Serum creatinine changes in HIV-seropositive patients receiving tenofovir

Sahly, Hana M. El; Teeter, Larry D.; Zerai, Teddy; Andrade, Roberto; Muñoz, Carmen García; Nnabuife, Calista; Hunter, Rodney J.

doi:10.1097/01.aids.0000216386.60481.47

Cited by 11 publications

(9 citation statements)

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“…a few months), of other ARV drugs (IDV and tenofovir) with renal function impairment. In accordance with other reports [9,14,[24][25][26][27][28], our results indicate an association of mild RI with the use of tenofovir. In an additional analysis where current use of tenofovir was added to the model, we found a statistical association between this latter variable but not with cumulative exposure to the drug.…”

Section: Discussionsupporting

confidence: 93%

Prevalence and factors associated with renal impairment in HIV‐infected patients, ANRS C03 Aquitaine Cohort, France

et al. 2010

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ObjectivesThe aims of the present study were to estimate the prevalence of renal impairment (RI) among HIV-infected adult patients and to investigate the associated factors. MethodsA cross-sectional survey was conducted in a French hospital-based cohort. Clearance of creatinine (CC) was calculated using the Cockcroft-Gault formula. Four stages of RI were defined: mild (60-90 mL/min), moderate (30-60), severe (15-30) and end stage (o15). Logistic regression models were used to investigate factors associated with RI. ResultsThe male/female ratio of the 2588 patients enrolled was 3:1 and the median age was 42 years. At the time of assessment of CC, the median CD4 count was 430 cells/mL and HIV plasma viral load (VL) waso50 copies/mL in 60%. The overall prevalence of RI was 39.0%: 34.2% mild, 4.4% moderate, 0.3% severe and 0.2% end-stage. Mild RI was associated with female gender [odds ratio (OR) 5 3.3: 95% CI 2.6-4.3)], age 450 years (OR 5 9.8: 7.4-13.0) and 40-50 years (OR 5 1.9: 1.5-2.4), body mass index (BMI) o22 kg/m 2 (OR 5 3.3: 2.7-4.3) and tenofovir exposure (OR 5 1.4: 1.0-1.9 for o1 year and OR 5 1.5: 1.2-2.0 for 41 year). Advanced RI (CC o60 mL/min) was associated with age 450 years (OR 5 5.6: 2.9-10.9) and 40-50 years (OR 5 2.2: 1.1-1.4), BMI o22 kg/m 2 (OR 5 1.5: 1.0-2.4), hypertension (OR 5 2.5: 1.4-2.5) and indinavir (IDV) exposure 41 year (OR 5 2.3: 1.5-3.6). ConclusionThis survey confirms the high prevalence of RI in HIV-infected patients and indicates the importance of the investigation of renal function especially in women, older patients, those with a low BMI or treated with tenofovir or IDV.Keywords: HIV infection, kidney, renal impairment Accepted 11 August 2009Introduction Nowadays kidney morbidity has become common among HIV-infected patients in industrialized countries [1]. Specific renal damage characterizes the HIV-associated nephropathy (HIVAN) [2,3] and several risk factors have been hypothesized and investigated individually including black ethnicity, male gender, a history of injection drug use, hepatitis C virus (HCV) co-infection, low CD4 cell count and a concurrent AIDS-defining condition. HIVAN may result in renal function impairment [4,5], although the use of antiretroviral therapy (ART) has recently contributed to lower its prevalence [6,7]. Nevertheless, the overall survival improvement of HIV-infected patients receiving ART leads to the accumulation of factors that are harmful for renal function: ageing, comorbidities such as high blood pressure, diabetes, hyperlipidemia and adverse DOI: 10.1111/j.1468-1293.2009.00780.x HIV Medicine (2010 r 2009 British HIV Association 308 effects of ARV drugs such as indinavir (IDV) and tenofovir [8]. These factors are thus likely to again increase the frequency of acute or chronic renal impairment (RI) [9]. Studies on the frequency of RI in HIV-infected patients have often been conducted in selected groups of HIVinfected patients and additional studies are needed to allow a proper estimation of its prevalence and comprehensive investigation ...

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Section: Discussionsupporting

confidence: 93%

Prevalence and factors associated with renal impairment in HIV‐infected patients, ANRS C03 Aquitaine Cohort, France

et al. 2010

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“…In addition, the low baseline CrCl is probably indicative of underlying renal disease even before exposure to TDF. Others have also shown that baseline serum creatinine, age, CD4 count, low hemoglobin, BMI, and CrCl are associated with decline in renal function among TDF-treated patients [27–31]. …”

Section: Discussionmentioning

confidence: 99%

“…Hence, the frequency of laboratory monitoring of ART patients remains a relevant topic. The DART trial suggested that toxicity monitoring did not improve overall outcomes among individuals receiving either AZT/3TC/TDF or AZT/3TC/NVP [32] and renal events have been low in other clinical trials using TDF in resource limited settings [31]. Based on these findings, many countries using TDF-based therapy for first line therapy are not conducting routine renal toxicity monitoring.…”

Section: Discussionmentioning

confidence: 99%

Renal events among women treated with tenofovir/emtricitabine in combination with either lopinavir/ritonavir or nevirapine

