Increased Incidence of Indinavir Nephrolithiasis in Patients with Hepatitis B or C Virus Infection

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Abstract
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-treated patients were randomly selected as controls. The characteristics of cases and controls were compared by analysis of variance for quantitative parameters and by Fisher's exact test for classes. Results: We observed a significant increase in the incidence of nephrolithiasis 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 significant differences were demonstrated between cases and controls with regard to age (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), duration of indinavir treatment (16.1±5.8 versus 14.1±5.4 months), AST increase ≥1.25 of normal (29.6 versus 25.9%), or ALT increase ≥1.25 of normal (33.3 versus 22.4%). In co-infected patients, ALT increase (≥1.25 of normal), but not AST increase, at the time of indinavir initiation was statistically related to the occurrence of nephrolithiasis. Conclusions: We found a significant increase of nephrolithiasis incidence in patients co-infected with HIV-1 and HCV or HBV, which suggests that underlying multifactorial hepatic damage may limit liver catabolism of indinavir, and consequently increase its renal excretion and the risk of nephrolithiasis. Caution is therefore advised when initiating indinavir treatment in HIV patients with evidence of HBV or HCV infection.