Search

Background Longitudinal assessment of liver fibrosis with transient elastometry (TE) in patients with chronic viral hepatitis is becoming routine clinical practice in many clinics, as this procedure is non-invasive, easy to perform and relatively inexpensive, allowing early detection of cirrhosis. Herein, we examine the incidence of cirrhosis, using TE assessment, in HIV-infected individuals with chronic hepatitis B or C receiving highly active anti-retroviral therapy (HAART). Methods A longitudinal study was performed on a cohort of HIV-infected patients with chronic hepatitis B or C who were followed since 2004 at Hospital Carlos III (Madrid, Spain) with periodic TE assessments. The primary outcome was the development of cirrhosis, defined as liver stiffness >12.5 KPa. Results A total of 508 HIV-infected patients were examined, of whom 54 developed liver cirrhosis during a mean ±sd follow-up of 2.6 ±1.0 years (overall incidence was 41.13 cases per 1,000 person-years). The risk of developing cirrhosis was significantly higher in 297 HCV-RNA-positive patients (either untreated or non- responders to hepatitis C therapy) compared with 55 patients who had cleared HCV with therapy (odds ratio 3.73, 95% confidence interval 1.06–13.17; P=0.04). By contrast, the risk of developing cirrhosis was low and similar in 24 HIV–HBV-coinfected patients under long-term suppressive HBV therapy (mainly tenofovir disoproxil fumarate), 132 HIV-infected patients without chronic liver disease and those who had cleared HCV with therapy. Conclusions Development of liver cirrhosis in HIV- infected individuals in the HAART era is mainly associated with active HCV coinfection. The risk of developing cirrhosis is negligible in patients who cleared HCV with therapy, as well as in HIV–HBV-coinfected patients on long-term suppressive tenofovir disoproxil fumarate therapy.

Background Direct acting antivirals (DAA) targeting the HCV serine protease and RNA polymerase have recently entered clinical development. Information about primary resistance to these compounds in HIV–HCV-coinfected patients is scarce. Methods All individuals newly diagnosed with HIV-1 at several clinics in Madrid between 2000 and 2010 were tested for serum HCV antibody and HCV RNA. The NS3 protease and NS5B polymerase genes were sequenced in all HCV viraemic patients with genotype 1 (G1). Results From 1,684 individuals newly diagnosed with HIV-1 during the 10-year study period, 141 (8.4%) were positive for serum HCV RNA. Overall, 58% were infected with G1, being 1a in 64.2% of them. Altogether, 62% of G1a and 30% of G1b harboured HCV drug-resistant changes, with the most common being prQ80K ( n=9), prV55A ( n=2), polC316Y/N ( n=3) and polV499A ( n=24). Although no primary resistance mutations were identified for HCV protease inhibitors or nucleoside analogues, mutations C316Y/N and V499A conferring resistance to some non-nucleoside analogues were found in 6% and 51% of G1 patients, respectively. Conclusions Natural DAA resistance-associated mutations are frequently seen in HIV–HCV-coinfected individuals. Changes polV499A and prQ80K seem to be natural polymorphisms and their effect on treatment outcomes warrants further examination. However, drug resistance testing in HCV drug-naive individuals coinfected with HIV currently does not seem to be warranted before using HCV protease inhibitors and nucleoside analogues. More information is needed for HCV non-nucleoside analogues.