Tenofovir-associated acute and chronic kidney disease: A case of multiple drug interactions
ABSTRACT Tenofovir therapy in patients with human immunodeficiency virus (HIV) infection has been associated with acute renal failure (ARF) and Fanconi syndrome. In the past 2 years, we diagnosed tenofovir-associated ARF in 5 HIV-infected patients who were receiving tenofovir therapy and who had classic findings of acute tubular necrosis, and we compared findings for our patients with data on 22 patients described in the literature. The mean serum creatinine level increased from 0.9 to 3.9 mg/dL, and it decreased to 1.2 mg/dL during recovery. ARF resolved in 22 of 27 patients after discontinuation of tenofovir therapy. The most common drugs given with tenofovir were ritonavir or lopinavir-ritonavir (21 of 27 patients), atazanavir (5 of 27 patients), and didanosine (9 of 27 patients). Tenofovir-associated ARF manifests as acute tubular necrosis that may not resolve with tenofovir withdrawal. Tenofovir is associated with multiple drug interactions, leading to an increased risk of ARF. Frequent monitoring of renal function is warranted for any patient receiving these combinations.
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ABSTRACT: The availability of highly active antiretroviral therapy has markedly improved the survival rate and quality of life in patients infected with HIV. At present, however, there is still no cure for HIV and those undergoing treatment have to do so for life. The use of antiretroviral drugs has been associated with several toxicities that limit their success. Some acute and chronic toxicities associated with these drugs include hypersensitivity reactions, neurotoxicity, nephropathy, liver damage, and the appearance of body fat redistribution syndrome and the different metabolic alterations that accompany it. Some of these toxicities are family- or even drug-specific. Since not all patients that take a particular antiretroviral medication develop the adverse effect that has been attributed to that drug, it has therefore been postulated that there must be a genetically conditioned individual predisposition to developing the adverse effect. Pharmacogenetics is the science that studies interindividual variations in the response to and toxicity of pharmaceuticals due to variations in the genetic composition of individuals - in other words, how a person's genetic make-up influences the favorable or adverse effects of a certain treatment. Sufficient advances have been made in this discipline to allow this fertile field of research to move out of the basic science laboratory and into clinical applications. The present article reviews the investigations that have been published regarding the association between genetic determinants of persons infected with HIV and clinical toxicity resulting from different antiretroviral drugs. Special emphasis is devoted to the studies that have resulted in clinical applications such as that of the pre-screening of HLA B*5701 for avoiding abacavir-related hypersensitivity syndrome.AIDS reviews 12(1):15-30. · 4.02 Impact Factor
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ABSTRACT: To determine the frequency and causes for discontinuing treatment with tenofovir and analyse possible predictive factors for changing this therapy in pretreated HIV patients. A multi-centre, observational and retrospective study of all HIV patients undergoing treatment with tenofovir between July 2002 and December 2005. Data were obtained from databases for outpatients attending the three pharmacy departments participating in the study, and by reviewing clinical histories. The main sociodemographic, clinical and analytical variables at the start of treatment with tenofovir were collected. The causes for discontinuing treatment were classified as follows: adverse effects, virological failure, death and "other causes". A survival analysis was performed using the Kaplan-Meier method to analyse the possible predictive factors for discontinuing treatment. A total of 733 patients were included in the study and the median treatment period was 34.7 months. A total of 23.8% of patients discontinued treatment for the following reasons: adverse effects (43.2%), death (17.7%), virological failure (14.8%) and "other causes" (24.4%). There were 99 cases of lost to follow-up. In the survival analysis an association was found between normal serum creatinine values (p = 0.0042) at the start of treatment and the statistically significant probability of discontinuing treatment. Almost a quarter of the patients discontinued treatment with tenofovir during the study. The main cause for this was adverse effects. No association was found between any abnormal basal analytical parameter and a greater probability of discontinuing treatment.Farmacia Hospitalaria 31(4):200-5.
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ABSTRACT: Although it has not caused overt renal damage in clinical trials, tenofovir disoproxil fumarate (TDF) has been associated with renal dysfunction in isolated cases. The objective of this study was to assess the TDF concentration with use of the glomerular filtration rate (GFR) and blood urea nitrogen (BUN) level. Serum creatinine (used to calculate GFR), BUN, and plasma TDF trough values were measured in 51 patient volunteers at pretreatment and post-treatment time points. The post-treatment GFR (post_GFR) and the difference between the pretreatment and post-treatment BUN levels (dif_BUN) were strongly related to TDF concentration. A piecewise multiple regression technique was applied to the nonlinear TDF distribution, revealing a significant association of the post_GFR and dif_BUN values with TDF concentration (P=0.002 and P= 0.003, respectively). Post_GFR values below 125 mL/min/1.73 m(2) and/or dif_BUN values below -3 mg/dL are predicted to cause a marked increase in the TDF concentration. The relationship between TDF and BUN is a new finding. Knowledge of the pretreatment and post-treatment serum creatinine and BUN levels is important for the safe clinical administration of TDF.American Journal of Therapeutics 01/2007; 14(6):514-8. DOI:10.1097/MJT.0b013e3180ed7346 · 1.13 Impact Factor