Long-term exposure to tenofovir continuously decrease renal function in HIV-1-infected patients with low body weight

Nishijima, Takeshi; Kawasaki, Yohei; Tanaka, Noriko; Mizushima, Daisuke; Aoki, Takeshi; Watanabe, Kôji; Kinai, Ei; Honda, Hirokazu; Yazaki, Hirohisa; Tanuma, Junko; Tsukada, Kunihisa; Teruya, Katsuji; Kikuchi, Yoshimi; Gatanaga, Hiroyuki; Oka, Shinichi

doi:10.1097/qad.0000000000000347

Cited by 68 publications

(80 citation statements)

References 33 publications

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“…PIs (such as those receiving pre-exposure prophylaxis) or with other risk factors support the role of genetic analysis for patients' selection. [31][32][33] Conversely in vitro studies suggested that TFV is not a substrate of MRP-2 and indirect mechanism was proposed for explaining the observed association with ABCC2 polymorphisms. 16 Some limitations of this study should, however, be considered: the cross-sectional design, the selection bias (only TFV-tolerant patients were included), the absence of in vitro studies including CNT2, the unavailability of proximal tubulopathy markers (ongoing) and wide 95% confidence intervals.…”

Section: Discussionmentioning

confidence: 93%

Clinical pharmacology of tenofovir clearance: a pharmacokinetic/pharmacogenetic study on plasma and urines

et al. 2015

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The HIV virus and hepatitis B virus nucleotide reverse transcriptase inhibitor tenofovir has been associated with proximal tubular toxicity; the latter was found to be predicted by plasma concentrations and with single-nucleotide polymorphisms in transporters-encoding genes. A cross-sectional analysis in adult HIV-positive patients with estimated creatinine clearance >60 ml min was performed. Twelve-hour plasma and urinary tenofovir concentrations and single-nucleotide polymorphisms in several transporter-encoding genes were analysed. In 289 patients 12-h tenofovir plasma, urinary and urinary to plasma ratios were 69 ng ml (interquartile range 51.5-95), 24.3 mg ml (14.3-37.7) and 384 (209-560). At multivariate analysis estimated creatinine clearance, protease inhibitors co-administration and SLC28A2 CT/TT genotypes were independently associated with plasma tenofovir exposure; ABCC10 GA/AA genotypes and protease inhibitor co-administration were independently associated with the urinary to plasma tenofovir ratio. Tenofovir clearance was associated with genetic polymorphisms in host genes and with co-administered drugs: if confirmed by ongoing studies these data may inform treatment tailoring and/or dose reductions.

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Section: Discussionmentioning

confidence: 93%

Clinical pharmacology of tenofovir clearance: a pharmacokinetic/pharmacogenetic study on plasma and urines

et al. 2015

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“…While most previously published works with shorter follow-up periods have found little variation of the eGFR related to TDF use [6], some observational studies with longer follow-up periods have found CRDRF related with TDF use [13][14][15][16][17]. It is worth mentioning some considerations about these studies.…”

Section: Discussionmentioning

confidence: 90%

“…It is worth mentioning some considerations about these studies. Some of them have been conducted in specific populations such as African population [16], among patients with low body weight [15], or treatment-naïve patients [17], and others have used the Cockcroft-Gault equation to estimate the creatinine clearance [13], which can result in an overestimate of the creatinine clearance. These situations might explain why our study shows a higher incidence of chronic kidney disease related to TDF use in the long term.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, large clinical trials with long follow-up periods of more than 144 weeks in naïve patients have shown a renal safety profile of ART containing TDF, either similar to other ART without it, or with small significant declines in the estimated glomerular filtration rate (eGFR) of clinical implications difficult to ascertain [7][8][9]. Observational studies with longer follow-up periods suggest a more deleterious effect on the renal function, and point that TDF is associated with a higher incidence of chronic kidney disease [10][11][12][13][14][15][16][17]. Overall, these results have shown either a modest or absent decline in renal function associated with TDF use after short follow-up periods of months or very few years, while studies with longer follow-up periods suggest a more relevant decrease in renal function [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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Long-term comparative and prospective cohort study of renal function in patients with HIV infection treated with tenofovir disoproxil fumarate

Calle¹,

Pulido²,

Sánchez-Conde³

et al. 2017

HIV & AIDS Review

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“…We present a simple application of the regression tree on interval-valued symbolic variables in reference to the study of HIV-1-infected patients (Nishijima et al (2014)). These data were collected to study the effect of an active drug use on renal function.…”

Section: Examplementioning

confidence: 99%

<b>CONSTRUCTION OF REGRESSION TREES ON INTERVAL-VALUED SYMBOLIC VARIABLES </b>

Shimokawa

Kawasaki²,

Miyaoka³

2014

Journal of the Japanese Society of Computational Statistics

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Analysis based on interval-valued symbolic variables, which are given as p-dimensional hyperrectangles in ℜ p , is considered appropriate in some scenarios. However, the methods analyzing these variables are not as well studied as those for classical variables, which are given as single points in ℜ p . The regression tree, which is constructed using the CART algorithm, is one such example, and we consider it in this paper. To construct a regression tree based on interval-valued symbolic variables, several models are considered. Our proposed model is different from the other models, because, in this model, a concept can be included in several terminal nodes in a tree. If we want to construct a regression tree using the proposed model, several problems such as the representation method of predictive models in each node and searching an optimal splitting point in interval values, should be addressed. We address these problems and present an application of this model in reference to the study of HIV-1-infected patients' data.

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Long-term exposure to tenofovir continuously decrease renal function in HIV-1-infected patients with low body weight

Abstract: In this cohort of patients with low body weight, TDF exposure increased the risk of renal dysfunction. Furthermore, the loss in eGFR relative to the control increased continuously up to 5 years.

Cited by 68 publications

References 33 publications

Clinical pharmacology of tenofovir clearance: a pharmacokinetic/pharmacogenetic study on plasma and urines

Clinical pharmacology of tenofovir clearance: a pharmacokinetic/pharmacogenetic study on plasma and urines

Long-term comparative and prospective cohort study of renal function in patients with HIV infection treated with tenofovir disoproxil fumarate

<b>CONSTRUCTION OF REGRESSION TREES ON INTERVAL-VALUED SYMBOLIC VARIABLES </b>

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