title: Progression to advanced liver fibrosis in HIV-HCV-coinfected patients and prioritization of new hepatitis C therapies.
abstract: BACKGROUND
  Because of their high cost, the use of direct-acting antivirals (DAAs) is being restricted by many governments to chronic HCV-infected individuals with advanced liver fibrosis. However, response rates are lower and toxicities more frequent in this subset of patients.
  
  
  METHODS
  All HIV-HCV-coinfected patients followed for at least 3 years at one reference clinic were identified. Liver fibrosis progression (LFP) was defined as a shift from Metavir F0-F2 to F3-F4 estimates (>9.5 KPa) using elastometry.
  
  
  RESULTS
  A total of 527 HIV-HCV-coinfected patients were identified, of whom 344 had F0-F2 at baseline. Pegylated interferon/ribavirin therapy was given to 205 patients with null/mild fibrosis, of whom 92 (44.9%) achieved sustained virological response (SVR). After a mean follow-up of 53 months, LFP occurred in 5.4% SVR, 25.7% non-SVR and 18% untreated patients (P=0.005). In multivariate analysis, only achievement of SVR prevented LFP (adjusted hazard ratio 2.1; 95% CI 1.1, 4.1; P=0.01). In 139 untreated patients, only greater baseline elastometry values predicted LFP in multivariate analysis (adjusted hazard ratio 1.84; 95% CI 1.03, 3.3; P=0.03). The area under the receiver operating characteristic (AUROC) curve was 79%. A discriminant threshold of 7.1 kPa gave 68% sensitivity and 82% specificity.
  
  
  CONCLUSIONS
  In the absence of successful treatment, more than 20% of HIV-HCV-coinfected patients with null/mild liver fibrosis progress to advanced fibrosis within 5 years. Patients with >7.1 kPa (Metavir F2) display the highest risk. Therefore, all coinfected patients with any significant liver fibrosis should be considered as candidates for new DAA-based therapies.
authors: Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
authors: Pablo
authors: P
authors: Labarga
authors: Jose V
authors: JV
authors: Fernández-Montero
authors: Mariola
authors: M
authors: López
authors: Pablo
authors: P
authors: Barreiro
authors: Carmen
authors: C
authors: de Mendoza
authors: Rocío
authors: R
authors: Sierra-Enguita
authors: Ana
authors: A
authors: Treviño
authors: Vincent
authors: V
authors: Soriano
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D060085:Coinfection; D018450:Disease Progression; D054459:Elasticity Imaging Techniques; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents