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PubMed1999

Trimethoprim/sulfamethoxazole does not affect the steady-state disposition of indinavir.

This study evaluates the safety and potential pharmacokinetic interaction between indinavir and trimethoprim/sulfamethoxazole (TMP/SMZ). In a randomized, three-period crossover fashion, 12 healthy adults received 1 week of indinavir sulfate 400 mg orally every 6 hours with placebo, TMP 160 mg/SMZ 800 mg orally every 12 hours with placebo, and indinavir sulfate with TMP/SMZ. Plasma indinavir, SMZ, and TMP concentrations were determined after the last dose of each treatment period. Concomitant administration resulted in a 17% decrease in geometric mean trough plasma indinavir concentrations (p = 0.032), an 18% increase in geometric mean AUC0-12 h and Cmax TMP values (p = 0.031 and 0.030, respectively), and a 5% increase in geometric mean AUC0-12 h SMZ values (p = 0.039). None of these effects was considered clinically significant. The combination of indinavir sulfate and TMP/SMZ is generally well tolerated, with no clinically significant pharmacokinetic interaction being noted.

Abdominal Pain↗
PubMed2000

Synthesis and anti-HIV activity of prodrugs derived from saquinavir and indinavir.

With a view to improving the pharmacological properties, safety and pharmacokinetic profiles of current protease inhibitors, the synthesis of various acyl-substituted saquinavir and indinavir prodrugs, their in vitro stability with respect to hydrolysis and their anti-HIV (LAI and HTLV IIIB) activity and cytotoxicity in CEM-SS and MT4 cells have been investigated. Hydrolysis of the ester bond and liberation of the active free drug was found to be crucial for HIV inhibition: the faster the hydrolysis, the closer the anti-HIV activity was to that of the respective parent drug. This is the case for most of the C-14-substituted indinavir and saquinavir derivatives (IC50 from 10 to 360 nM for ester half-lives of 90 min to 40 h). Concomitantly, the level of HIV inhibition is very low for the prodrugs for which hydrolysis is very slow. This is the case with the myristoyl or oleyl saquinavir esters, owing to the stable masking of the hydroxyl that is part of the peptidomimetic non-cleavable transition state isostere responsible for the inhibitory potency of saquinavir (and indinavir). In contrast, the anti-HIV activity of the monosubstituted C-8 indinavir prodrugs seems not to be correlated with their resistance to hydrolysis, as expected (the C-8 hydroxyl of indinavir is not involved in the transition state isostere). No cytotoxicity was detected for the indinavir and saquinavir prodrugs for concentrations as high as 10 or even 100 microM, thus indicating promising therapeutic potential.

Anti-HIV Agents↗
PubMed2001

Effect of indinavir on the pharmacokinetics of rifampicin in HIV-infected patients.

Indinavir, an antiretroviral agent, has an influence on the pharmacokinetics of other drugs by acting as an inhibitor of cytochrome P450-mediated drug metabolism. The incidence of tuberculosis has increased dramatically in the past decade because of an epidemic of HIV infection. Rifampicin is still one of the most valuable drugs for the standard treatment of tuberculosis. The objective of this study was to investigate the effects of indinavir on the pharmacokinetics of rifampicin in man. Our study was conducted in eleven HIV-infected patients. All patients received a 600-mg single dose of oral rifampicin on day 1 and 15- and 800-mg oral indinavir three times a day from day 2 to day 15. Rifampicin pharmacokinetic studies were carried out on day 1 and day 15. The results showed that rifampicin concentrations were higher when it was administered with indinavir than when it was administered alone. With concomitant indinavir medication, the mean AUC0-24 of rifampicin was increased by 73%. Therefore, we conclude that indinavir has an inhibitory effect on the metabolism of rifampicin.

Adult↗
PubMed2003

Coadministration of milk thistle and indinavir in healthy subjects.

