Renal function with use of a tenofovir-containing initial antiretroviral regimen

Department of Medicine, Johns Hopkins University School of Medicine, 1830 E. Monument Street, Baltimore, MD 21205, USA.
AIDS (London, England) (Impact Factor: 5.55). 09/2009; 23(15):1971-5. DOI: 10.1097/QAD.0b013e32832c96e9
Source: PubMed


To determine whether tenofovir disoproxil fumarate (TDF) is associated with renal dysfunction when used as part of an initial antiretroviral regimen and to assess the effect of ritonavir-boosted protease inhibitor (PI/r) coadministration on renal function in TDF-treated patients.
Analysis from a prospective observational cohort.
: We compared all antiretroviral-naive patients with an estimated glomerular filtration rate (eGFR) of more than 50 ml/min per 1.73 m (modification of diet in renal disease equation) who initiated either TDF (n = 201) or any alternative nucleoside reverse transcriptase inhibitor (NRTI) (n = 231) after 1 January 2002.
Patients taking both TDF and NRTIs experienced an initial decline in eGFR during the first 180 days of therapy, but eGFR stabilized between 180 and 720 days. There was no difference between TDF and NRTI use in 25 or 50% decline in eGFR at 1 or 2 years or in change in eGFR at 6, 12, or 24 months. Those taking TDF and a PI/r had a greater median decline in eGFR than those taking TDF and a non-NRTI at 6 months (P = 0.01), with trends at 12 (P = 0.08) and 24 months (P = 0.08). There was no difference in median GFR decline between those on an NRTI and PI/r vs. an NRTI and non-NRTI.
Our data are consistent with results of clinical trials, which have shown no evidence of renal toxicity when TDF is used as part of an initial regimen. Our results support the use of TDF as a component of the initial antiretroviral regimen, and suggest that the eGFR should be monitored more closely when TDF is used with a PI/r.

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Available from: Joel E. Gallant, Dec 26, 2013
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    • "One study argued that the initial decline in eGFR following the commencement of TDF therapy stabilized later after the first 6 months [21]. However, whether or not the initial decline stabilizes later in patients with low body weight remains to be documented in a longitudinal study of our cohort. "
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    ABSTRACT: The 2010 WHO antiretroviral therapy (ART) guidelines have resulted in increased tenofovir use. Little is known about tenofovir-induced chronic kidney disease (CKD) in HIV-infected Vietnamese with mean body weight of 55 kg. We evaluated the prevalence and risk factors of CKD in this country. Cross-sectional study was performed. Clinical data on HIV-infected Vietnamese cohort were collected twice a year. To evaluate the prevalence of CKD, serum creatinine was measured in 771 patients in October 2011 and April 2012. CKD was defined as creatinine clearance less than 60 ml/min at both time points. Multivariate logistic regression was used to determine the factors associated with CKD. Tenofovir use increased in Vietnam from 11.9% in April 2011 to 40.3% in April 2012. CKD was diagnosed in 7.3%, of which 7% was considered moderate and 0.3% was severe. Multivariate analysis of October-2011 data identified age per year-increase (OR: 1.229, 95%CI, 1.170-1.291), body weight per 1 kg-decrement (1.286, 1.193-1.386), and tenofovir use (2.715, 1.028-7.168) as risk factors for CKD. Older age, low body weight and tenofovir use were independent risk factors for CKD in Vietnam. Further longitudinal study is required to evaluate the impact of TDF on renal function in Vietnam and other countries with small-body weight patients.
    PLoS ONE 11/2013; 8(11):e79885. DOI:10.1371/journal.pone.0079885 · 3.23 Impact Factor
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    • "TDF is eliminated largely by glomerular filtration, and 20%-30% by active renal proximal tubular secretion [5]. Previous case reports reported TDF-associated renal toxicity, including acute tubular necrosis [6], Fanconi syndrome [7-9], and ultimately, renal failure [10] characterized by a decline in glomerular filtration rates (GFRs) and hypophosphatemia [11,12]. Studies with primarily Caucasian patients report low rates of tenofovir-associated nephrotoxicity, and severe renal impairment is rare in clinical trials of tenofovir-containing first line antiretroviral therapy (ART) regimens [13,14]. "
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    ABSTRACT: The aim of this study was to investigate the impact of a tenofovir disoproxil fumarate (TDF) plus ritonavir-boosted protease inhibitor (PI/r) regimen on renal function in Chinese HIV-infected patients. Seventy-five HIV-1 infected patients failing first-line antiretroviral therapy (ART) comprised the TDF+PI/r group. Seventy-five HIV-1 infected patients matched for gender, age, and renal function made up the control. All subjects completed follow-up visits over 48 weeks. CD4 cell count, plasma HIV-1 viral load, and urine protein level were assessed at the trial start (baseline, week 0) and at week 48. The serum creatinine and estimated glomerular filtration rate (eGFR) were monitored at each follow-up point. Change in eGFR from baseline to week 48 was also compared. Compared to control, the TDF+PI/r group exhibited higher levels of serum creatinine (79 vs. 69.7 mumol/L, P<0.001) and a lower rate of eGFR (93.0 vs. 101.6 ml/min/1.73m2, P=0.009) at the end of week 48. Patients treated with TDF+PI/r showed greater decline in eGFR than control (-8.8 vs. 6.4ml/min/1.73m2, P<0.001). Compared to baseline renal function of the control group, the TDF+PI/r group exhibited a greater median decline in eGFR at the end of week 48 (P<0.001). We found that a TDF+PI/r based ART regimen resulted in greater renal function decline over 48 weeks. Therefore, renal function should be monitored especially when TDF is used in combination with PI/r.Trial registration: identifier: NCT00872417.
    BMC Infectious Diseases 07/2013; 13(1):301. DOI:10.1186/1471-2334-13-301 · 2.61 Impact Factor
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    • "We reported a significant variation in the eGFR after 2 years in the entire cohort (p = 0.006) with a mean net loss of 12.1 ml/min per 1.73 m2, confirming what was reported by other studies on HIV infected adults [24,25]. We didn't find any significant eGFR variation in patients taking TDF+PI or TDF, even when compared to the group that was not treated with nor TDF nor PI, or TDF respectively. "
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    ABSTRACT: Kidney disease is an important complication in HIV infected people, and this may be related to infection or antiretroviral therapy (ART). Our aim is to assess renal function in HIV infected paediatric patients, who may be particularly affected and are likely to take ART for longer than adults, and investigate the long term role of Tenofovir Disoproxil Fumarate (TDF) alone or co-administered with Ritonavir-boosted Protease Inhibitors (PI). Serum creatinine, phosphate and potassium levels, with estimated Glomerular Filtration Rate (eGFR), had been prospectively evaluated for 2 years in a cohort of HIV infected children and adolescents (age 9-18) on ART, and data analyzed according to the exposure to TDF or simultaneous TDF and PI. Forty-nine patients were studied (57% female, mean age 14). Sixty-three percent were treated with ART containing TDF (Group A), and 37% without TDF (Group B); 47% with concomitant use of TDF and PI (Group C) and 53% without this combination (Group D). The groups didn't differ for age, gender or ethnicity. The median creatinine increased in the entire cohort and in all the groups analyzed; eGFR decreased from 143.6 mL/min/1.73 m2 at baseline to 128.9 after 2 years (p = 0.006) in the entire cohort. Three patients presented a mild eGFR reduction, all were on TDF+PI. Phosphatemia decreased significantly in the entire cohort (p = 0.0003) and in TDF+PI group (p = 0.0128) after 2 years. Five patients (10%) developed hypophosphatemia (Division of Acquired Immune Deficiency AE grade 1 or 2), and four of them were on TDF+PI. Renal function decrease and hypophosphatemia occur over time in HIV infected children and adolescents on ART. The association with co-administration of TDF and PI appears weak, and further studies are warranted.
    BMC Infectious Diseases 01/2012; 12(1):18. DOI:10.1186/1471-2334-12-18 · 2.61 Impact Factor
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