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INTRODUCTION: In general, HIV co-infected patients included in clinical trials evaluating the hepatitis C virus (HCV) therapy with telaprevir (TVR) or boceprevir (BOC) with advanced fibrosis, are scarce. We analyze data concerning the use of these drugs in a real-life clinical setting with patients affected by a more advanced degree of fibrosis in a Spanish cohort. METHODS: We evaluated safety and efficacy in an interim analysis encompassing the first 24 weeks of triple therapy with peginterferon (alfa-2a or alfa-2b), ribavirin and TVR or BOC in an observational, multicentre study. HIV/HCV genotype 1 co-infected patients beginning therapy from January 2012 to July 2013 were included. RESULTS: Enrolled patients were 155 (144 patients on TVR and 11 on BOC), average age was 47 years, 83% were male. With respect to HCV treatment, 44% were naïve, 13% relapsers, 17% partial responders, 21% null responders, and in seven patients, the previous response was unknown. All but three (98%) were under antiretroviral therapy (ART) (other than reverse transcriptase inhibitors, the backbone was raltegravir 43%, atazanavir 35%, and etravirine 28%). Median HCV-RNA at baseline was 6.1 log10, 54% were cirrhotic and 38% F3. At week 4, 93% of patients continued on therapy, 81% at w12, and 73% at w24. Virological failure was observed more frequently in: cirrhotic patients (19% [95% CI, 11-27]) vs F3 (12% [CI, 4-20]); patients with TT allele of the IL28B polymorphism (40% [CI, 18-61]) vs CT (21% [CI, 12-31]), or CC (2,2% [CI, -2-6]); previous null responders (37.5% [CI, 21-54]) vs partial responders (15.4% [CI, 1-29]), naïve (13% [CI, 5-21]) or relapsers (0% [CI, 0-0]); and in patients with a genotype subtype 1a (23.6% [CI, 57-76]) vs 1b (8.1% [CI, -1-17]). Overall, 17% had virological failure and in 8% treatment was discontinued due to adverse events. Severe adverse events occurred in 30 patients (19%). Haematologic disorders were the most common type including severe anaemia in 12 (7.7%) patients. Erythropoietin was employed in 41 patients (26.4%) and 11 (7.1%) received blood transfusions. Nineteen patients (12.2%) were treated with G-CSF, and 17 (11%) with thrombopoietin-receptor agonists. Five patients died (3.2%), three due to hepatic decompensation, one due to pneumonia and one due to pulmonary hypertension. CONCLUSIONS: In a real-life setting, therapy against HCV in co-infected patients with advanced liver fibrosis shows high virologic success at 24 weeks. However, frequent haematologic disorders are observed and a close monitoring and an intensive therapy are needed to optimize the results.
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INTRODUCTION: The fibrogenesis analysis in quimeric CCR1 and CCR5 mice revealed that CCR5 mediates its pro-fibrogenic effects in hepatic cells and promoting stellate cells. The blockage of co-receptors could preserve the progression of hepatic fibrosis in HIV/HCV co-infected patients. OBJECTIVE: To evaluate the beneficial effects on hepatic fibrosis in HIV/HCV co-infected patients that are on antiretroviral therapy (ART) with CCR5 co-receptor antagonists. METHOD AND MATERIALS: A multicentre, retrospective pilot study of the evaluation of hepatic fibrosis at mid- and long-term by non-invasive methods in a HIV/HCV co-infected patients cohort in the Valencian Community (Spain) that received ART with a CCR5 co-receptor antagonist. The cut-off points of serum marker tests of hepatic fibrosis were: AST to Platelet Ratio Index (APRI)<0.5 (F0-F1); >1.5 F2; >2 Cirrhosis and Forns Index<4.2 excludes fibrosis; >6.9>F2 fibrosis. Inclusion criteria was established for HIV/HCV co-infected patients on ART with CCR5 co-receptor antagonists that had no previous history of interferon and ribavirin treatment or those who were null-responders and received CCR5 co-receptor antagonist treatment in the previous year. Patients with HBV infection were excluded. RESULTS: A total of 71 male patients (69%) were reported. A CD4 nadir <100 cells/uL was observed in 42% of patients and 62% (44/71) had a basal CD4 level >350 cells/uL. According to genotypes, 50% were G-1a, 14% G-1b, 11% G-3 and 25% G-4. The median duration of treatment with Maraviroc (MVC) was the following: 45% took it over a year, 41% over two years and 14% over three years. Before starting treatment with MVC, we observed an initial fibrosis of F0-F1 in 49% of patients, F2-F3 in 24% and F4 in 27%. The medium follow-up was of 18.45 months. Progression to a higher fibrosis level was observed in five patients, 11 patients improved at least one stage and the others were stable over time. There were 38 patients taking MVC over two years, 27 patients in this group (59.38%) did not modify their fibrosis, 3 patients (11%) progressed and 8 (29.62%) showed regression of liver fibrosis in one stage. CONCLUSIONS: The data above shows a benefit over fibrosis progression with MVC, expressed by fibrosis serum marker tests in HIV/HCV co-infected patients with CCR5 tropism. The prolong treatment with MVC (over two years) has a better effect on liver fibrosis.
