Liver toxicity of antiretroviral combinations including atazanavir/ritonavir in patients co-infected with HIV and hepatitis viruses: impact of pre-existing liver fibrosis.
OBJECTIVE
To appraise the rate of grade 3-4 transaminase elevations (TEs) and grade 4 total bilirubin elevation (TBE) in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C or hepatitis B virus (HCV or HBV, respectively) who receive atazanavir/ritonavir. Moreover, the relationship between these events and the degree of prior liver fibrosis was evaluated.


METHODS
A cohort of 189 HIV-infected patients, 175 co-infected with HCV, 4 with HBV and 10 with both, receiving atazanavir/ritonavir, was analysed. Baseline liver fibrosis was assessed in 113 (60%) patients. Twenty-four patients had cirrhosis, whereas such a diagnosis was ruled out in 58 patients.


RESULTS
Twelve (6%) and 28 (15%) patients developed grade 3-4 TEs and grade 4 TBE, respectively. Eight (10%) of 84 patients with fibrosis >/=F2 versus 1 of 29 (3%) with F0-F1 (P = 0.51) developed grade 3-4 TEs. The frequencies of grade 3-4 TEs in patients with and without cirrhosis were 8% and 5% (P = 0.63), respectively. Grade 4 TBE was more common among patients with cirrhosis (35% versus 13%, P = 0.05) in the univariate analysis. In the multivariate study, the only predictor of grade 3-4 TEs was baseline CD4 cell count <300 cells/mm(3) [adjusted OR (AOR) (95% CI) = 8.77 (1.07-71.42), P = 0.04]. The factors independently associated with grade 4 TBE were baseline total bilirubin >1 mg/dL [AOR (95% CI) = 3.2 (1.21-8.45), P = 0.01] and age >40 years [AOR (95% CI) = 2.98 (1.19-7.47), P = 0.02].


CONCLUSIONS
Prior significant liver fibrosis or cirrhosis do not increase substantially the risk of severe TE associated with atazanavir/ritonavir in patients co-infected with HIV and hepatitis viruses.
Pineda
J A
JA
Unidad de Enfermedades Infecciosas, Hospital Universitario de Valme, Seville, Spain. japineda@telefonica.net
Santos
J
J
Rivero
A
A
Abdel-Kader
L
L
Palacios
R
R
Camacho
A
A
Lozano
F
F
Macías
J
J
D000328:Adult; D000367:Age Factors; D000069446:Atazanavir Sulfate; D001663:Bilirubin / Q000097:blood; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000633:toxicity*; D006509:Hepatitis B / Q000150:complications*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D009842:Oligopeptides / Q000633:toxicity*; D011725:Pyridines / Q000633:toxicity*; D019438:Ritonavir / Q000633:toxicity*; D000637:Transaminases / Q000097:blood
D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D000637:Transaminases; D019438:Ritonavir; D001663:Bilirubin