Long-term renal safety of tenofovir disoproxil fumarate in antiretroviral-naive HIV-1-infected patients. Data from a double-blind randomized active-controlled multicentre study

Izzedine, Hassane; Hulot, Jean‐Sébastien; Vittecoq, D.; Gallant, Joel E.; Staszewski, S; Launay‐Vacher, Vincent; Cheng, Andrew; Deray, Gilbert

doi:10.1093/ndt/gfh658

Cited by 169 publications

(109 citation statements)

References 16 publications

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“…Tenofovir may have contributed to ATN in three additional patients presenting with septic shock (two patients) and in conjunction with metformin (one patient), because they all displayed proximal tubular dysfunction. Tenofovir has gained widespread use for the treatment of HIV-1 and hepatitis B infections on the basis of its efficacy and tolerability (21)(22)(23)(24). Phase III studies showed excellent renal safety, but cases of tenofovirrelated nephrotoxicity were first reported in 2002 (12,25).…”

Section: Discussionmentioning

confidence: 99%

Tubulointerstitial Nephropathies in HIV-Infected Patients over the Past 15 Years

Zaidan

Lescure

Brochériou

et al. 2013

Clinical Journal of the American Society of Nephrology

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Summary Background and objectives The therapy and outcome of HIV infection have dramatically changed over the last 15 years, resulting in a change in renal complications. This study analyzed the characteristics of HIV-infected patients and biopsy-proven tubulointerstitial nephropathies to define disease patterns and therapeutic implications. Design, setting, participants, & measurements A clinico-pathologic retrospective study of 59 consecutive renal biopsies showing predominant tubular and/or interstitial lesions in HIV-infected patients referred to the nephrology department between 1995 and 2011 was performed. HIV-associated nephropathy and vascular diseases were excluded from the study. Results Tubulointerstitial nephropathies accounted for 26.6% of 222 native renal biopsies performed in HIV-infected patients. Two pathologic groups were analyzed, tubulopathy and interstitial nephritis, which represented 49% and 51% of tubulointerstitial nephropathies, respectively. Most patients presented with AKI (76.3%) and high-grade proteinuria (57.7%). Drug-related nephrotoxicity was the leading cause (52.5%). Alternative etiologies included infections (15.2%), dysimmune disorders (8.5%), malignancies (3.4%), and chronic (10.2%) and acute (10.2%) tubulointerstitial nephropathies of undetermined origin. Tubulopathy was strongly associated with antiretroviral drug toxicity (75.9%) and mostly caused by tenofovir (55.2%), which was associated with proximal tubular dysfunction (87.5%), overt Fanconi’s syndrome (37.5%), and nephrogenic diabetes insipidus (12.5%). Interstitial nephritis was associated with a broader spectrum of pathologic lesions and etiologies. Conclusions In this series, tubulointerstitial nephropathies accounted for 26.6% of renal diseases in HIV-infected patients. Considering the therapeutic implications of diagnoses of drug toxicity, infection, and dysimmune syndromes, this study underscores the importance of monitoring renal parameters in HIV-infected patients and points to the relevance of kidney biopsy to allow an accurate diagnosis.

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Section: Discussionmentioning

confidence: 99%

Tubulointerstitial Nephropathies in HIV-Infected Patients over the Past 15 Years

Zaidan

Lescure

Brochériou

et al. 2013

Clinical Journal of the American Society of Nephrology

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“…Most previous studies of the relationship between renal function and antiretrovirals have been on the basis of small or moderate patient groups and have tended to focus exclusively on tenofovir (16,21,22,25,27,28). In EuroSIDA, 4474 patients were analyzed, and many antiretrovirals were investigated as being associated with chronic renal failure.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors of Chronic Kidney Disease in HIV-infected Patients

Flandre¹,

Puglièse²,

Cuzin³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives The main aim of this study was determining the risk factors of chronic kidney disease (CKD) in HIV-1-infected patients.Design, setting, participants, & measurements Patients were followed from seven large HIV reference centers in France that maintain prospective databases on HIV-1-infected patients. The main outcome was the time to CKD defined as two consecutive measures of estimated GFR Յ60 ml/min per 1.73 m 2 over Ն3 months. A Cox's model with delayed entry was used to search predictive factors of time to CKD.Results From 1993 to 2006, 349 out of 7378 patients were found to have CKD. Of these, 166 had hypertension, 33 had diabetes, and 26 were antiretroviral therapy-naïve. Occurrence of acute kidney injury (hazard ratio [HR] ϭ 2.40) and hypertension (HR ϭ 2.39) were strongly associated with an increased risk of CKD. Patients with a durable level of CD4 count Ͼ200 cells/mm 3 had a lower risk of CKD (HR ϭ 0.63). Recent exposure to indinavir (HR ϭ 2.03), totenofovir (HR ϭ 1.55), and abacavir (HR ϭ 1.37) were associated with an increased risk of CKD. Past exposure to tenofovir was also associated with an increased risk of CKD (HR ϭ 2.23), and a trend toward significance was observed for past exposure to indinavir (HR ϭ 1.28).Conclusions CKD was not rare in HIV-infected patients and occurs preferentially in HIV-infected patients exposed to certain ARVs, specifically abacavir, indinavir and tenofovir. This requires closer monitoring of renal function in patients exposed to one of these drugs.

