Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients

Mocroft, Amanda; Kirk, Ole; Reiss, Peter; Wit, Stéphane De; Sedláček, Dalibor; Beniowski, Marek; Gatell, José M.; Phillips, Andrew; Ledergerber, Bruno; Lundgren, Jens D.

doi:10.1097/qad.0b013e328339fe53

Cited by 369 publications

(397 citation statements)

References 59 publications

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“…A previous study suggested an association between the use of ATV, TDF, or indinavir and creatinine clearance, as indicated by a persistent reduction in glomerular filtration rate over time. 56 The biological explanations for these findings are unclear, but may include glomerular dysfunction, high renal excretion rates, and/or crystalluria. 56 Though the current study observed modest changes over 48 weeks, the ARTEMIS study did not show any changes in creatinine clearance over 96 weeks, 39 suggesting that longterm use of DRV/r has little effect on creatinine clearance.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

Aberg

Tebas

Overton

et al. 2012

AIDS Research and Human Retroviruses

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We assessed metabolic changes for darunavir/ritonavir (DRV/r) once daily (qd) versus atazanavir/ritonavir (ATV/r) qd with fixed-dose tenofovir/emtricitabine. This was a phase 4, multicenter, open-label, randomized exploratory study. Treatment-naive, HIV-1-infected adults received DRV/r 800/100 mg qd or ATV/r 300/ 100 mg qd, both with emtricitabine/tenofovir 200/300 mg qd. Primary end point: change in triglyceride levels from baseline to week 12. Secondary end points: week 12 and week 48 changes in lipid parameters, insulin sensitivity, inflammatory/coagulation/bacterial translocation biomarkers, viral load, CD4 + cell count, and week 48 changes in adipose tissue distribution and subjects' perceptions of body changes. In the DRV/r arm, 32/34 and 29/34 subjects completed weeks 12 and 48, respectively; in the ATV/r arm, 30/31 and 25/31 subjects completed weeks 12 and 48, respectively. Small changes in lipid parameters from baseline to weeks 12 and 48 were observed in both arms. Differences were noted between arms in mean changes in total cholesterol (DRV/r, 20.3 mg/dl; ATV/r, 4.6 mg/dl) and apolipoprotein A1 (DRV/r, 10.7 mg/dl; ATV/r, -0.7 mg/dl) at week 12. At week 48, no clinically relevant differences between arms were noted for changes in any lipid parameter, fasting glucose, or insulin sensitivity. Biomarkers generally decreased and efficacy parameters improved in both arms over 48 weeks. Changes in adipose tissue were small and comparable between arms. Subjects' perceptions of body changes generally improved in both study arms. This first pilot comparison in HIV-1-infected subjects suggests that DRV/r has a metabolic profile similar to ATV/r over 48 weeks of treatment. Further randomized studies are warranted.

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Section: Discussionmentioning

confidence: 99%

Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

Aberg

Tebas

Overton

et al. 2012

AIDS Research and Human Retroviruses

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“…Results from European cohorts show a prevalence of kidney disease (eGFR < 60 mL/ min/1.73 m 2 ) to be 2-5%. [21][22][23] The relatively low median age (48 years) of our patients likely explains this finding. However, the high prevalence of patients with signs of renal damage, most of whom had an eGFR > 60 mL/min/1.73 m 2 is similar to other results recently reported elsewhere, 21 and, contrary, is lower than others regarding the proportion of proteinuria detected.…”

Section: Discussionmentioning

confidence: 45%

“…30,31 Our data showed that the use of tenofovir combined with a protease inhibitor increased the risk of kidney disease (abnormal eGFR and abnormal UPC or UAC ratios), as previously described in large cohorts. 15,22,32 Higher tenofovir plasma concentration was associated with alterations in renal markers (both glomerular and tubular), 33,34 and the highest plasma exposure was associated with the concomitant use of protease inhibitors. 35 However, whether co-administered or not with protease inhibitors, tenofovir was not associated with proteinuria > 300 mg/g in our cohort.…”

Section: Discussionmentioning

confidence: 99%

High Prevalence of Signs of Renal Damage Despite Normal Renal Function in a Cohort of HIV-Infected Patients: Evaluation of Associated Factors

