Decloedt Eric H, Lesosky Maia, Maartens Gary, Joska John A
Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa.
Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
AIDS Res Ther. 2017 Feb 4;14(1):6. doi: 10.1186/s12981-017-0134-2.
The prevalence of bipolar disorder in HIV-infected patients is higher than the general population. Lithium is the most effective mood stabiliser, while tenofovir disoproxil fumarate (TDF) is frequently used as part of combination antiretroviral therapy (ART). Both TDF and lithium are associated with renal tubular toxicity, which could be additive, or a pharmacokinetic interaction may occur at renal transporters with a decrease in TDF elimination.
We report on the change in estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease formula in participants who received ART including TDF and were enrolled in a 24 week randomised trial of lithium versus placebo in patients with HIV-associated neurocognitive impairment.
We included HIV-infected adults with cognitive impairment established on ART for at least 6 months with a suppressed viral load attending public sector ART clinics in Cape Town, South Africa. We excluded participants with an eGFR <60 mL/min and treated with medications predisposing to lithium toxicity. We reviewed participants weekly for the first month for adverse events followed by 4 weekly visits for renal function assessment, adverse event monitoring and adherence. Lithium dose was titrated to achieve the maintenance target plasma concentration of between 0.6 and 1.0 mmol/L. Sham lithium concentrations were generated for participants receiving placebo.
We included 23 participants allocated to the lithium arm and 30 participants allocated to the placebo arm. Baseline characteristics were not statistically different with a mean age of 37.7 and 40.8 years, a median time on ART of 33 and 40 months and an eGFR of 139.3 and 131.0 mL/min in the lithium and placebo arms respectively. There was no statistical significant difference in the reduction in eGFR or increase in potassium between the two arms during the 24 weeks.
We found that 24-week treatment of HIV-infected patients with lithium and TDF did not result in increased nephrotoxicity. Trial registration The study was registered on the Pan African Clinical Trials Registry (PACTR) with the identifier number PACTR201310000635418. Registered 11 October 2013 before the first participant was enrolled.
HIV感染患者中双相情感障碍的患病率高于普通人群。锂是最有效的情绪稳定剂，而富马酸替诺福韦二吡呋酯（TDF）常用于抗逆转录病毒联合治疗（ART）。TDF和锂均与肾小管毒性有关，这种毒性可能具有累加性，或者在肾转运体处可能发生药代动力学相互作用，导致TDF清除率降低。
我们报告了在接受含TDF的ART治疗且参与一项针对HIV相关神经认知障碍患者进行的锂盐与安慰剂对照的24周随机试验的参与者中，使用肾脏病饮食改良公式估算的肾小球滤过率（eGFR）的变化情况。
我们纳入了在南非开普敦的公共部门ART诊所接受ART治疗至少6个月且病毒载量得到抑制的HIV感染成年认知障碍患者。我们排除了eGFR<60 mL/min且正在接受易导致锂中毒药物治疗的参与者。在第一个月，我们每周对参与者进行不良事件评估，随后每4周进行一次肾功能评估、不良事件监测和依从性检查。锂盐剂量进行滴定以达到0.6至1.0 mmol/L的维持目标血浆浓度。为接受安慰剂的参与者生成假锂盐浓度。
我们纳入了23名分配至锂盐组的参与者和30名分配至安慰剂组的参与者。基线特征无统计学差异，锂盐组和安慰剂组的平均年龄分别为37.7岁和40.8岁，ART治疗的中位时间分别为33个月和40个月，eGFR分别为139.3 mL/min和131.0 mL/min。在24周期间，两组之间eGFR的降低或血钾的升高均无统计学显著差异。
我们发现，对HIV感染患者进行24周的锂盐与TDF联合治疗并未导致肾毒性增加。试验注册 该研究在泛非临床试验注册中心（PACTR）注册，标识符为PACTR201310000635418。于2013年10月11日在首位参与者入组前注册。
