ArticlePloS one2015
Metabolic and kidney disorders correlate with high atazanavir concentrations in HIV-infected patients: is it time to revise atazanavir dosages?
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 27 citations in OpenAlex.
- Obesity Modifies the Relationship Between Raltegravir and Dolutegravir Hair Concentrations and Body Weight Gain in Women Living with HIV.AIDS research and human retroviruses · 2023Article
- Ureterolithiasis in Human Immunodeficiency Virus (HIV) Patients Treated with Single-Use Ureteroscope: A Case Report.The American journal of case reports · 2022Article
- Long-term kidney function, proteinuria, and associated risks among HIV-infected and uninfected men.AIDS (London, England) · 2018Article
- Antiretroviral Drug Metabolism in Humanized PXR-CAR-CYP3A-NOG Mice.The Journal of pharmacology and experimental therapeutics · 2018Article
- Development and validation of an assay to analyze atazanavir in human hair via liquid chromatography/tandem mass spectrometry.Rapid communications in mass spectrometry : RCM · 2018Article
- Kidney Disease in HIV: Moving beyond HIV-Associated Nephropathy.Journal of the American Society of Nephrology : JASN · 2017Review
- Novel Antiretroviral Drugs in Patients with Renal Impairment: Clinical and Pharmacokinetic Considerations.European journal of drug metabolism and pharmacokinetics · 2017Review
- Ureteral Obstruction Due to Radiolucent Atazanavir Ureteral Stones.Journal of endourology case reports · 2017Article
- HIV and kidney diseases: 35 years of history and consequences.Clinical kidney journal · 2016Review
- Effect of hepatitis B and C clearance on atazanavir exposure.European journal of clinical pharmacology · 2015Article
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionRitonavir-boosted atazanavir (ATV/r) is a relatively well tolerated antiretroviral drug. However, side effects including hyperbilirubinemia, dyslipidemia, nephrolithiasis and cholelithiasis have been reported in the medium and long term. Unboosted ATV may be selected for some patients because it has fewer gastrointestinal adverse effects, less hyperbilirubinemia and less impact on lipid profiles.
methodsWe investigated the distribution of ATV plasma trough concentrations according to drug dosage and the potential relationship between ATV plasma trough concentrations and drug-related adverse events in a consecutive series of 240 HIV-infected patients treated with ATV/r 300/100 mg (68%) or ATV 400 mg (32%).
results43.9% of patients treated with ATV/r 300/100 mg had ATV concentrations exceeding the upper therapeutic threshold. A significant and direct association has been observed between the severity of hyperbilirubinemia and ATV plasma trough concentrations (ATV concentrations: 271 [77-555], 548 [206-902], 793 [440-1164], 768 [494-1527] and 1491 [1122-1798] ng/mL in patients with grade 0, 1, 2, 3 and 4 hyperbilirubinemia, respectively). In an exploratory analysis we found that patients with dyslipidemia or nephrolitiasis had ATV concentrations significantly higher (582 [266-1148], and 1098 [631-1238] ng/mL, respectively) (p<0.001), as compared with patients with no ATV-related complications (218 [77-541] ng/mL).
conclusionsA significant proportion of patients treated with the conventional dosage of ATV (300/100) had plasma concentrations exceeding the upper therapeutic threshold. These patients that are at high risk to experience ATV-related complications may benefit from TDM-driven adjustments in ATV dosage with potential advantages in terms of costs and toxicity.
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