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At least 271 records · Page 15Linked to original sources
PubMed2001

Stable or increasing bone mineral density in HIV-infected patients treated with nelfinavir or indinavir.

BACKGROUND AND OBJECTIVES: To determine the factors contributing to changes in bone mineral density (BMD) over time in HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: Analyses of lumbar spine BMD in 183 male Caucasian participants in the Western Australian HIV Cohort study, comprising a longitudinal analysis of data from 54 patients on stable HAART regimens, and a cross-sectional analysis comparing data from 131 protease inhibitor (PI)-treated patients and 52 PI-naive (including 28 antiretroviral treatment-naive) patients. RESULTS: Average lumbar spine BMD remained stable or increased over the time frame considered. Although there was no evidence of a change of average BMD over time in patients receiving nelfinavir (P = 0.92), there was evidence of increasing bone density in the indinavir group (average increase, 0.31 z-score per year; P < 0.001). Lower initial z-scores in the longitudinal analysis were significantly associated with lower pre-HAART BMI (P = 0.003), consistent with results of the cross-sectional analysis in which lowest BMI prior to initial dual X-ray absorptiometry scan was associated with decreased BMD (P = 0.02, overall group). Although PI therapy was also associated with decreased BMD in a univariate analysis of the cross-sectional data (P = 0.04), this effect was abrogated in a multiple linear regression analysis (P = 0.11) with lowest BMI remaining significant (P = 0.04). CONCLUSIONS: We found no evidence, overall, of accelerated bone loss in patients treated with nelfinavir- or indinavir-containing HAART regimens, and propose that indinavir therapy may be associated with an increase in bone mineral density over time. Pre-HAART BMI was an independent and powerful determinant of an individual's initial z-score in the longitudinal analysis, and adjustment for this effect in a cross-sectional analysis abrogated the association between PI therapy and decreased lumbar spine z-score.

Body Mass Index↗
PubMed2001

Drug resistance in patients experiencing early virological failure under a triple combination including indinavir.

OBJECTIVE: To assess the pattern of drug resistance mutations selected in HIV-1-infected patients failing a first line triple combination therapy including indinavir. PATIENTS AND METHODS: Plasma samples from 87 patients collected at the time of the first virological rebound (> 50 HIV-RNA copies/ml) were examined for the presence of drug-resistant genotypes. RESULTS: The mean level of plasma viraemia at rebound was 7824 HIV-1 RNA copies/ml in 73 subjects with good compliance, whereas it was 359,460 HIV-1 RNA copies/ml in 14 patients who admitted to poor adherence. Genetic sequence analysis yielded results for 51 (70%) of the patients having good adherence. More than half of them (26/51, 51%) carried primary mutations associated with resistance to nucleoside analogues. In contrast, primary protease inhibitor resistance mutations were recognized less frequently (14/51, 27%; P < 0.05). Moreover, in 23 (45%) patients there was no evidence of drug-resistant viruses at all. The most frequent drug-resistant genotypes in the reverse transcriptase gene were at codons 184 (n = 19), 215 (n = 14) and 41 (n = 8), whereas for the protease they were at codons 46 (n = 10), 82 (n = 9) and 90 (n = 7). No resistance genotypes were found among non-compliant patients. CONCLUSION: The overall rate of drug-resistant HIV genotypes was 38% (28/73) in patients with good adherence and who were experiencing a first virological failure under a triple combination regimen including indinavir; resistance to nucleoside analogues was more frequent than resistance to indinavir. Therefore, treatment intensification in those patients without resistance, or a selective substitution of nucleosides in those with resistance limited to these compounds, might be justified.

Adult↗
PubMed2003

Pharmacokinetics of nelfinavir and indinavir in HIV-1-infected pregnant women.

BACKGROUND: Protease inhibitor (PI)-based combination antiretroviral therapy is often indicated for treatment of maternal HIV disease, but little is known about PI pharmacokinetics during pregnancy. Increased cytochrome P450 activity may affect the disposition of PI and decrease drug exposure. METHODS: Steady-state PI pharmacokinetics, measured by the area under the plasma concentration versus time curve (AUC(tau)), were evaluated in women on stable antiretroviral regimens containing nelfinavir (n = 9) or indinavir (n = 4) with or without ritonavir (n = 2) during the second and third trimesters of pregnancy and postpartum. Cytochrome P450 activity was assessed by measuring the urine 6 beta-hydroxycortisol to cortisol ratio (6 beta-OHF/F). RESULTS: AUC(tau) in women on indinavir alone decreased and 6 beta-OHF/F ratios increased during pregnancy compared with postpartum control values (n = 2). Nelfinavir results demonstrated no clear change and were highly variable. CONCLUSIONS: The results for indinavir suggest that metabolic induction occurs during pregnancy, which apparently resolves spontaneously postpartum. This may warrant dosage adjustment during pregnancy. This induction is offset by concomitant use of ritonavir. Nelfinavir results were variable and, therefore, the impact of pregnancy on nelfinavir disposition was not fully determined.

Adult↗
PubMed2004

Indinavir increases glucose production in healthy HIV-negative men.

In the absence of HIV infection, changes in adipose tissue and lipid levels, HIV protease inhibitor therapy increases fasting glucose levels,suggestive of hepatic insulin resistance. After 4 weeks of indinavir treatment in nine HIV-negative healthy men, fasting glucose production and glycogenolysis were significantly increased. During the euglycemic hyperinsulinemic clamp, indinavir blunted the ability of insulin to suppress glucose production. Therefore, indinavir worsens hepatic insulin sensitivity, increasing endogenous glucose production.

Blood Glucose↗
PubMedDate not supplied

Epidural lipomatosis secondary to indinavir in an HIV-positive patient.

A human immunodeficiency virus-positive patient receiving indinavir therapy developed a slowly progressive paraparesis. Magnetic resonance imaging findings were consistent with epidural lipomatosis. On discontinuing indinavir, symptoms gradually remitted. Although indinavir, a protease inhibitor, is known to cause abnormal fat accumulation, to the best of our knowledge this is the first report of epidural lipomatosis.

Adult↗
PubMed2000

Fat redistribution in indinavir-treated patients with HIV infection: A review of postmarketing cases.

CONTEXT: Fat redistribution (FR) occurring alone or in association with hyperlipidemia has been associated with protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors (NRTIs); however, the relationship between FR features, relationship of FR to hyperlipidemia, and pathogenesis of FR is unknown. OBJECTIVE: To characterize the spectrum of FR, assess relationships among FR features, determine trends in occurrence of FR, and determine relationship of FR to hyperlipidemia. DESIGN: Review of postmarketing indinavir reports of FR in Merck & Co. Inc.'s database. SETTING AND PARTICIPANTS: 282 reports of FR among HIV-positive patients taking indinavir submitted through the passive postmarketing system to Merck through February 23, 1998. RESULTS: 282 FR reports were compared across 3 groups: fat accumulation (FA) only, FA with peripheral wasting (FA with PW), and peripheral wasting only (PWO). Of 282 reports, 56% (159 of 282) had FA only, 22% (63 of 282) had FA with PW, and 21% (60 of 282) had PWO. The proportions of reports of PWO was higher in men, whereas the proportion of reports of FA was higher in women. Blood lipids were provided in 93 of 282 reports; were elevated in 69 of 93, and were normal in 24 of 93 reports. Proportions of hyperlipidemia and hypertriglyceridemia reports were significantly higher in the PWO group versus FA only group (p =.024 and.003, respectively) and versus FA with/without PW groups (p =.038 and.005, respectively). Weight gain was more frequently reported in those with FA (100%) or FA with PW (68%), whereas weight loss was usually reported in those with PWO (83%). In all, 98% of patients reporting FR on indinavir for whom a concomitant drug history was available were also taking lamivudine, stavudine, or both. A higher proportion of patients reporting PWO (34 of 60; 56.7%) versus FA (42 of 159; 26.4%) only took both lamivudine and stavudine. CONCLUSIONS: Differences observed from analysis of cases in clinical features, gender, weight change, concomitant medications, and presence of hyperlipidemia among the three groups of FR cases reported to Merck suggests that PWO may be a distinct entity from other features of FR. The data suggest that certain antiretroviral combinations predispose HIV persons to development of FR.

Adipose Tissue↗
PubMed2000

Human immunodeficiency virus type 1 population bottleneck during indinavir therapy causes a genetic drift in the env quasispecies.

The impact of emergence of genetic resistance, soon after the beginning of antiretroviral therapy, on the genotype of other viral loci not implicated in the development of resistance was studied in four human immunodeficiency type 1 (HIV-1)-infected patients subjected to indinavir monotherapy. Two patients were chosen because they showed no decrease in virus load during the study period and two were selected because they showed a rapid decline in plasma viraemia after the initiation of therapy and a virus rebound after 12 weeks of treatment. The evolution of virus sequences was analysed within the four infected patients by examining virus sequences spanning the protease and C2-V3 env genes by RT-PCR of plasma samples obtained at the beginning and after 12 weeks of therapy. PCR products from the two genomic regions from the two sample points per patient were cloned and 10-15 clones from each sample were sequenced. Genotypic indinavir resistance was present in the four patients after 12 weeks of therapy. The overall protease and C2-V3 env regions quasispecies diversity at time zero was higher than that after 12 weeks of therapy, but this difference was more significant in the two patients who showed a reduction in virus load soon after the initiation of treatment. C2-V3 env sequences indicated that changes during emergence of resistance to indinavir were only detected in the two patients who showed a drastic reduction in virus load. Thus, a temporal relationship was observed between the start of therapy, a drastic reduction in virus load and a drift in the HIV-1 env quasispecies.

Amino Acid Sequence↗
PubMed2004

Differential diffusions of indinavir and lopinavir in genital secretions of human immunodeficiency virus-infected women.

Plasma and cervicovaginal secretion (CVS) samples were collected from 19 human immunodeficiency virus type 1-infected women on lopinavir- or indinavir-containing regimens. Lopinavir and indinavir were detectable in 29 and 93% of CVS samples, respectively, a finding that may be ascribed to these drugs' differences in protein binding and pK(a). The relationship between lopinavir and indinavir pharmacodynamics and viral evolution in the female genital tract should be assessed over time.

Adult↗
PubMed2004

Pharmacokinetics of indinavir combined with low-dose ritonavir in human immunodeficiency virus type 1-infected children.

So far, no pediatric doses for indinavir combined with ritonavir have been defined. This study evaluated the pharmacokinetics of 400 mg of indinavir/m(2) combined with 125 mg of ritonavir/m(2) every 12 h (q12h) in 14 human immunodeficiency virus type 1-infected children. The area under the concentration-time curve from 0 to 24 h and the minimum concentration of drug in serum for indinavir were similar to those for 800 mg of indinavir-100 mg of ritonavir q12h in adults, while the maximum concentration of drug in serum was slightly decreased, with geometric mean ratios (90% confidence intervals in parentheses) of 1.1 (0.87 to 1.3), 0.96 (0.60 to 1.5), and 0.80 (0.68 to 0.94), respectively.

Adult↗
PubMed2005

A pilot, double-blind, placebo-controlled trial of indinavir in patients with ALS.

There is some evidence of retroviral infection in ALS. A randomized, double-blind, placebo-controlled trial of indinavir in ALS was performed to assess safety and efficacy trends. Nephrolithiasis and gastrointestinal side effects were frequent with indinavir treatment. Group differences in the rate of decline were not significant between the groups for the ALS Functional Rating Scale (p = 0.36) or for the secondary variables. The toxicity and negative efficacy trends discourage further indinavir trials in ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2004

Changes in thrombolytic and inflammatory markers after initiation of indinavir- or amprenavir-based antiretroviral therapy.

HIV-infected subjects who have lipodystrophy and insulin resistance on prolonged antiretroviral therapy have elevated levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) antigens, markers of impaired thrombolysis that are associated with hyperinsulinemia and increased cardiovascular risk. We studied HIV-infected, protease inhibitor (PI)-naive adults treated with indinavir (n = 11) or amprenavir (n = 14) plus two nucleoside reverse transcriptase inhibitors enrolled in two independent prospective trials. Antiretroviral and immune responses were similar in both studies. Over 8 wk, indinavir was associated with decreased insulin sensitivity, whereas amprenavir was not. Levels of tPA antigen declined by approx 25% with both treatments (p < 0.05 for each); levels of PAI-1 antigen did not change. Levels of the inflammatory marker soluble tumor necrosis factor-alpha receptor II (sTNFr2) correlated positively with tPA antigen (r = 0.33, p = 0.02), and mean (SD) plasma concentrations of sTNFr also declined with treatment (4.44 +/- 1.11 ng/mL pretherapy, 3.75 +/- 1.21 posttherapy, p = 0.007). Short-term improvement in a marker of impaired thrombolysis and increased vascular risk can occur during PI-based antiretroviral therapy, perhaps as a consequence of improvement in HIV-related inflammation. This improvement occurred independent of development of insulin resistance, which occurred only with indinavir.

Adult↗
PubMed2001

Economic analysis of initial HIV treatment. Efavirenz- versus indinavir-containing triple therapy.

OBJECTIVE: To compare the clinical and economic outcomes associated with triple therapy containing efavirenz or indinavir and 2 nucleoside reverse transcriptase inhibitors (NRTIs; zidovudine and lamivudine) in HIV-positive patients. DESIGN AND SETTING: An economic model based on viral load and CD4+ cell counts to predict long term outcomes such as progression to AIDS and AIDS-related death was developed and then analysed using data from a randomised clinical trial. Cost estimates from the healthcare system perspective were based on data from 6 state, all-payor databases, the AIDS Cost and Services Utilisation Study, and other literature. Analyses were carried out for time horizons between 5 and 15 years. PATIENTS AND INTERVENTIONS: HIV-positive patients with limited exposure to NRTIs. Initial regimens consisted of efavirenz or indinavir, each combined with 2 NRTIs. A maximum of 2 switches to other regimens was permitted. MAIN OUTCOME MEASURES AND RESULTS: The efavirenz-containing triple therapy regimen was predicted to prolong survival at a savings of up to 10,923 US dollars (1998 values) relative to initial therapy with the indinavir-containing regimen. Patients who receive efavirenz are expected to have 11% greater survival at 5 years and fewer treatment failures (28 vs 52%, at 2 years). Overall, the economic and health benefits predicted for the efavirenz-containing regimen were robust to reasonable variation in key parameters. CONCLUSIONS: The superior clinical trial outcomes for efavirenz-containing regimens should translate into substantial economic and health benefits.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Nonopaque crystal deposition causing ureteric obstruction in patients with HIV undergoing indinavir therapy.

OBJECTIVE: We describe the unique CT features of ureteric calculi in six HIV-infected patients receiving indinavir, the most commonly used HIV protease inhibitor, which is associated with an increased incidence of urolithiasis. CONCLUSION: Ureteric obstruction caused by precipitated indinavir crystals may be difficult to diagnose with unenhanced CT. The calculi are not opaque, and secondary signs of obstruction may be absent or minimal and should be sought carefully. Images may need to be obtained using i.v. contrast material to enable diagnosis of ureteric stones or obstruction in patients with HIV infection who receive indinavir therapy.

Adult↗
PubMed2000

Detection of indinavir crystals in urine: dependence on method of analysis.

OBJECTIVES: To determine the frequency of crystalluria in patients treated with the human immunodeficiency virus protease inhibitor indinavir and to compare methods of detecting crystalluria. METHODS: A total of 308 freshly voided urine specimens from 168 patients treated with indinavir were evaluated by manual microscopy of sediment and microscopy with an automated workstation and by dipstick analysis. RESULTS: Crystals were detected in 22%, 31%, or 32% of specimens using, respectively, an automated workstation, manual microscopy, or both methods. Proteinuria or hemoglobinuria occurred significantly more often in specimens with (28%) than without (18%) crystals. Frequency of crystalluria was unrelated to specific gravity, but it increased at higher pH. Crystals were detected in 21% of specimens with pH less than 6 and 42% of specimens with pH of 6 or higher. CONCLUSIONS: Crystalluria occurs in more than 30% of urine specimens from patients treated with indinavir, but detection rates vary substantially with method of analysis. Manual microscopy detected crystalluria 41% more often than did an automated workstation.

Crystallization↗
PubMed2000

3-year suppression of HIV viremia with indinavir, zidovudine, and lamivudine.

BACKGROUND: Antiretroviral regimens containing HIV protease inhibitors suppress viremia in HIV-infected patients, but the durability of this effect is not known. OBJECTIVE: To describe the 3-year follow-up of patients randomly assigned to receive indinavir, zidovudine, and lamivudine in an ongoing clinical trial. DESIGN: Open-label extension of a randomized, double-blind study. SETTING: Four clinical research units. PATIENTS: 33 HIV-infected, zidovudine-experienced patients with serum HIV RNA levels of at least 20,000 copies/mL and CD4 counts ranging from 50 to 400 cells/mm3. INTERVENTION: Indinavir, zidovudine, and lamivudine. MEASUREMENTS: Safety assessments, HIV RNA levels, CD4 cell counts, and genotypic analyses. RESULTS: After 3 years of follow-up, 21 of 31 contributing patients (68% [95% CI, 49% to 83%]) had serum viral load levels less than 500 copies/mL. Twenty of 31 (65% [CI, 45% to 80%]) had levels less than 50 copies/mL. The median increase in CD4 count from baseline was 230 cells/mm3 (interquartile range, 150 to 316 cells/mm3). Nephrolithiasis occurred in 12 of 33 patients (36%). CONCLUSION: A three-drug regimen of indinavir, zidovudine, and lamivudine suppressed viremia in two thirds of patients for at least 3 years.

Adult↗
PubMed1999

Indinavir-induced nephropathy.

We report the case of a 38-year-old male who developed renal insufficiency while on the protease inhibitor, indinavir. This patient had an increase in serum creatinine over a period of approximately one year, along with persistently abnormal urinalysis. A renal biopsy was performed and showed marked tubular crystal deposition. The indinavir was discontinued, and after two months the patient's serum creatinine and urinalysis returned to normal. To our knowledge this is the second case of indinavir associated nephropathy.

Adult↗
PubMed1999

Nephrolithiasis on indinavir.

(1) Nephrolithiasis is found in 4-13% of patients treated with indinavir, an HIV protease inhibitor. Most of these stones are composed of indinavir. (2) Outcome is often favourable, with simple passage of the stone, but endoscopic or surgical treatment is sometimes required. (3) Crystalluria seems to be more frequent, but is often asymptomatic. (4) Prevention is based on fluid intake of at least 1.5 litres a day. Indinavir withdrawal may be necessary.

HIV Protease Inhibitors↗