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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    • "Most HIV-infected patients have an abnormal muscle mass compared to that of a healthy subject; thus, more caution is required for interpretation[24]. Other previous reports investigating renal function decline prospectively had used an estimated glomerular filtration rate (eGFR)[6,7,9,14,15,17,20,25], albuminuria[6], proteinuria[24], urine protein/creatinine ratio[8], and the rate of creatinine clearance (CrCl)[24]as the indicator of decrement of renal function. However, because of retrospective nature of our study, we could not evaluate these markers that had been known as more predictive and accurate indicator. "
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    ABSTRACT: Background: The combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) has been the first choice nucleoside reverse transcriptase inhibitor (NRTI) according to many reliable antiretroviral treatment (ART) guidelines because of its high efficacy. However, TDF-related renal toxicity reported in Western countries is a challenging issue regarding clinical use. We conducted this study to evaluate the incidence and characteristics of an acute increase in serum creatinine (Cr) level > 1.5 mg/dL among TDF/FTC-based highly active antiretroviral treatment (HAART)-treated patients. Materials and methods: We retrospectively reviewed the medical records of 205 HIV-infected patients treated with TDF/FTC-containing regimens between 1 February 2010 and 30 April 2014. Three groups of TDF/FTC + ritonavir-boosted protease inhibitor (PI/r), TDF/FTC + non-nucleoside reverse transcriptase inhibitor (NNRTI), and TDF/FTC + integrase strand transfer inhibitor (INSTI), and three PI/r subgroups of TDF/FTC + lopinavir (LPV)/r, TDF/FTC + atazanavir (ATV)/r, TDF/FTC + darunavir (DRV)/r were evaluated. Results: A total 136 patients (91 in the TDF/FTC + PI/r group, 20 in the TDF/FTC + NNRTI group and 25 in the TDF/FTC + INSTI group) were included in the statistical analysis. Four cases (4.9%; all in the TDF/FTC + PI/r group) among 136 patients showed an acute increase in serum Cr more than 1.5 mg/dL, so the overall incidence was 2.8 cases per 100 patient-years. One case was a patient treated with TDF/FTC + LPV/r, and the others were treated with TDF/FTC + ATV/r. No case of an acute increase in serum Cr was observed in the TDF/FTC + DRV/r group. The incidence of serum Cr increase more than 1.5 mg/dL in TDF/FTC + PI/r group was 4.0 cases per 100 patient-years. Conclusion: Although only a small number of patients were evaluated retrospectively from a single center, the TDF/FTC + PI/r regimen may have been related with relatively higher tendency of increment of serum Cr level. These findings reinforce the importance of close follow-ups of HIV-infected patients treated with the TDF/FTC + PI/r regimens.
    Full-text · Article · Dec 2015
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    • "Differences between our study and previous publications may lie in our patient selection, sample sizes, time on TDF and the prevalence of HIV-associated nephropathy. The California Collaborative Treatment Group cohort (Goicoechea et al., 2008) was smaller with 146 patients and had fewer African-Americans than our study or the Johns Hopkins database (Gallant et al., 2009). Patients from the California Collaborative Treatment Group (Goicoechea et al., 2008) also had lower median age, lower baseline CD4 counts, and more ART-naïve patients than the HIV Outpatient Study cohort (Buchacz et al., 2006) or our study. "

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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.
    Full-text · Article · Nov 2013 · PLoS ONE
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