Judd A, Boyd K, Stöhr W, Dunn D, Butler K, Lyall H, et al. Effect of tenofovir disoproxil fumarate on risk of renal abnormality in HIV-1-infected children on antiretroviral therapy: a nested case-control study

MRC Clinical Trials Unit, 222 Euston Road, London, UK.
AIDS (London, England) (Impact Factor: 5.55). 02/2010; 24(4):525-34. DOI: 10.1097/QAD.0b013e3283333680
Source: PubMed


To investigate the association between tenofovir disoproxil fumarate (TDF) use and renal abnormality in a large cohort of HIV-1-infected children on antiretroviral therapy (ART).
Nested case-control study.
Patients were from the Collaborative HIV Paediatric Study, a cohort of approximately 95% of HIV-1-infected children in the UK/Ireland. Serum (but not urine) biochemistry results for 2002-2008 were obtained for 456 ART-exposed children (2-18 years) seen at seven hospitals. Cases had either confirmed hypophosphataemia DAIDS grade at least 2 or estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m; three controls per case were matched by hospital. Conditional logistic regression identified risk factors for renal abnormality.
Twenty of 456 (4.4%) had hypophosphataemia, and one had eGFR less than 60 ml/min per 1.73 m. Ten of 20 (50%) cases versus 11 of 60 (18%) controls had taken TDF-containing ART for a median [interquartile range (IQR)] of 18 [17-20] months, as part of second-line or salvage therapy. The hypophosphataemia incidence rate was 4.3/100 person-years in the TDF group versus 0.9/100 person-years in those not exposed to TDF. In multivariable analysis, only TDF exposure in the previous 6 months was associated with hypophosphataemia [odds ratio (OR) = 4.81, 95% confidence interval (CI) 1.45-16.0, P = 0.01]. In six of 10 children with hypophosphataemia and at least four subsequent phosphate measurements, phosphate values returned to normal when TDF was stopped; in four with three measures or less, values rose but remained subnormal.
Hypophosphataemia was uncommon (4%), but was associated with prolonged TDF use, and was generally reversible following TDF withdrawal. Findings highlight the importance of continuing to monitor longer-term renal function, in particular tubular function, especially in those taking TDF. Further studies assessing urine biochemistry measures which more accurately indicate renal tubular damage are required.

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    • "Furthermore we assessed renal impairment without analyzing urine tests and other more sensitive indicators such as β-2 microglobulinuria that may have shown some milder renal abnormalities. Moreover, we didn't assess the association of TDF and PI with lower bone mineral density as reported by other studies [13,17,33], and the clinical significance of kidney abnormalities observed remains not fully known. Further studies with more sensitive urine markers, bone density assays, and longer follow-up are warranted. "
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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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    • "Despite tenofovir-containing NRTI backbone regimen is effective and well tolerated, the potential for renal toxicity still exists, especially in the patients with vulnerable kidney conditions [5,15,16]. The previous reviews showed that mild tubular impairment is found in a substantial proportion of patients who treated with tenofovir and tends to increase with cumulative exposure [17-21]. However, the onset of tenofovir-associated renal toxicity occurred widely after receiving tenofovir [22]. "
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    ABSTRACT: Background During stavudine phase-out plan in developing countries, tenofovir is used to substitute stavudine. However, knowledge regarding whether there is any difference of the frequency of renal injury between tenofovir/lamivudine/efavirenz and tenofovir/lamivudine/nevirapine is lacking. Methods This prospective study was conducted among HIV-infected patients who were switched NRTI from stavudine/lamivudine to tenofovir/lamivudine in efavirenz-based (EFV group) and nevirapine-based regimen (NVP group) after two years of an ongoing randomized trial. All patients were assessed for serum phosphorus, uric acid, creatinine, estimated glomerular filtration rate (eGFR), and urinalysis at time of switching, 12 and 24 weeks. Results Of 62 patients, 28 were in EFV group and 34 were in NVP group. Baseline characteristics and eGFR were not different between two groups. At 12 weeks, comparing mean ± SD measures between EFV group and NVP group were: phosphorus of 3.16 ± 0.53 vs. 2.81 ± 0.42 mg/dL (P = 0.005), %patients with proteinuria were 15% vs. 38% (P = 0.050). At 24 weeks, mean ± SD phosphorus and median (IQR) eGFR between the corresponding groups were 3.26 ± 0.78 vs. 2.84 ± 0.47 mg/dL (P = 0.011) and 110 (99-121) vs. 98 (83-112) mL/min (P = 0.008). In NVP group, comparing week 12 to time of switching, there was a decrement of phosphorus (P = 0.007) and eGFR (P = 0.034). By multivariate analysis, 'receiving nevirapine', 'old age' and 'low baseline serum phosphorus' were associated with hypophosphatemia at 24 weeks (P < 0.05). Receiving nevirapine and low baseline eGFR were associated with lower eGFR at 24 weeks (P < 0.05). Conclusion The frequency of tenofovir-associated renal impairment was higher in patients receiving tenofovir/lamivudine/nevirapine compared to tenofovir/lamivudine/efavirenz. Further studies regarding patho-physiology are warranted.
    AIDS Research and Therapy 10/2010; 7(1):37. DOI:10.1186/1742-6405-7-37 · 1.46 Impact Factor
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    Hepatology Research 01/2010; 40(1):31-48. DOI:10.1111/j.1872-034X.2009.00597.x · 2.74 Impact Factor
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