MRC Clinical Trials Unit, 222 Euston Road, London, UK.
AIDS. 2010 Feb 20;24(4):525-34. doi: 10.1097/QAD.0b013e3283333680.
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.
在接受抗逆转录病毒治疗（ART）的大量 HIV-1 感染儿童队列中，研究替诺福韦二吡呋酯（TDF）的使用与肾脏异常之间的关联。
巢式病例对照研究。
患者来自协作性 HIV 儿科研究，这是英国/爱尔兰约 95% HIV-1 感染儿童的队列。为了对 7 家医院就诊的 456 名接受 ART 暴露的儿童（2-18 岁）进行研究，获得了 2002-2008 年血清（而非尿液）生化结果。病例具有以下任何一种情况：至少达 DAIDS 等级 2 的确诊低磷血症，或肾小球滤过率（eGFR）<60ml/min/1.73m2；每个病例匹配 3 名医院对照。条件逻辑回归确定了肾脏异常的危险因素。
456 例中，有 20 例（4.4%）患有低磷血症，1 例 eGFR<60ml/min/1.73m2。20 例病例中，有 10 例（50%）接受 TDF 含药 ART 治疗，中位（IQR）为 18 [17-20]个月，为二线或挽救治疗的一部分。TDF 组的低磷血症发生率为 4.3/100 人年，而未接触 TDF 的患者为 0.9/100 人年。多变量分析显示，仅在过去 6 个月内接触 TDF 与低磷血症相关[比值比（OR）=4.81，95%置信区间（CI）1.45-16.0，P=0.01]。在 10 例低磷血症患儿中，有 6 例在停止 TDF 后磷酸盐值恢复正常，且至少有 4 次磷酸盐检测值；4 例有 3 次或更少的测量值，值有所上升，但仍低于正常值。
低磷血症并不常见（4%），但与长期 TDF 应用有关，停药后通常可恢复正常。这些发现强调了继续监测更长期肾功能的重要性，特别是在服用 TDF 的患者中，尤其要监测肾小管功能。需要进一步的研究来评估更准确地指示肾小管损伤的尿液生化指标。