STUDY OBJECTIVE: To determine if milk thistle (silymarin) alters the pharmacokinetics of indinavir. DESIGN: Sequential crossover trial. SETTING: General clinical research center. SUBJECTS: Ten healthy subjects. INTERVENTION: Indinavir 800 mg 3 times/day was given for four doses on days 1 and 2. Silymarin 160 mg 3 times/day was given on days 3-15. On day 16 and for one dose on day 17, both drugs were given at the same dosages. MEASUREMENTS AND MAIN RESULTS: Indinavir's pharmacokinetic parameters were evaluated at steady state both before and after administration of 14 days of silymarin. Blood samples were collected -0.25, 0.5, 1, 2, 3, 4, and 5 hours after indinavir dosing and assayed by high-performance liquid chromatography. The final pharmacokinetic model had first-order absorption after a lag time, and two compartments with first-order elimination from the central compartment. When given alone and combined with silymarin, respectively, the geometric mean (95% confidence interval [CI]) steady-state indinavir area under the plasma concentration-time curve was 20.7 hr x mg/L (15.3-28.2 hr x mg/L) and 19.4 hr x mg/L (15.8-23.6 hr x mg/L) and the trough plasma concentration was 0.340 mg/L (0.232-0.497 mg/L) and 0.232 mg/L (0.129-0.419 mg/L). CONCLUSION: Silymarin has no apparent effect on indinavir plasma concentrations.

Administration, Oral↗
PubMed2006

Lack of in vivo correlation between indinavir and saquinavir exposure and cytochrome P450 3A phenotype as assessed with oral midazolam as a phenotype probe.

STUDY OBJECTIVE: To investigate a potential correlation between exposure to oral midazolam, a commonly used cytochrome P450 (CYP) 3A probe, and saquinavir and indinavir exposure. DESIGN: Open-label, prospective, pharmacokinetic study. SETTING: Outpatient research center. SUBJECTS: Thirty-six healthy volunteers aged 22-50 years. INTERVENTION: Subjects received a single oral dose of midazolam 8 mg; 4 hours later, blood was drawn to determine their serum midazolam concentrations. Midazolam phenotyping was followed by successive administration of the protease inhibitors indinavir and saquinavir, with blood sampling and pharmacokinetic analyses performed at steady state. MEASUREMENTS AND MAIN RESULTS: Pharmacokinetic parameters of each protease inhibitor were evaluated to assess for a potential relationship with 4-hour concentrations of midazolam. No correlations between phenotype results for midazolam and any pharmacokinetic parameter for indinavir or saquinavir were identified (r(2)=0.00002-0.073). When the results were analyzed based on race, significant correlations were identified in five African-American subjects, including correlations between 4-hour midazolam levels and apparent oral clearance of saquinavir (r(2)=0.734, p=0.064), area under the plasma concentration-time curve from 0-8 hours (r(2)=0.914, p=0.011), minimum concentration (r(2)=0.857, p=0.024), and maximum concentration (r(2)=0.969, p=0.002). These findings for African-American subjects were not seen with indinavir. No correlation was found between indinavir and saquinavir pharmacokinetic parameters (r(2)=0.017-0.261). CONCLUSION: Oral midazolam was not a useful probe for predicting saquinavir or indinavir exposure at steady state. Reasons for the lack of correlation likely included differences between midazolam and protease inhibitor P-glycoprotein specificity, differences in the relative contribution of CYP3A5-mediated metabolism, and/or variation in intestinal and hepatic CYP3A specificity. The strong correlation between midazolam phenotype and pharmacokinetic parameters for saquinavir in African-American subjects indicated a racial difference in one or more of these confounding variables.

Administration, Oral↗
PubMed2001

The HIV protease inhibitor indinavir impairs sterol regulatory element-binding protein-1 intranuclear localization, inhibits preadipocyte differentiation, and induces insulin resistance.

