Disease relevance of indinavir

• Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy [1].
• RESULTS: Suppression of plasma HIV-1 RNA to undetectable levels was achieved in more patients in the group given efavirenz plus nucleoside reverse-transcriptase inhibitors than in the group given indinavir plus nucleoside reverse-transcriptase inhibitors (70 percent vs. 48 percent, P<0.001) [2].
• Paronychia and pyogenic granuloma of the great toes in patients treated with indinavir [3].
• Alopecia associated with indinavir therapy [4].
• Ergotism related to concurrent administration of ergotamine tartrate and indinavir [5].

Psychiatry related information on indinavir

• Indinavir is being studied as a twice daily and once daily regimen with a low dosage of ritonavir as a way to alleviate tolerability, drug interaction and patient compliance/adherence issues [6].
• OBJECTIVE: To report a case of suspected extrapyramidal symptoms (EPS) in a patient initiated on ritonavir and indinavir while taking risperidone for a tic disorder [7].
• Both injection drug abuse and protease inhibitors, such as indinavir, have been shown to be risk factors for thrombosis [8].
• CASE PRESENTATION: We report a case of HIV dementia (MSK stage 3) in a 57 year old antiretroviral na??ve man who was introduced on zidovudine, lamivudine and ritonavir boosted indinavir, and followed with consecutive lumbar punctures before and after two and 15 months after initiation of HAART [9].

High impact information on indinavir

• Images in clinical medicine. Indinavir crystalluria [10].
• A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team [11].
• The increase in CD4 cell counts over the first 24 weeks was greater in the two groups receiving indinavir than in the zidovudine-lamivudine group (P< or =0.01 for each comparison) [1].
• Ritonavir decreases the systemic clearance of indinavir and overcomes the deleterious effect of food on indinavir bioavailability [12].
• Surprisingly, we find that ritonavir, but not indinavir, inhibits osteoclast differentiation in a reversible manner and also abrogates bone resorption by disrupting the osteoclast cytoskeleton, without affecting cell number [13].

Chemical compound and disease context of indinavir

• PATIENTS: 489 patients receiving indinavir, zidovudine, and lamivudine who had 1) a CD4 count of 0.200 x 10(9) cells/L or less after 8 or more weeks of study therapy and 2) plasma HIV-1 RNA measurements obtained at baseline and week 8 [14].
• Whereas saquinavir also competitively inhibits UGT activity, this drug has not been associated with hyperbilirubinemia, most likely because of the higher K(I) (360 microM) and substantially lower therapeutic levels as compared with indinavir [15].
• RESULTS: At week 48, the proportion of subjects in the indinavir, saquinavir, ritonavir, nelfinavir and amprenavir groups with plasma HIV-1 RNA < or = 400 copies/ml was 53, 50, 50, 41 and 56%, respectively, and the proportion with HIV-1 RNA < or = 50 copies/ml was 47, 56, 50, 47, and 44%, respectively (by intent-to-treat analysis) [16].
• DESIGN: Prospective study including 58 treatment-naive subjects who commenced indinavir or nelfinavir and two nucleosides during primary (PHI; n = 28) or chronic HIV-1 infection (CHI; n = 30) [17].
• Short-term treatment with indinavir fails to reduce the glucose requirement in a patient with malignant insulinoma [18].

Biological context of indinavir

• A reduction in indinavir exposure of this magnitude could lead to the development of drug resistance and treatment failure [19].
• L-735,524 is a potent inhibitor of virus replication in cell culture and inhibits the protease-mediated cleavage of the viral precursor polyproteins that results in the production of noninfectious progeny viral particles [20].
• OBJECTIVE: To determine intracellular concentrations of indinavir (IDV) and investigate the relationship between plasma and intracellular IDV pharmacokinetics in HIV-infected patients [21].
• The median (interquartile ranges) for indinavir AUC, Cmax and Cmin were 18.1 (15.3-23.8) mg/l x h, 4.1 (3.6-4.8) mg/l and 0.17 (0.12-0.30) mg/l, respectively [22].
• All PIs, except indinavir, were cytotoxic and inhibited adipogenesis, increased lipolysis and impaired preadipocyte protein synthesis [23].

Anatomical context of indinavir

• Indinavir in cerebrospinal fluid of HIV-1-infected patients [24].
• FINDINGS: Lymph-node biopsy samples showed that focal lymphadenitis after initiation of indinavir resulted from unsuspected local or disseminated Mycobacterium avium complex (MAC) infection [25].
• INTERPRETATION: Our data suggest that some HIV-1-infected patients on indinavir treatment accumulate intra-abdominal fat that may cause abdominal symptoms [26].
• Visceral abdominal-fat accumulation associated with use of indinavir [26].
• Crystalluria and urinary tract abnormalities associated with indinavir [27].

Associations of indinavir with other chemical compounds

• The proportion of patients who achieved a plasma viral load below the level of detection of 400 copies/ml at week 48 was 43% (39/90) in the ritonavir/saquinavir arm and 63% (57/90) in the indinavir arm (P=0.005, I[28]
• CONCLUSIONS: In this population of previously PI-naive subjects, the rate of virological failure and the frequency of resistance mutations at the time of virological failure were comparable in subjects receiving nelfinavir- or indinavir-containing HAART [29].
• ATP binding cassette multidrug transporters limit the anti-HIV activity of zidovudine and indinavir in infected human macrophages [30].
• Amprenavir and indinavir did not affect adipogenesis or lipolysis [31].
• These data demonstrate that indinavir causes acute and reversible changes in whole-body glucose homeostasis in rats and support the contribution of GLUT4 inhibition to the development of insulin resistance in patients treated with PIs [32].

Gene context of indinavir

• In contrast, increases in indinavir anti-HIV activity require the inhibition of both P-gp and MRP1 [30].
• In IDV-treated cells, 50-60 % of the nuclei could not accumulate SREBP-1 [33].
• Change in circulating levels of the chemokines macrophage inflammatory proteins 1 alpha and 11 beta, RANTES, monocyte chemotactic protein-1 and interleukin-16 following treatment of severely immunodeficient HIV-infected individuals with indinavir [34].
• RESULTS: MRP2 efficiently transported saquinavir, ritonavir and indinavir and this transport could be enhanced by probenecid [35].
• Indinavir, a known UGT1A1 inhibitor, was used as a positive control [36].
• The Ki values for indinavir inhibition of UGT1A1 and UGT1A1*6 were 4.1 and 10.7 mumol/l respectively [37].

Analytical, diagnostic and therapeutic context of indinavir

• MAIN OUTCOME MEASURES: At virologic failure (S1 sample) and 6 weeks later (S2 sample), assessment of protease and reverse transcriptase gene mutations, plasma indinavir level, and degree of viral load rebound; pill count during induction and maintenance periods [38].
• Mean random plasma indinavir concentrations in the 2 groups with rebound were similar to those of a control group with sustained viral suppression, although levels below 50 ng/mL were more frequent in the triple-drug group than in the control group (P = .03) [39].
• Indinavir concentrations in hair from patients receiving highly active antiretroviral therapy [40].
• The mean body-mass index of the groups was similar, and patients in the two indinavir groups did not gain a significant amount of weight after starting the drug [26].
• Mass spectrometry and HPLC confirmed that these crystals were composed of indinavir [27].

References