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.
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.
Torti
Carlo
C
Istituto di Malattie Infettive e Tropicali, Università degli Studi di Brescia, P.le Spedali Civili 1, Brescia, Italy. torti.carlo@libero.it
Lapadula
Giuseppe
G
Casari
Salvatore
S
Puoti
Massimo
M
Nelson
Mark
M
Quiros-Roldan
Eugenia
E
Bella
Daniele
D
Pastore
Giuseppe
G
Ladisa
Nicoletta
N
Minoli
Lorenzo
L
Sotgiu
Giovanni
G
Mazzotta
Francesco
F
Lo Caputo
Sergio
S
Di Perri
Giovanni
G
Filice
Gaetano
G
Tinelli
Carmine
C
Carosi
Giampiero
G
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
D019380:Anti-HIV Agents; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase