A comparison of stavudine, didanosine and indinavir with zidovudine, lamivudine and indinavir for the initial treatment of HIV-1 infected individuals: Selection of thymidine analog regimen therapy (START II)*

Eron, Joseph J.; Murphy, Robert L.; Peterson, Dolores M.; Pottage, John C.; Parenti, David M.; Jemsek, Joseph G.; Swindells, Susan; Sepulveda, Gladys; Bellos, Nicholaos C.; Rashbaum, Bruce; Esinhart, Jim; Schoellkopf, Nancy; Grosso, Robert; Stevens, Michael R.

doi:10.1097/00002030-200007280-00016

Cited by 74 publications

(31 citation statements)

References 27 publications

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“…LDL-cholesterol and triglyceride levels, compared with subjects receiving zidovudine-lamivudinenelfinavir [22]. Elevations in fasting triglyceride levels were more common in association with stavudine-didanosineindinavir than with zidovudine-lamivudine-indinavir in a published randomized study [23]. The nucleoside reversetranscriptase inhibitor (NRTI) tenofovir was associated with smaller increases in cholesterol and triglycerides levels than was stavudine, as published in a recent abstract [24].…”

Section: Discussionmentioning

confidence: 99%

Metabolic effects associated to the highly active antiretroviral therapy (HAART) in AIDS patients

et al. 2009

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The aim of this study was to evaluate the metabolic abnormalities (dyslipidaemia and insulin resistance) associated with highly active antiretroviral therapy (HAART) in AIDS patients, treated in Campo Grande, Mato Grosso do Sul, Brazil. The patients were distributed in five different groups: Group 1, HIV-infected without antiretroviral therapy; Group 2, with Zidovudine, Lamivudine and Efavirenz or Nevirapine; Group 3, with Zidovudine, Lamivudine and Protease Inhibitor; Group 4, with Stavudine, Lamivudine and Efavirenz or Nevirapine; and Group 5, with Stavudine, Lamivudine and Protease Inhibitor. The lipid and glucose profile were determined and statistics comparison was made. The findings of this study showed significant statistics elevations of total cholesterol and triglycerides levels in patients of Groups 3, 4 and 5, when comparing to patients of Groups 1 and 2. Significant differences were not observed between the groups in the others parameters evaluated: Glucose, HDL cholesterol and LDL cholesterol. Comparing two drugs of same class (NNRTI) through the subgroups II-efavirenz and II-nevirapine, significant differences in the serum levels of total cholesterol, triglycerides and glucose favorable to the subgroup II-NVP were observed. These findings suggest that combinations including Protease Inhibitors and/or Stavudine could cause more adverse metabolic effects, and if possible, should be avoided in patients with others cardiovascular risk factors to prevent the precocious atherosclerosis in AIDS patients receiving HAART.

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Section: Discussionmentioning

confidence: 99%

Metabolic effects associated to the highly active antiretroviral therapy (HAART) in AIDS patients

et al. 2009

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“…In the present study, if the logistic regression analysis had been performed including lopinavir/ritonavir as ritonavir exposure, the adjusted OR for ritonavir would have been 2.23 (95% CI 1.38 -3.61; P ϭ 0.001). The possible role of specific nucleoside analogues to alter lipid profile is not well established; some studies suggest that stavudine may be associated with hypertriglyceridemia and hypercholesterolemia in comparison with other nucleosides or nucleotide analogues (27,28).…”

Section: Methodsmentioning

confidence: 99%

Metabolic Syndrome Among HIV-Infected Patients

et al. 2005

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OBJECTIVE—To assess the prevalence in HIV-infected patients of the metabolic syndrome as defined by the National Cholesterol Education Program, i.e., three or more of the following components: abdominal obesity, hypertriglyceridemia, low HDL cholesterol, high blood pressure, and high fasting glucose. RESEARCH DESIGN AND METHODS—In this cross-sectional study, 710 HIV-infected patients managed at the outpatient clinic of a tertiary hospital during 2003 completed the study protocol consisting of a medical examination and laboratory analysis after a 12-h overnight fast. RESULTS—Metabolic syndrome prevalence was 17% and increased from 5.1% among HIV-infected patients under age 30 years to 27.0% for those aged 50–59 years. Age (per 10-year increment) (odds ratio [OR] 1.41 [95% CI 1.12–1.77]), BMI (1.27 [1.19–1.36]), past and present protease inhibitor exposure (2.96 [1.03–3.55] and 4.18 [1.4–12.5], respectively) were independently associated with the metabolic syndrome on logistic regression analysis. Furthermore, only stavudine (d4T) (1.74 [1.01–2.98]) and lopinavir/ritonavir (2.46 [1.28–4.71]) were associated with the metabolic syndrome after adjustment for age and BMI. CONCLUSIONS—The prevalence of metabolic syndrome among these HIV-infected patients is similar to that previously reported in uninfected individuals. Of specific concern is the association of protease inhibitor exposure with the metabolic syndrome and, more specifically, with exposure to stavudine and lopinavir/ritonavir when individual antiretroviral drugs were analyzed.

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“…In this model the predicted concentration of ritonavir, based on the Bayesian estimates of clearance, volume of distribution and absorption rate constant, was directly related to the elimination of indinavir (1). In the second model, a direct relationship between the clearance of indinavir and the total exposure to ritonavir, expressed as the predicted AUC, was assumed (2).…”

Section: Basic Pharmacokinetic Modelmentioning

confidence: 99%

“…Indinavir is a potent human immunodeficiency virus (HIV) protease inhibitor [1][2][3]. The oral bioavailability of the drug when dosed alone is decreased when administered together with food and therefore indinavir should be taken on an empty stomach [4].…”

Section: Introductionmentioning

confidence: 99%

Population pharmacokinetics of indinavir alone and in combination with ritonavir in HIV‐1‐infected patients

Kappelhoff

Huitema

Sankatsing

et al. 2005

Brit J Clinical Pharma

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AimsThe aim of the study was to characterize the population pharmacokinetics of indinavir, define the relationship between the pharmacokinetics of indinavir and ritonavir, and to identify the factors influencing the pharmacokinetics of indinavir alone or when given with ritonavir.Methods HIV-1-infected patients being treated with an indinavir-containing reg imen were included. During regular visits, 102 blood samples were collected for the determination of plasma indinavir and ritonavir concentrations. Full pharmacokinetic curves were available from 45 patients. Concentrations of indinavir and ritonavir were determined by liquid chromatography coupled with electrospray tandem mass spectrometry. Pharmacokinetic analysis was performed using nonlinear mixed effect modelling (NONMEM). ResultsThe disposition of indinavir was best described by a single compar tment model with first order absorption and elimination. Values for the clearance, volume of distribution and the absorption rate constant were 46.8 l h -1 (24.2% IIV), 82.3 l (24.6% IIV) and 02.62 h -1 , respectively. An absorption lag-time of 0.485 h was detected in patients also taking ritonavir. Furthermore this drug, independent of dose (100-400 mg) or plasma concentration, decreased the clearance of indinavir by 64.6%. In contrast, coadministration of efavirenz or nevirapine increased the clearance of indinavir by 41%, irrespective of the presence or absence of ritonavir. Female patients had a 48% higher apparent bioavailability of indinavir than males. ConclusionsThe pharmacokinetic parameters of indinavir were adequately described by our population model. Female gender and concomitant use of ritonavir and nonnucleoside reverse transcriptase inhibitors strongly influenced the pharmacokinetics of this drug. The results support the concept of ritonavir boosting, maximum inhibition of indinavir metabolized being observed at 100 mg. Pharmacokinetics of indinavirBr J Clin Pharmacol 60 :3 277

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A comparison of stavudine, didanosine and indinavir with zidovudine, lamivudine and indinavir for the initial treatment of HIV-1 infected individuals: Selection of thymidine analog regimen therapy (START II)*

Abstract: The combination of stavudine, ddl and IDV resulted in potent antiretroviral effects over a 48-week period, comparable or superior to zidovudine, 3TC and IDV supporting the use of stavudine, ddI and a protease inhibitor as an initial antiretroviral treatment.

Cited by 74 publications

References 27 publications

Metabolic effects associated to the highly active antiretroviral therapy (HAART) in AIDS patients

Metabolic effects associated to the highly active antiretroviral therapy (HAART) in AIDS patients

Metabolic Syndrome Among HIV-Infected Patients

Population pharmacokinetics of indinavir alone and in combination with ritonavir in HIV‐1‐infected patients

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