Bonjoch

Juega

Puig

et al. 2014

AIDS Patient Care and STDs

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Renal disorders are an emerging problem in HIV-infected patients. We performed a cross-sectional study of the first 1000 HIV-infected patients attended at our HIV unit who agreed to participate. We determined the frequency of renal alterations and its related risk factors. Summary statistics and logistic regression were applied. The study sample comprised 970 patients with complete data. Most were white (94%) and men (76%). Median (IQR) age was 48 (42-53) years. Hypertension was diagnosed in 19%, dyslipidemia in 27%, and diabetes mellitus in 3%. According to the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation, 29 patients (3%) had an eGFR < 60 ml/min/1.73 m 2 ; 18 of them (62%) presented altered albumin/creatinine and protein/creatinine (UPC or UAC) ratios. Of the patients with eGFR > 60 mL/min, it was present in 293 (30%), 38 of whom (7.1%) had UPC > 300 mg/g. Increased risk of renal abnormalities was correlated with hypertension (OR, 1.821 [95%CI, 1.292;2.564]; p = 0.001), age (OR, 1.015 [95%CI, 1.001;1.030], per one year; p = 0.040), and use of tenofovir disoproxil fumarate (TDF) plus protease inhibitor (PI), (OR, 1.401 [95%CI, 1.078;1.821]; p = 0.012). Current CD4 cell count was a protective factor (OR, 0.9995 [95%CI, 0.9991;0.9999], per one cell; p = 0.035). A considerable proportion of patients presented altered UPC or UAC ratios, despite having an eGFR > 60 mL/min. CD4 cell count was a protective factor; age, hypertension, and use of TDF plus PIs were risk factors for renal abnormalities. Based on our results, screen of renal abnormalities should be considered in all HIV-infected patients to detect these alterations early.

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“…Although this difference was not significant, the results are not unexpected due to the negative impact of protease inhibitors on tenofovir-related kidney or bone toxicity. 23,24 The small sample size of the abacavir-lamivudine group is a limitation of the study. However, the only existing data on the combination abacavir/lamivudine plus raltegravir included 35 antiretroviral-naive patients, and thus the number of patients with this combination of interest was almost double in our study.…”

Section: Discussionmentioning

confidence: 99%

Abacavir/Lamivudine Versus Tenofovir/Emtricitabine in Virologically Suppressed Patients Switching from Ritonavir-Boosted Protease Inhibitors to Raltegravir

Martínez

D'albuquerque²,

Pérez³

et al. 2013

AIDS Research and Human Retroviruses

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There are few clinical data on the combination abacavir/lamivudine plus raltegravir. We compared the outcomes of patients from the SPIRAL trial receiving either abacavir/lamivudine or tenofovir/emtricitabine at baseline who had taken at least one dose of either raltegravir or ritonavir-boosted protease inhibitors. For the purpose of this analysis, treatment failure was defined as virological failure (confirmed HIV-1 RNA ‡ 50 copies/ ml) or discontinuation of abacavir/lamivudine or tenofovir/emtricitabine because of adverse events, consent withdrawal, or lost to follow-up. There were 143 (72.59%) patients with tenofovir/emtricitabine and 54 (27.41%) with abacavir/lamivudine. In the raltegravir group, there were three (11.11%) treatment failures with abacavir/ lamivudine and eight (10.96%) with tenofovir/emtricitabine (estimated difference 0.15%; 95% CI -17.90 to 11.6). In the ritonavir-boosted protease inhibitor group, there were four (14.81%) treatment failures with abacavir/ lamivudine and 12 (17.14%) with tenofovir/emtricitabine (estimated difference -2.33%; 95% CI -16.10 to 16.70). Triglycerides decreased and HDL cholesterol increased through the study more pronouncedly with abacavir/lamivudine than with tenofovir/emtricitabine and differences in the total-to-HDL cholesterol ratio between both combinations of nucleoside reverse transcriptase inhibitors (NRTIs) tended to be higher in the raltegravir group, although differences at 48 weeks were not significant. While no patient discontinued abacavir/lamivudine due to adverse events, four (2.80%) patients (all in the ritonavir-boosted protease inhibitor group) discontinued tenofovir/emtricitabine because of adverse events ( p = 0.2744). The results of this analysis do not suggest that outcomes of abacavir/lamivudine are worse than those of tenofovir/emtricitabine when combined with raltegravir in virologically suppressed HIV-infected adults.

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Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients

Abstract: In this nonrandomized large cohort, increasing exposure to tenofovir was associated with a higher incidence of CKD, as was true for indinavir and atazanavir, whereas the results for lopinavir/r were less clear.

Cited by 369 publications

References 59 publications

Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

High Prevalence of Signs of Renal Damage Despite Normal Renal Function in a Cohort of HIV-Infected Patients: Evaluation of Associated Factors

Abacavir/Lamivudine Versus Tenofovir/Emtricitabine in Virologically Suppressed Patients Switching from Ritonavir-Boosted Protease Inhibitors to Raltegravir

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