Protease inhibitors used in the treatment of HIV infection have been causally associated with lipodystrophy and insulin resistance and were shown to alter adipocyte differentiation in cultured cells. We aimed to delineate the mechanism by which indinavir impaired adipocyte function. We report that indinavir altered neither the growth nor insulin sensitivity of 3T3-F442A preadipocytes, nor did it alter the initial step of their differentiation, i.e., clonal proliferation. However, adipose conversion was inhibited by indinavir (by 50-60%), as shown by 1) the decrease in the number of newly formed adipocytes; 2) the lower level of the adipogenic protein markers, sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and the insulin receptor (IR); and 3) the lack of SREBP-1 and PPAR-gamma immunoreactivity in the nucleus of most indinavir-treated cells. Partial adipose conversion also correlated with an accumulation of SREBP-1 at the nuclear periphery and an alteration in its electrophoretic mobility. Defective expression and nuclear localization of PPAR-gamma probably resulted from the decreased level of nuclear SREBP-1. Indinavir also rendered 3T3-F442A adipocytes resistant to insulin for mitogen-activated protein kinase activation at a step distal to IR substrate-1 tyrosine phosphorylation. Hence, indinavir impairs differentiation at an early step of adipose conversion probably involving the process controlling SREBP-1 intranuclear localization.

3T3 Cells↗
PubMed2000

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-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 > or = 1.25 of normal (29.6 versus 25.9%), or ALT increase > or = 1.25 of normal (33.3 versus 22.4%). In co-infected patients, ALT increase (> or = 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.

Adult↗
PubMed1999

The choice of HIV protease inhibitor: indinavir is currently the best option.

(1) Recent consensus recommendations agree that first-line treatment of HIV infection should consist of a three-drug regimen combining a protease inhibitor and two nucleoside reverse transcriptase inhibitors. Some recommendations specifically advise against using the current formulation of saquinavir, but none express a preference for one of the other three protease inhibitors currently marketed in France (indinavir, nelfinavir and ritonavir). (2) These HIV protease inhibitors have established efficacy on viral load and the CD4+ lymphocyte count. Saquinavir may have lower virological efficacy. (3) The clinical efficacy of three-drug regimens containing indinavir or saquinavir is well demonstrated in patients at an advanced stage of HIV disease. (4) The risk of viral resistance is not currently a factor in choosing a HIV protease inhibitors. (5) Several epidemiological studies have compared the risk of adverse effects on three-drug regimens including indinavir, ritonavir or saquinavir. In these studies saquinavir was the best-tolerated drug and ritonavir the worst-tolerated. (6) Ritonavir interacts with many drugs. The poor bioavailability of the current saquinavir formulation also leads to risk of interactions. (7) Treatment constraints differ from one protease inhibitor to another, and these must be taken into account case by case. (8) The daily cost of treatment is not currently an important factor in choosing among the various preparations. (9) Taking into account efficacy, adverse effects, interactions and treatment constraints, the combination of indinavir with two nucleoside reverse transcriptase inhibitors currently seems to be the best choice for the largest number of patients. (10) If problems of compliance arise, nelfinavir can be an alternative to indinavir. (11) In patients at an advanced stage of HIV disease who comply well with their treatment, saquinavir can also be an alternative to indinavir.

Clinical Trials as Topic↗
PubMed1998

[Nephritic colic due to indinavir].

OBJECTIVE: Evaluate the frequency and assess curative and preventive measures against urinary lithiasis in patients treated with indinavir. PATIENTS AND METHODS: Fourteen HIV seropositive patients who developed severe and acute flank pain were included. Four of the patients receiving 800 mg indinavir t.i.d. had fever (38.5 degrees C) or delayed secretion (> 2 h). Delay from indinavir treatment onset was 1 to 321 days. During the same period, 155 patients had been treated with indinavir. Clinical features, radiology and laboratory results were recorded in addition to an analysis of the lithiasis if possible. RESULTS: Transient moderate renal failure occurred in 8 patients. Mean urine pH was 6. Serum phosphorus, calcium, and uric acid, liver tests and urinalysis were normal. A JJ ureteral stent was inserted in 4 cases due to complications. In all cases, fluids, analgesics and antispasmodics provided favorable outcome. Inversely, nonsteroid antiinflammatory drugs given in 2 patients had a deleterious effect on renal function. The lithiasis was eliminated in 3 cases and infrared spectrophotometry demonstrated a structure compatible with indinavir monohydrate. CONCLUSION: The formation of urinary lithiasis is a frequent complication of indinavir therapy (9%). Hyperhydration and urine acidification are usually successful but emergency drainage is required in approximately 3% of cases. Nonsteroidal antiinflammatory drugs should be avoided due to the risk of renal toxicity. A precise evaluation of fluid intake and diet, drug associations and personal history is needed to recognize patients at risk of recurrent lithiasis formation.

