The use of pharmacokinetically guided indinavir dose reductions in the management of indinavir-associated renal toxicity.
OBJECTIVE
Indinavir is associated with nephrotoxicity. Therapeutic drug monitoring of indinavir improves clinical outcome, but there is little data regarding therapeutic drug monitoring for patients with established indinavir-associated renal impairment. We prospectively studied the use of therapeutic drug monitoring in patients with virological success but established nephrotoxicity on an indinavir-containing regimen.


METHODS
We measured indinavir C(trough)/C(2h), serum creatinine, pyuria, blood pressure (BP), weight and HIV RNA. The major endpoint of interest was the number of patients achieving a normal creatinine level 20 weeks following final indinavir dose adjustment. Primary analysis was by intention to treat (ITT).


RESULTS
A total of 35 patients were enrolled; mean (SD) age 40.3 (5.8) years; mean (SD) BMI 21.5 (2.8) kg/m(2). At baseline 6/35 (17%) had a serum creatinine concentration within normal limits, but were offered enrolment because of previous nephrotoxicity (nephrolithiasis and/or abnormal serum creatinine), and a screening pharmacokinetic profile associated with increased nephrotoxicity risk. By ITT analysis 11/35 (31%) had normal creatinine at study end (P = 0.18). Of the 29 patients with abnormal creatinine at baseline, 7/29 (24.1%) had normal creatinine at study end (P = 0.016). Patients had a median (IQR) indinavir per dose adjustment over the study of 400 (400-800) mg. We observed improvements in estimated creatinine clearance, pyuria, resting BP and indinavir pharmacokinetic profile. HIV RNA control was maintained with continued immune recovery despite lower indinavir doses.


CONCLUSIONS
Patients experiencing nephrotoxicity on an indinavir-containing regimen were safely maintained on indinavir by means of therapeutic drug monitoring. Parameters of renal function improved but did not return to baseline values, at least in the short-term.
Boyd
Mark A
MA
HIV Netherlands Australia Thailand Research Collaboration, The Thai Red Cross AIDS Research Centre Bangkok, Thailand. mark.boyd@fmc.sa.gov.au
Siangphoe
Umaporn
U
Ruxrungtham
Kiat
K
Reiss
Peter
P
Mahanontharit
Apicha
A
Lange
Joep M A
JM
Phanuphak
Praphan
P
Cooper
David A
DA
Burger
David M
DM
D000328:Adult; D001774:Blood Chemical Analysis; D001794:Blood Pressure; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011776:Pyuria; D012367:RNA, Viral / Q000097:blood; D013785:Thailand
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019469:Indinavir; D003404:Creatinine