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Nephrotoxicity in patients randomized to Indinavir 800 mg 3x/week or indinavir/ritonavir 800/100 twice per day
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Mark Boyd from HIV-NAT, the Thai Red Cross AIDS Research Center and from NCHER in Australia reported on a substudy comparing urinary tract signs and symptoms (UTSS) and changes in renal function between the 2 arms. He reported 64 week outcome.
164 patients started therapy: 67 males, mean BMI 28 kg/m2, age 35.
In brief, Boyd concluded that-- (1) nephrotoxicity was similar for both arms, (2) female gender, lower BMI (weight), and longer duration of therapy were risk factors for developing UTSS. These results are different from the BEST study and which either kept patients on IDV 3x/day or switched patients from IDV 3x/day to IDV/RTV 800/100 bid. They found patients who switched tended to experience more side effects/toxicities and to discontinue IDV/RTV.
5 patients required drug interruptions due to UTSS (2 in IDV and 3 in IDV/RTV arms‹no real difference seen), but no permanent drug discontinuations occurred.
There are no statistical difference between the two arms in development of indinavir crystalluria (>3 cells/ml). Overall, about 40% of patients had at least one sample positive for indinavir crystalluria. At week 64, 10-20% of patients had indinavir crystalluria.
At week 64, patients receiving IDV 3x/day had more (about 50% vs 33%, p=0.047) leucocyturia (the presence of white blood cells in urine). At weeks 4 and 36 there did not appear to be any differences between the 2 arms in percent of patients with leucocyturia (>3 cells/ml).
There did not appear to be any differences in overall clinical nephrolithiasis (22% bid group [n=50) vs 17% tid group [n=54]) between IDV 3x/day vs IDV/RTV bid (back or flank pain, renal calculi, painful urination and blood in urine).
Females were 2 times more likely to develop leucocyturia (white cells in blood), hematuria (blood in urine), indinavir crystals, and >25% decline in creatinine clearance, using multivariate analysis.
The regimen, BMI, and duration of therapy were not risk factors for developing IDV crystalluria. Only female gender, (editorial note: perhaps this was due to low body weight of Thai females).
BMI, female gender, and duration of therapy were risk factors for developing leucocyturia (white cells in blood).
Female gender and having IDV crystal at week 4 were the only risk factors for developing >25% decline in creatinine clearance.
The results reported from the Danish BEST Study suggest IDV/RTV (800/100 bid) may not be as tolerable as IDV 3x/day. 323 patients in the study had undetectable viral load (<500 copies) on an IDV 3x/day regimen and either stayed on their regimen or switched to IDV/RTV bid while continuing the other drugs in their regimen. After 48 weeks, 74% in the IDV arm vs 58% who switched to the IDV/RTV arm had undetectable viral load, which the study authors suggested was due to increased side effects: GI, kidney stones, elevated cholesterol & triglycerides, and blood in the urine.
The author concluded: (1) nephrotoxicity was similar in both arms; (2) there were significant increases in leucocyturia (presence of white blood cells in urine) over time in the combined group of patients; (3) there was deterioration in renal function in both arms in the first 12 weeks which stabilized afterwards; (4) females were at greater risk for crystals, white cells in blood, and impaired renal function; (5) lower BMI and duration of therapy were associated with leucocyturia; (6) crystalluria was associated with renal impairment; (7) there were no permanent discontinuations but patients had limited options for switching therapy; (8) renal function should be monitored for patients on indinavir.
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