Acute Kidney Injury↗
PubMed2000

The HIV-1 protease inhibitor indinavir impairs insulin signalling in HepG2 hepatoma cells.

AIMS/HYPOTHESIS: Patients treated with human immunodeficiency virus-1 protease inhibitors often develop impaired glucose tolerance or diabetes, most likely due to an induction of insulin resistance. We therefore investigated whether the protease inhibitor indinavir alters insulin signalling. METHODS: We incubated HepG2 cells for 48 h without or with indinavir (100 micromol/l). Subsequently 125I-insulin binding to the cells and the effects of insulin stimulation on insulin-receptor substrate-1-phosphorylation, association of phosphatidylinositol 3-kinase with insulin-receptor substrate-1 and Akt-Thr308-phosphorylation were measured. RESULTS: In cells not exposed to indinavir, insulin (100 nmol/l) led to rapid increases of insulin-receptor substrate-1-phosphorylation, association of phosphatidylinositol 3-kinase with insulin-receptor substrate-1 and Akt-phosphorylation during the first 75 s, followed by subsequent decreases. In indinavir-treated cells, these insulin-stimulated increases during the first 75 s were reduced by 30-60% and this was not associated with alterations in cell number or viability, insulin binding to the cells or cellular insulin-receptor substrate-1-content. CONCLUSION/INTERPRETATION: Effects of indinavir on initial insulin signalling could cause, or contribute to, the metabolic effects of human immunodeficiency virus-1 protease inhibitors.

Carcinoma, Hepatocellular↗
PubMed2004

Molecular dynamics simulations of 14 HIV protease mutants in complexes with indinavir.

The molecular mechanisms of HIV drug resistance were studied using molecular dynamics simulations of HIV-1 protease complexes with the clinical inhibitor indinavir. One nanosecond molecular dynamics simulations were run for solvated complexes of indinavir with wild type protease, a control variant and 12 drug resistant mutants. The quality of the simulations was assessed by comparison with crystallographic and inhibition data. Molecular mechanisms that contribute to drug resistance include structural stability and affinity for inhibitor. The mutants showed a range of structural variation from 70 to 140% of the wild type protease. The protease affinity for indinavir was estimated by calculating the averaged molecular mechanics interaction energy. A correlation coefficient of 0.96 was obtained with observed inhibition constants for wild type and four mutants. Based on this good agreement, the trends in binding were predicted for the other mutants and discussed in relation to the clinical data for indinavir resistance. [figure: see text]. Poincare map representation for WT protease-indinavir complex. The side chain of Tyr 59 showing the positions of hydrogen atoms.

Binding Sites↗
PubMed2005

LC-MS/MS determination of the HIV-1 protease inhibitor indinavir in brain and testis of mice.

A rapid and sensitive method for the determination of indinavir in mice brain and testis is described and validation data are provided. Indinavir and the internal standard (IS) amprenavir were isolated from homogenized tissue matrices using a mixed-mode solid-phase extraction (SPE) procedure and were then analyzed by reversed-phase liquid chromatography/tandem mass spectrometry (LC-MS/MS). The mass spectrometer in the positive-ion multiple reaction monitoring mode used pairs of ions at m/z of 614.1/421.3 for indinavir and of 506.1/245.3 for IS. The calibration curves were linear over the range 0.0012-0.0390 micromol/kg for brain and 0.39-12.50 micromol/kg for testis. Linearity, repeatability and accuracy were validated. The applicability of the method was demonstrated by assessing indinavir in brain and testis of three mice dosed with intravenous bolus administration of indinavir (16.3 micromol/kg).

Animals↗
PubMed1999

Effect of indinavir and higher CD4+ T-cell count on viral load response after 6 months of highly active antiretroviral therapy.

This retrospective, unmasked chart review was undertaken to determine which HIV-infected patients receiving protease inhibitors (PIs) for the first time were most likely to experience a decrease in plasma viral load (PVL) and which factors were associated with a PVL < 500 copies/mL below the detectable limits after 6 months. A total of 308 patients aged > 15 years with a PVL > 500 copies/mL received therapy that included a PI in addition to other antiretroviral therapies (128 patients, saquinavir hard-gel capsule 600 mg TID; 107 patients, indinavir 800 mg TID; and 73 patients, ritonavir 600 mg BID). The choice of drug was at individual clinicians' discretion. Patients were followed for a median of 10 (range, 6 to 21) months. Of the 128 patients who received saquinavir, 45% were switched to another PI (33%, indinavir; 12%, ritonavir). Seventy percent of the 73 patients initially given ritonavir were switched (45%, indinavir; 25%, saquinavir), as were 23% of the 107 patients initially given indinavir (15%, saquinavir; 8%, ritonavir). A total of 34.1% (n = 105) of patients achieved a PVL < 500 copies/mL; in 51.6%, PVL decreased > 0.5 log copies/mL. In this subgroup, both treatment-naive patients and those who were receiving a new combination of antiretroviral therapy when they started PI treatment had a more pronounced decline in PVL (P < 0.001). After adjustment by logistic regression analysis for age, sex, mode of transmission, and duration of highly active antiretroviral therapy (HAART), CD4+ cell count and initial type of PI received were independently associated with PVL < 500 copies/mL. In the present study, the treatment success rate was low (34.1%) compared with rates observed in randomized, controlled trials. A higher CD4+ cell count and use of indinavir at the initiation of HAART are associated with a better viral load response.

Adult↗
PubMed2002

Experience of a combination including indinavir 400 mg plus ritonavir 200 mg twice daily in HIV-infected patients: pharmacokinetic data.

Low doses of ritonavir, a strong inhibitor of cytochrome P450 3A4, enhances the pharmacokinetic profile of indinavir with increased serum levels. We assessed the indinavir-ritonavir 400/200 twice daily combination in 17 HIV-infected patients focusing on the pharmacokinetic data and the tolerance of this regimen. IDV trough and peak concentrations were measured by high-performance liquid chromatography. Median indinavir trough and peak concentrations were 553 ng/ml and 3626 ng/ml, respectively. A good tolerance was observed except for three patients who experienced a major toxicity. Only one dose adjustment was related to indinavir toxicity. Considering the fact that Cmax is mainly responsible of the adverse effects, particularly renal stones, the indinavir-ritonavir 400/200 mg twice daily regimen offers a well-tolerated combination with an increased Cmin but a lower Cmax compared with both the standard tid regimen and higher dose of IDV-RTV regimens.

Antiretroviral Therapy, Highly Active↗
PubMed1998

Simple high-performance liquid chromatographic determination of the protease inhibitor indinavir in human plasma.

Indinavir is a member of a class of protease inhibitors that actively prevent the acquired immunodeficiency syndrome virion from maturing. A high-performance liquid chromatographic (HPLC) assay was developed and validated for the determination of indinavir in human plasma. Indinavir and the internal standard were isolated from the plasma by ether extraction. The residue after evaporation of ether was reconstituted with buffer and injected onto a C4 reversed-phase column eluted isocratically with a mobile phase consisting of 35:65 (v/v) of acetonitrile and buffer. A wavelength of 210 nm was found to be optimum for detection. The calibration range of this assay was from 10 to 5000 ng/ml and coefficients of variation for the assay ranged from 4.6% to 11.0% for three different drug concentrations and the limit of quantitation was 10 ng/ml. During the validation, short-term stability of the drug in plasma, stability during heat deactivation and on repeated freezing and thawing of plasma was evaluated. The overall recovery of indinavir by the ether extraction method was 91.4%. This HPLC assay was found to be a simple and reproducible method for monitoring indinavir levels in human plasma obtained during clinical trials of the drug.

Buffers↗
PubMed2000

High-throughput simultaneous determination of the HIV protease inhibitors indinavir and L-756423 in human plasma using semi-automated 96-well solid phase extraction and LC-MS/MS.