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“…As a consequence of its tolerability, convenient dosing and efficacy, this nucleoside reverse transcriptase inhibitor (NRTI) has been widely used as a component of cART regimens. There are contradictory data on tenofovir-related damage: from documented damage in early reports [24][25][26][27] to a marked lack of renal toxicity in randomized placebo-controlled trials [28][29][30][31]; moreover, toxicity was found to be increased when tenofovir was given with ritonavir-boosted protease inhibitors (PI/r) compared with tenofovir given with nonnucleoside reverse transcriptase inhibitors (NNRTIs) or cART that did not include tenofovir [32]. A mechanism involving an interaction between tenofovir and PIs/r resulting in an increased risk of renal damage has been suggested [33].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of glomerular filtration rate in HIV-1-infected patients before and after combined antiretroviral therapy exposure*

et al. 2010

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The prevalence and factors associated with an increased risk of renal dysfunction in HIV-infected patients receiving or not receiving antiretroviral therapy (ART) have been poorly evaluated in observational settings. MethodsPatients in the ICONA Foundation cohort with at least two creatinine values available while still ART-naïve were enrolled in the study. A logistic regression analysis was performed to identify predictors of an estimated glomerular filtration rate (eGFR)o90 mL/min/1.73 m 2 at baseline. The incidence and predictors of a 420% reduction in eGFR from pre-combination ART (cART) levels (or a decrease from ! 90 to o90 mL/min/1.73 m 2 ) were evaluated by Poisson regression. ResultsA total of 1505 patients were included in the study; 363 (24%) had eGFRo90 mL/min/1.73 m 2 at baseline. Older patients [odds ratio (OR) 1.58 per 10 years older; Po0.00001], female patients (OR 2.41 vs. male patients; Po0.00001), those who had diabetes and/or hypertension (OR 2.36 vs. neither; Po0.03) and patients with higher baseline CD4 count (OR 1.06 per 100 cells/mL higher; Po0.03) showed a greater risk of eGFRo90 mL/min/1.73 m 2 . Ninety-six patients experienced an eGFR decrease of 420% from pre-cART levels (6.8 per 100 person-years). Older age [relative risk (RR) 1.41 per 10 years older; P 5 0.005], female gender (RR 2.25 vs. male; P 5 0.003) and current exposure to didanosine (ddI), tenofovir and protease inhibitors were the major determinants. ConclusionsWe observed a relatively high rate of mild renal dysfunction in the absence of ART. In addition to traditional risk factors such as older age and diabetes/hypertension, female gender and current use of ddI, tenofovir and protease inhibitors were associated with a greater risk of decreased renal function as measured by eGFR.Keywords: antiretroviral exposure, estimated glomerular filtration rate (eGFR), renal impairment [7][8][9][10][11], there are a number of other factors potentially influencing the onset of renal disorders through different mechanisms, whose prevalence may be different in an HIV-positive population compared with the general population. Indeed, patients' longer survival following the introduction of cART may be considered as an additional risk for renal dysfunction, as long-term toxic events associated with the prolonged used of ART have been observed (e.g. metabolic alterations, diabetes, hypertension and cardiovascular events) [12][13][14]. It has been hypothesized that antiretroviral medications may have a direct effect in increasing the risk of renal dysfunction, and a variety of cART-related effects, including proteinuria, renal tubular damage, interstitial nephritis and overall declines in glomerular filtration rates, have been noted [15][16][17][18][19][20][21][22][23].The potential role of tenofovir in renal toxicity is a current clinical research question. As a consequence of its tolerability, convenient dosing and efficacy, this nucleoside reverse transcriptase inhibitor (NRTI) has been widely used as a component of cART regimens. There are...

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Long-term renal safety of tenofovir disoproxil fumarate in antiretroviral-naive HIV-1-infected patients. Data from a double-blind randomized active-controlled multicentre study

Abstract: Through 144 weeks, TDF and stavudine, each administered in combination with efavirenz and lamivudine, had similar renal safety profiles in treatment-naive HIV-infected patients with normal renal function at baseline.

Cited by 169 publications

References 16 publications

Tubulointerstitial Nephropathies in HIV-Infected Patients over the Past 15 Years

Tubulointerstitial Nephropathies in HIV-Infected Patients over the Past 15 Years

Risk Factors of Chronic Kidney Disease in HIV-infected Patients

Evaluation of glomerular filtration rate in HIV-1-infected patients before and after combined antiretroviral therapy exposure*

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