title: Incidence and risk factors for liver enzyme elevation during highly active antiretroviral therapy in HIV-HCV co-infected patients: results from the Italian EPOKA-MASTER Cohort.
abstract: BACKGROUND
  The risk of hepatotoxicity associated with different highly active antiretroviral therapy (HAART) regimens (containing multiple-protease inhibitors, single-protease inhibitors or non nucleoside reverse transcriptase inhibitors) in HIV-HCV co-infected patients has not been fully assessed.
  
  
  METHODS
  Retrospective analysis of a prospective cohort of 1,038 HIV-HCV co-infected patients who commenced a new HAART in the Italian MASTER database. Patients were stratified into naïve and experienced to antiretroviral therapy before starting the study regimens. Time to grade > or =III hepatotoxicity (as by ACTG classification) was the primary outcome. Secondary outcome was time to grade IV hepatotoxicity.
  
  
  RESULTS
  Incidence of grade > or =III hepatotoxicity was 17.71 per 100 patient-years (p-yr) of follow up in naïve patient group and 8.22 per 100 p-yrs in experienced group (grade IV: 4.13 per 100 p-yrs and 1.08 per 100 p-yrs, respectively). In the latter group, the only independent factors associated with shorter time to the event at proportional hazards regression model were: previous liver transaminase elevations to grade > or =III, higher baseline alanine amino-transferase values, and use of a non nucleoside reverse transcriptase inhibitor based regimen. In the naive group, baseline aspartate transaminase level was associated with the primary outcome.
  
  
  CONCLUSIONS
  Use of a single or multiple protease inhibitor based regimen was not associated with risk of hepatotoxicity in either naïve or experienced patient groups to a statistically significant extent. A cautious approach with strict monitoring should be applied in HIV-HCV co-infected experienced patients with previous liver transaminase elevations, higher baseline alanine amino-transferase values and who receive regimens containing non nucleoside reverse transcriptase inhibitors.
authors: Istituto di Malattie Infettive e Tropicali, Università degli Studi di Brescia, P.le Spedali Civili 1, Brescia, Italy. torti.carlo@libero.it
authors: Carlo
authors: C
authors: Torti
authors: Giuseppe
authors: G
authors: Lapadula
authors: Salvatore
authors: S
authors: Casari
authors: Massimo
authors: M
authors: Puoti
authors: Mark
authors: M
authors: Nelson
authors: Eugenia
authors: E
authors: Quiros-Roldan
authors: Daniele
authors: D
authors: Bella
authors: Giuseppe
authors: G
authors: Pastore
authors: Nicoletta
authors: N
authors: Ladisa
authors: Lorenzo
authors: L
authors: Minoli
authors: Giovanni
authors: G
authors: Sotgiu
authors: Francesco
authors: F
authors: Mazzotta
authors: Sergio
authors: S
authors: Lo Caputo
authors: Giovanni
authors: G
authors: Di Perri
authors: Gaetano
authors: G
authors: Filice
authors: Carmine
authors: C
authors: Tinelli
authors: Giampiero
authors: G
authors: Carosi
mesh_terms: D000328:Adult; D000410:Alanine Transaminase; D019380:Anti-HIV Agents / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001219:Aspartate Aminotransferases; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D015331:Cohort Studies; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D015994:Incidence; D007558:Italy; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008111:Liver Function Tests; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D019380:Anti-HIV Agents; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase