title: Efficacy and safety of rilpivirine in treatment-naive, HIV-1-infected patients with hepatitis B virus/hepatitis C virus coinfection enrolled in the Phase III randomized, double-blind ECHO and THRIVE trials.
abstract: OBJECTIVE
  The efficacy and hepatic safety of the non-nucleoside reverse transcriptase inhibitors rilpivirine (TMC278) and efavirenz were compared in treatment-naive, HIV-infected adults with concurrent hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection in the pooled week 48 analysis of the Phase III, double-blind, randomized ECHO (NCT00540449) and THRIVE (NCT00543725) trials.
  
  
  METHODS
  Patients received 25 mg of rilpivirine once daily or 600 mg of efavirenz once daily, plus two nucleoside/nucleotide reverse transcriptase inhibitors. At screening, patients had alanine aminotransferase/aspartate aminotransferase levels ≤5× the upper limit of normal. HBV and HCV status was determined at baseline by HBV surface antigen, HCV antibody and HCV RNA testing.
  
  
  RESULTS
  HBV/HCV coinfection status was known for 670 patients in the rilpivirine group and 665 in the efavirenz group. At baseline, 49 rilpivirine and 63 efavirenz patients [112/1335 (8.4%)] were coinfected with either HBV [55/1357 (4.1%)] or HCV [57/1333 (4.3%)]. The safety analysis included all available data, including beyond week 48. Eight patients seroconverted during the study (rilpivirine: five; efavirenz: three). A higher proportion of patients achieved viral load <50 copies/mL (intent to treat, time to loss of virological response) in the subgroup without HBV/HCV coinfection (rilpivirine: 85.0%; efavirenz: 82.6%) than in the coinfected subgroup (rilpivirine: 73.5%; efavirenz: 79.4%) (rilpivirine, P = 0.04 and efavirenz, P = 0.49, Fisher's exact test). The incidence of hepatic adverse events (AEs) was low in both groups in the overall population (rilpivirine: 5.5% versus efavirenz: 6.6%) and was higher in HBV/HCV-coinfected patients than in those not coinfected (26.7% versus 4.1%, respectively).
  
  
  CONCLUSIONS
  Hepatic AEs were more common and response rates lower in HBV/HCV-coinfected patients treated with rilpivirine or efavirenz than in those who were not coinfected.
authors.affiliation: Chelsea and Westminster Hospital, St Stephen's Centre, London, UK. mark.nelson@chelwest.nhs.uk
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Gerardo
authors.initials: G
authors.lastname: Amaya
authors.forename: Nathan
authors.initials: N
authors.lastname: Clumeck
authors.forename: Clovis
authors.initials: C
authors.lastname: Arns da Cunha
authors.forename: Dushyantha
authors.initials: D
authors.lastname: Jayaweera
authors.forename: Patrice
authors.initials: P
authors.lastname: Junod
authors.forename: Taisheng
authors.initials: T
authors.lastname: Li
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: Marita
authors.initials: M
authors.lastname: Stevens
authors.forename: Annemie
authors.initials: A
authors.lastname: Buelens
authors.forename: Simon
authors.initials: S
authors.lastname: Vanveggel
authors.forename: Katia
authors.initials: K
authors.lastname: Boven
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000480:Alkynes; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001219:Aspartate Aminotransferases / Q000097:blood; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects; D060085:Coinfection / Q000188:drug therapy / Q000821:virology; D003521:Cyclopropanes; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006509:Hepatitis B / Q000188:drug therapy*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006526:Hepatitis C / Q000188:drug therapy*; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000502:physiology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects; D010919:Placebos / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D000068696:Rilpivirine; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000480:Alkynes; D000998:Antiviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D006514:Hepatitis B Surface Antigens; D018937:Hepatitis C Antibodies; D009570:Nitriles; D010919:Placebos; D011743:Pyrimidines; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000068696:Rilpivirine; C098320:efavirenz