Mwafongo¹,

Nkanaunena

Zheng

et al. 2014

Aids

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Objectives Tenofovir disoproxil fumarate (TDF) has been associated with renal insufficiency. Co-administration with boosted protease inhibitors (PIs), which increases its exposure, may further increase the risk of renal insufficiency. Methods We compared the incidence of renal events among women taking TDF co-administered with lopinavir/ritonavir (LPV/r) versus those co-administering TDF with nevirapine (NVP). Renal events were defined as a confirmed drop in creatinine clearance associated with a serum creatinine grade 2 or higher, or that leading to treatment modification. Results Overall, 741 HIV-infected women were enrolled into the study. Of these, 24 (3.2%) had reportable renal events (18 in LPV/r arm, 6 in NVP arm). In multivariate analysis, renal events were significantly associated with the LPV/r arm (odds ratio [OR]=3.12, 95% confidence interval [CI] 1.21, 8.05]; p=0.019), baseline HIV-1 RNA (OR=2.65, 95% CI: 1.23, 5.69 per 1 log10 copies/mL higher; p=0.013) and baseline creatinine clearance (OR=0.83, 95% CI 0.70–0.98 per 10 mL/min higher; p=0.030). In multivariate analysis evaluating renal events requiring treatment modification, only baseline HIV-1 RNA and creatinine clearance were significantly associated (OR=4.41, 95% CI 1.65, 11.78 per 1 log10 copies/mL higher; p= 0.003 and OR=0.80, 95% CI 0.64, 0.99 per 10 mL/min higher; p= 0.040, respectively). Conclusion The rates of renal events were relatively low in the two treatment arms. However, patients taking TDF co-administered with LPV/r had significantly more renal events compared to those co-administered with NVP. Furthermore, higher baseline HIV RNA and lower creatinine clearance were associated with the development of renal insufficiency requiring treatment modification.

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“…Renal toxicity is usually manifested as renal insufficiency and proximal renal tubular dysfunction (PRTD). During clinical trials of TDF, the frequency of clinically significant renal changes was very low among populations with normal renal values at baseline (and not different from the frequencies seen with other highly active antiretroviral therapy regimens [24,27,37,49,53,69]); furthermore, renal toxicity has been observed infrequently through continued clinical monitoring as described in case reports and cohort study reports (8,21,22,27,35,37,44,47,48,53,70,71). Some reports on TDF-treated populations describe small reductions in creatinine clearance that remained within the normal range and were thus of uncertain clinical significance (22,24,25,37,40,70).…”

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confidence: 99%

Chronic Administration of Tenofovir to Rhesus Macaques from Infancy through Adulthood and Pregnancy: Summary of Pharmacokinetics and Biological and Virological Effects

Rompay

Durand-Gasselin

Brignolo

et al. 2008

Antimicrob Agents Chemother

112

102

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The reverse transcriptase (RT) inhibitor tenofovir (TFV) is highly effective in the simian immunodeficiency virus (SIV) macaque model of human immunodeficiency virus infection. The current report describes extended safety and efficacy data on 32 animals that received prolonged (>1-to 13-year) daily subcutaneous TFV regimens. The likelihood of renal toxicity (proximal renal tubular dysfunction [PRTD]) correlated with plasma drug concentrations, which depended on the dosage regimen and age-related changes in drug clearance. Below a threshold area under the concentration-time curve for TFV in plasma of ϳ10 g ⅐ h/ml, an exposure severalfold higher than that observed in humans treated orally with 300 mg TFV disoproxil fumarate (TDF), prolonged TFV administration was not associated with PRTD based on urinalysis, serum chemistry analyses, bone mineral density, and clinical observations. At low-dose maintenance regimens, plasma TFV concentrations and intracellular TFV diphosphate concentrations were similar to or slightly higher than those observed in TDF-treated humans. No new toxicities were identified. The available evidence does not suggest teratogenic effects of prolonged low-dose TFV treatment; by the age of 10 years, one macaque, on TFV treatment since birth, had produced three offspring that were healthy by all criteria up to the age of 5 years. Despite the presence of viral variants with a lysine-to-arginine substitution at codon 65 (K65R) of RT in all 28 SIV-infected animals, 6 animals suppressed viremia to undetectable levels for as long as 12 years of TFV monotherapy. In conclusion, these findings illustrate the safety and sustained benefits of prolonged TFV-containing regimens throughout development from infancy to adulthood, including pregnancy.Because at present it is not possible to cure human immunodeficiency virus (HIV) infection, prolonged treatment with combinations of anti-HIV drugs is required in order to prevent disease progression. The feasibility of giving HIV-infected persons a normal life span through chronic treatment will be determined by a number of factors, including compliance and cost, but especially the long-term safety and efficacy of the drugs.The nucleotide reverse transcriptase (RT) inhibitor tenofovir {TFV; 9-[2-(phosphonomethoxy)propyl]adenine}, in the form of its orally bioavailable prodrug TFV disoproxil fumarate (TDF), has become one of the most commonly used anti-HIV drugs due to its favorable efficacy and safety profile, based on data collected over more than 7 years for HIV-infected adults (12,24,35,37,47,49).The acyclic nucleoside phosphonates cidofovir, adefovir, and TFV are renally excreted by a combination of glomerular filtration and active tubular secretion (14,15,18,38). The effective uptake of acyclic nucleoside phosphonates by organic anion transporters in proximal tubules leads to accumulation in tubular cells and dose-limiting toxicity in animals (5, 63). Renal toxicity is usually manifested as renal insufficiency and proximal renal tubular dysfunction (PRTD). Dur...

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Serum creatinine changes in HIV-seropositive patients receiving tenofovir

Cited by 11 publications

References 4 publications

Prevalence and factors associated with renal impairment in HIV‐infected patients, ANRS C03 Aquitaine Cohort, France

Prevalence and factors associated with renal impairment in HIV‐infected patients, ANRS C03 Aquitaine Cohort, France

Renal events among women treated with tenofovir/emtricitabine in combination with either lopinavir/ritonavir or nevirapine

Chronic Administration of Tenofovir to Rhesus Macaques from Infancy through Adulthood and Pregnancy: Summary of Pharmacokinetics and Biological and Virological Effects

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