A method for the simultaneous determination of the HIV protease inhibitors indinavir and L-756423, in human plasma has been developed. Plasma samples (0.5 ml) were extracted using a 3M Empore 96-well plate in the mixed phase cation exchange (MPC) format. The extraction method was automated through the application of both the Packard 204DT and TOMTEC Quadra 96 work stations, and the resulting extracts were analyzed using a PE-Sciex API-3000 LC-MS/MS with a heated nebulizer interface (500 degrees C). The assay was linear in the concentration range 1-2500 ng/ml for indinavir and 5 2500 ng/ml for L-756423 when 0.5-ml aliquots of plasma were extracted. Recoveries of indinavir and L-756423 were greater than 76 and 80%, respectively, over the calibration curve range when using the described sample preparation method. Within-batch precision and accuracy for the quantitation of indinavir over the range 1-2500 ng/ml were 5.4% R.S.D. or less and within 4.0%, respectively. Within-batch precision and accuracy for the quantitation of L-756423 over the range 5-2500 ng/ml were 5.3% R.S.D. or less and within 3.4%, respectively. Interbatch variability for the analysis of indinavir QC samples at low (3 ng/ml), middle (250 ng/ml) and high (2250 ng/ml) were 3.2, 2.9, and 1.9%, respectively. Interbatch variability for the analysis of L-756423 QC samples at low (15 ng/ml), middle (250 ng/ml) and high (2250 ng/ml) concentration were 2.0, 2.5, and 3.3%, respectively. The validated assay was used in support of human clinical trials.

Anti-HIV Agents↗
PubMed1999

Treatment for human immunodeficiency virus with indinavir may cause relevant urological side-effects, effectively treatable by rehydration.

OBJECTIVE: To explore the occurrence of, and diagnostic and therapeutic procedures for urological side-effects (e.g. micro- and macrohaematuria, and kidney stone formation) in individuals treated with indinavir for the human immunodeficiency virus (HIV). PATIENTS AND METHODS: The study comprised a retrospective follow-up of 74 individuals infected with HIV-1 and who were treated with indinavir orally at a daily dose of 2.4 g. Data were collected at the outpatient department of our institution between March 1996 and November 1997. RESULTS: Of the 74 individuals treated with indinavir, 15 (20%) had indinavir-related urological side-effects (19 episodes), most commonly dull flank pain and dysuria. Microhaematuria occurred in 16 of the 19 episodes. Four patients showed urinary tract distension ultrasonographically as a possible indirect sign of urolithiasis and one patient passed a kidney stone. In four patients treatment had to be stopped permanently, but in the remaining 11 patients treatment was continued. Some patients required dose reduction and/or interruption of treatment; only conservative therapeutic measures were required, consisting of rehydration (fluid intake >1.5 L/day) and analgesics. CONCLUSIONS: Urological side-effects of indinavir may be apparent in 20% of patients so treated; some (5%) may require permanent withdrawal. In addition to a history and clinical examination, urine analysis and ultrasonography were the only diagnostic procedures required. Therapy is mainly conservative, using rehydration, analgesics and a brief discontinuation of therapy, according to the severity of the symptoms.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Indinavir nephropathy revisited: a pattern of insidious renal failure with identifiable risk factors.

Indinavir is a well-known cause of crystal-induced acute renal failure, dysuria and flank pain, and nephrolithiasis. Recently a more insidious tubulointerstitial lesion has been recognized as secondary to the drug. We report a case of a hepatitis C-positive patient on long-term indinavir therapy for human immunodeficiency virus (HIV) who developed a slowly progressive rise in serum creatinine. Renal biopsy revealed a diffuse interstitial infiltrate with numerous eosinophils and scarring. The tubules showed focal necrosis and dilation with elongated crystals present within their lumina. The elevated serum creatinine decreased to a new baseline over several months with the discontinuation of indinavir. We review the literature of renal syndromes associated with indinavir focusing on chronic progressive tubulointerstitial injury and speculate on risk factors and potential mechanisms of indinavir-induced renal injury.

Adult↗