Journal of Antimicrobial Chemotherapy (2001) 48, 355-360
© 2001 The British Society for Antimicrobial Chemotherapy
Incidence and risk factors for the development of indinavir-associated renal complications
a Academic Department of HIV/GU Medicine, The Guy's, King's and St Thomas' School of Medicine, Weston Education Centre, Cutcombe Road, King's College Hospital, London SE5 9RT; b St Stephen's Centre, Chelsea & Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK
Objectives: To describe the incidence and risk factors for the development of indinavirassociated renal complications (IRC), and subsequent clinical outcome.
Patients and methods: This was a retrospective cohort study based on two large HIV centres in London. Eligible patients received indinavir for at least 1 week between 1 December 1995 and 28 February 1999. Development of IRC was ascertained by case-note review. Multivariate logistic regression and Cox Proportional Hazard's model analysis were used to determine independent risk factors for the development of IRC.
Results: 781 patients were eligible. Median CD4 count and viral load at indinavir initiation were 117 x 106 cells/L and 47 332 copies/mL, respectively. Median indinavir exposure was 53 weeks (IQR: 20–83). Many patients received other potentially nephrotoxic drugs during indinavir treatment: co-trimoxazole (46%), aciclovir (33%) or both (20%). Overall IRC incidence was 7.3% (6.7 per 100 person-years indinavir exposure). Cases presented with loin pain (58%), renal colic (42%) or dysuria (19%). Identified precipitating events (26%) included fluid depletion or altered indinavir regimen. In the majority of cases indinavir therapy was continued and there was no progressive rise in creatinine levels. In the multivariate analysis, for indinavir treatment >74 weeks there was a reduced risk of developing IRC (OR = 0.23, 95% CI 0.09–0.57, P = 0.001). Concomitant aciclovir increased the IRC risk (OR = 1.99, 95% CI 1.14–3.51, P = 0.016). Factors not associated with outcome were age, gender, ethnicity, baseline CD4 count and viral load, concomitant co-trimoxazole, or use of specific antiretrovirals.
Conclusion: An overall IRC incidence of 7.3% was identified. Concomitant aciclovir doubled the risk of IRC and we therefore recommend careful monitoring when prescribing aciclovir with indinavir. A precipitating event was identified in 26% of IRC cases, many of which could have been avoided.
* Corresponding author. Tel: +44-20-7848-5770; Fax: +44-20-7848-5769; E-mail: philippa.easterbrook{at}kcl.ac.uk
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