Increased incidence of indinavir nephrolithiasis in patients with hepatitis B or C virus infection

Materials and Methods: A HIV-1 patient database was scanned in March 1998, and 750 patients were identified who had received HAART including indinavir . Of these, 28 cases had nephrolithiasis; and 85 asymptomatic indinavir-tre ated patients were randomly selected as controls. The characteristics of ca ses and controls were compared by analysis of variance for quantitative par ameters and by Fisher's exact test for classes. Results: We observed a significant increase in the incidence of nephrolithi asis in patients co-infected with HIV-1 and either hepatitis C virus (HCV) (HCV RNA-positive) or hepatitis B virus (HBV) (HBs antigen-positive) (odds ratio and 95% confidence intervals: 2.8 and 1.1-7.7), whereas no significan t differences were demonstrated between cases and controls with regard to a ge (42.4+/-8.0 versus 39.8+/-9.8 years), sex (male patients 70.4 versus 74. 1%), duration of HIV-1 infection (8.6+/-3.1 versus 7.7+/-4.0 years), durati on of indinavir treatment (16.1+/-5.8 versus 14.1+/-5.4 months), AST increa se greater than or equal to 1.25 of normal (29.6 versus 25.9%), or ALT incr ease greater than or equal to 1.25 of normal (33.3 versus 22.4%). In co-inf ected patients, ALT increase (greater than or equal to 1.25 of normal), but not AST increase, at the time of indinavir initiation was statistically re lated to the occurrence of nephrolithiasis. Conclusions: We found a significant increase of nephrolithiasis incidence i n patients co-infected with HIV-1 and HCV or HBV, which suggests that under lying multifactorial hepatic damage may limit liver catabolism of indinavir , and consequently increase its renal excretion and the risk of nephrolithi asis. Caution is therefore advised when initiating indinavir treatment in H IV patients with evidence of HBV or HCV infection.