Research article

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

Carlo Torti¹ , Giuseppe Lapadula¹ , Salvatore Casari¹ , Massimo Puoti¹ , Mark Nelson² , Eugenia Quiros-Roldan¹ , Daniele Bella³ , Giuseppe Pastore⁴ , Nicoletta Ladisa⁴ , Lorenzo Minoli⁵ , Giovanni Sotgiu⁵ , Francesco Mazzotta⁶ , Sergio Lo Caputo⁶ , Giovanni Di Perri⁷ , Gaetano Filice⁸ , Carmine Tinelli⁹ , Giampiero Carosi¹ and the EPOKA-MASTER Study Group

¹  Istituto di Malattie Infettive e Tropicali, Università degli Studi di Brescia, P.le Spedali Civili 1, Brescia, Italy

²  St. Stephen Centre, Chelsea-Westminster Hospital, 369 Fulham Road, London, UK

³  I Divisione Malattie Infettive, Spedali Civili di Brescia, P.le Spedali Civili 1, Brescia, Italy

⁴  Clinica di Malattie Infettive, Policlinico di Bari, P.za Giulio Cesare 1, Bari, Italy

⁵  Istituto di Clinica delle Malattie Infettive, IRCCS S. Matteo, Viale Golgi 2, Pavia, Italy

⁶  Divisione di Malattie Infettive, Ospedale SM Annunziata, Via dell'Antella 58, Firenze, Italy

⁷  Divisione Clinicizzata di Malattie Infettive e Tropicali, IRCCS S. Matteo, Viale Golgi 2, Pavia, Italy

⁸  Istituto di Malattie Infettive, Ospedale Amedeo di Savoia, C.so Svizzera 121, Torino, Italy

⁹  Servizio di Biometria ed Epidemiologia Clinica, IRCCS S. Matteo, Viale Golgi 2, Pavia, Italy

author email corresponding author email

BMC Infectious Diseases 2005, 5:58doi:10.1186/1471-2334-5-58

Published:	14 July 2005

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 ≥III hepatotoxicity (as by ACTG classification) was the primary outcome. Secondary outcome was time to grade IV hepatotoxicity.

Results

Incidence of grade ≥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 ≥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.

Conclusion

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.