Impact of Tenofovir on Renal Function in HIV-Infected, Antiretroviral-Naive Patients

Horberg, Michael A.; Tang, Beth; Towner, William; Silverberg, Michael J.; Bersoff‐Matcha, Susan; Hurley, Leo B.; Chang, Joseph Tung-Chieh; Blank, Jackie; Quesenberry, Charles P.; Klein, Daniel B.

doi:10.1097/qai.0b013e3181be6be2

Cited by 131 publications

(108 citation statements)

References 41 publications

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“…They found an identical prevalence as in our study, and any tenofovir (TDF) use, as well as any indinavir (IDV) use, was associated with a higher risk of CKD (5). A recent study investigated the effect of tenofovir on renal function in 1647 ARV-naïve HIV-infected patients (25). Again, this study focused on tenofovir exposure and concluded that tenofovir was associated with greater effect on decline in renal function.…”

Section: Discussionsupporting

confidence: 76%

“…Our study shows statistical association between ARV drugs and CKD that needs to be documented further to identify nephrotoxic mechanisms. Tenofovir and indinavir have been shown to be related to nephrotoxicity in many studies (2,5,6,10,11,25). Some factors (hepatitis B or C and diabetes) traditionally reported as related to CKD in persons with or without HIV-1 infection were not found to be independently associated with the occurrence of CKD in our analysis (5,26,27).…”

Section: Discussionmentioning

confidence: 48%

“…Many studies have investigated predictive factors of GFR changes (21)(22)(23), whereas fewer studies have been conducted on large data sets investigating factors associated with CKD (5,24,25). To our knowledge, our study is the largest cohort of HIV-infected adults investigating risk factors of CKD, especially the effect of each ARV drug.…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…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].…”

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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Changes in Glomerular Kidney Function Among HIV-1–Uninfected Men and Women Receiving Emtricitabine–Tenofovir Disoproxil Fumarate Preexposure Prophylaxis

et al. 2015

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IMPORTANCE Tenofovir disoproxil fumarate (TDF) use has been associated with declines in the estimated glomerular filtration rate (eGFR) when used as part of antiretroviral treatment by persons with human immunodeficiency virus (HIV) type 1, but limited data are available for risk when used as preexposure prophylaxis (PrEP) for HIV-1 prevention.OBJECTIVE To determine whether TDF-based PrEP causes eGFR decline in HIV-1-uninfected adults. DESIGN, SETTING, AND PARTICIPANTSA per-protocol safety analysis of changes in eGFR in the Partners PrEP Study, a randomized, placebo-controlled trial of daily oral TDF and emtricitabine (FTC)-TDF PrEP among heterosexual HIV-1-uninfected members of serodiscordant couples in Kenya and Uganda. The trial was conducted from 2008 to 2012. MAIN OUTCOMES AND MEASURESPredefined outcomes of this analysis were mean eGFR change and a 25% or greater eGFR decline from baseline. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTSOf 4640 participants in the once-daily TDF (n = 1548), FTC-TDF (n = 1545), or placebo (n = 1547) groups, 63% were men. At enrollment, median age was 35 years (range, 18-64 years), and mean eGFR was 130 mL/min/1.73 m 2 . During a median follow-up of 18 months (interquartile range 12-27 months), mean within-group eGFR change from baseline was +0.14 mL/min/1.73 m 2 for TDF, −0.22 mL/min/1.73 m 2 for FTC-TDF, and +1.37 mL/min/1.73 m 2 for placebo, translating into average declines in eGFR attributable to PrEP vs placebo of −1.23 mL/min/1.73 m 2 (95% CI, −2.06 to −0.40; P = .004) for TDF and −1.59 mL/min/1.73 m 2 (95% CI, −2.44 to −0.74; P < .001) for FTC-TDF. The difference in mean eGFR between PrEP and placebo appeared by 1 month after randomization, was stable through 12 months, and then appeared to wane thereafter. The respective proportions of persons who developed a confirmed 25% or greater eGFR decline from baseline by 12 and 24 months was 1.3% and 1.8% for TDF and 1.2% and 2.5% for FTC-TDF, and these frequencies were not statistically different from the confirmed decline in the placebo group (0.9% and 1.3% by 12 and 24 months, respectively). CONCLUSIONS AND RELEVANCEIn this large randomized, placebo-controlled trial among heterosexual persons, with median follow-up of 18 months and maximum follow-up of 36 months, daily oral TDF-based PrEP resulted in a small but nonprogressive decline in eGFR that was not accompanied by a substantial increase in the risk of clinically relevant (Ն25%) eGFR decline. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00557245

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Impact of Tenofovir on Renal Function in HIV-Infected, Antiretroviral-Naive Patients

Abstract: Tenofovir is associated with greater effect on decline in renal function and a higher risk of proximal tubular dysfunction in antiretroviral naïve patients initiating antiretroviral therapy.

Cited by 131 publications

References 41 publications

Risk Factors of Chronic Kidney Disease in HIV-infected Patients

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*

Changes in Glomerular Kidney Function Among HIV-1–Uninfected Men and Women Receiving Emtricitabine–Tenofovir Disoproxil Fumarate Preexposure Prophylaxis

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