Kirby Institute, University of New South Wales, Sydney, NSW, Australia; NewYork-Presbyterian/Weill Cornell Medical Center, New York, NY, USA.
University College London, London, UK.
Int J Antimicrob Agents. 2017 Sep;50(3):453-460. doi: 10.1016/j.ijantimicag.2017.04.021. Epub 2017 Jun 28.
The impact of early ART initiation (versus deferring) on kidney function has not been studied. START was a randomised comparison of immediate versus deferred ART initiation among HIV-positive persons with CD4 (cells/mm) counts >500. Serum creatinine and urine dipstick protein were measured at Months 0, 1, 4, 8 and 12, and annually thereafter. The two arms were compared for changes in eGFR (mL/min/1.73 m, calculated by CKD-EPI equation), over time using longitudinal mixed models. Of 4685 START participants, 4629 (2294 in immediate and 2335 deferred arm) were included. Median baseline CD4 and eGFR were 651 and 111.5, respectively. ART was initiated in 2271 participants (99.0%) in the immediate and 1127 (48.3%) in the deferred arm, accounting for >94% and >19% of follow-up time, respectively. Overall, 89% started ART using a tenofovir-based regimen. Over 2.1 years median follow-up, mean eGFR was 0.56 (95% CI 0.003-1.11) higher in the immediate versus deferred arm, which was more prominent after adjustment for current tenofovir or bPI use (1.85, 95% CI 1.21-2.50) and in Black participants (30.1% overall) (3.90, 95% CI 2.84-4.97) versus non-Blacks (1.05, 95% CI 0.33-1.77) (P < 0.001 for interaction). Relative risk for proteinuria in the immediate versus deferred arm was 0.74 (95% CI 0.55-1.00) (P = 0.049). In the short-term, immediate ART initiation was associated with a modestly higher eGFR and lower proteinuria risk versus deferring ART (more pronounced in Black participants). Whether this early benefit translates into a lower risk of CKD requires further follow-up.
早期开始 ART（与延迟相比）对肾功能的影响尚未研究。START 是一项在 CD4（细胞/mm）计数>500 的 HIV 阳性者中比较立即开始与延迟开始 ART 的随机对照比较。在 0、1、4、8 和 12 个月以及此后每年测量血清肌酐和尿液试纸蛋白。使用纵向混合模型比较两个手臂的 eGFR（mL/min/1.73m，通过 CKD-EPI 方程计算）随时间的变化。在 4685 名 START 参与者中，4629 名（立即组 2294 名，延迟组 2335 名）被纳入分析。中位基线 CD4 和 eGFR 分别为 651 和 111.5。在立即组和延迟组中，分别有 2271 名（99.0%）和 1127 名（48.3%）参与者开始 ART，分别占随访时间的>94%和>19%。总体而言，89%的人使用基于替诺福韦的方案开始 ART。在 2.1 年的中位随访期间，与延迟组相比，立即组的 eGFR 平均高 0.56（95%CI 0.003-1.11），调整当前使用替诺福韦或 bPI 后更为明显（1.85，95%CI 1.21-2.50），并且在黑人参与者（总体 30.1%）中更为明显（3.90，95%CI 2.84-4.97），而非黑人参与者（1.05，95%CI 0.33-1.77）（P<0.001 交互作用）。立即组与延迟组相比蛋白尿的相对风险为 0.74（95%CI 0.55-1.00）（P=0.049）。在短期内，与延迟 ART 相比，立即开始 ART 与 eGFR 适度升高和蛋白尿风险降低相关（在黑人参与者中更为明显）。这种早期获益是否会降低 CKD 风险还需要进一步随访。
