanz H. Ramón y Cajal, Madrid A Moreno, S Moreno, C Quereda, MA Sanfrutos H. Santa Creu i Sant Pau, Barcelona P Domingo, JM Guardiola H. Severo Ochoa, Madrid M Cervero, JJ Jusdado, R Torre H. Vall d´Hebron, Barcelona M Crespo, E Van den Eynde H. Gregorio Marañón, Madrid JM Bellón, J Cosín, I Gutiérrez, JC López, P Miralles, B Padilla, M Ramírez, M Sánchez-Conde, J Berenguer, H. 12 de Octubre, Madrid MA Hernando, F Pulido, V Rodríguez, R Rubio H. Clinic, Barcelona P Callau, JM Gatel, J Mallolas, JM Miro H. Clínico Univ de Valencia, Valencia A Ferrer, MJ Galindo H. Clínico San Carlos, Madrid MJ Téllez, J Vergas H. Donostia, San Sebastián J Arrizabalaga, JA Iribarren, MA Von Wichmann H. General de Valencia, Valencia E Ortega, L Ortiz

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