Mwafongo Albert, Nkanaunena Kondwani, Zheng Yu, Hogg Evelyn, Samaneka Wadzanai, Mulenga Lloyd, Siika Abraham, Currier Judith, Lockman Shahin, Hughes Michael D, Hosseinipour Mina
aUniversity of North Carolina Project, Kamuzu Central Hospital, Lilongwe bJohns Hopkins Project, Queen Elizabeth Central Hospital, Blantyre, Malawi cHarvard School of Public Health, Boston, Massachusetts dSocial & Scientific Systems, Inc., Silver Spring, Maryland, USA eUZ-UCSF Collaborative Research Programme, Harare, Zimbabwe fCenter for Infectious Disease Research, Lusaka, Zambia gMoi University (College of Health Sciences), Eldoret, Kenya hUniversity of California, Los Angeles, Los Angeles, California iBrigham and Women's Hospital, Boston, Massachusetts jUniversity of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.
AIDS. 2014 May 15;28(8):1135-42. doi: 10.1097/QAD.0000000000000202.
Tenofovir disoproxil fumarate (TDF) has been associated with renal insufficiency. Co-administration with boosted protease inhibitors, which increases its exposure, may further increase the risk of renal insufficiency.
We compared the incidence of renal events among women taking TDF co-administered with lopinavir/ritonavir (LPV/r) versus those co-administering TDF with nevirapine (NVP). Renal events were defined as a confirmed drop in creatinine clearance associated with a serum creatinine grade 2 or higher, or that leading to treatment modification.
Overall, 741 HIV-infected women were enrolled into the study. Of these, 24 (3.2%) had reportable renal events (18 in LPV/r arm, six in NVP arm). In multivariate analysis, renal events were significantly associated with the LPV/r arm [odds ratio (OR) 3.12, 95% confidence interval (CI) 1.21, 8.05; P = 0.019], baseline HIV-1 RNA (OR 2.65, 95% CI 1.23, 5.69 per 1 log10 copies/ml higher; P = 0.013) and baseline creatinine clearance (OR 0.83, 95% CI 0.70-0.98 per 10 ml/min higher; P = 0.030). In multivariate analysis evaluating renal events requiring treatment modification, only baseline HIV-1 RNA and creatinine clearance were significantly associated (OR 4.41, 95% CI 1.65, 11.78 per 1 log10 copies/ml higher; P = 0.003 and OR 0.80, 95% CI 0.64, 0.99 per 10 ml/min higher; P = 0.040, respectively).
The rates of renal events were relatively low in the two treatment arms. However, patients taking TDF co-administered with LPV/r had significantly more renal events compared to those co-administered with NVP. Furthermore, higher baseline HIV RNA and lower creatinine clearance were associated with the development of renal insufficiency requiring treatment modification.
富马酸替诺福韦二吡呋酯（TDF）与肾功能不全有关。与增强型蛋白酶抑制剂合用会增加其暴露量，可能进一步增加肾功能不全的风险。
我们比较了服用TDF并联合洛匹那韦/利托那韦（LPV/r）的女性与服用TDF并联合奈韦拉平（NVP）的女性中肾脏事件的发生率。肾脏事件定义为肌酐清除率确诊下降且血清肌酐分级为2级或更高，或导致治疗调整。
总体而言，741名感染HIV的女性被纳入研究。其中，24名（3.2%）发生了可报告的肾脏事件（LPV/r组18名，NVP组6名）。在多变量分析中，肾脏事件与LPV/r组显著相关[比值比（OR）3.12，95%置信区间（CI）1.21，8.05；P = 0.019]、基线HIV-1 RNA（OR 2.65，95%CI 1.23，5.69每高1 log10拷贝/ml；P = 0.013）和基线肌酐清除率（OR 0.83，95%CI 0.70 - 0.98每高10 ml/min；P = 0.030）。在评估需要治疗调整的肾脏事件的多变量分析中，只有基线HIV-1 RNA和肌酐清除率显著相关（OR 4.41，95%CI 1.65，11.78每高1 log10拷贝/ml；P = 0.003和OR 0.80，95%CI 0.64，0.99每高10 ml/min；P = 0.040）。
两个治疗组的肾脏事件发生率相对较低。然而，与联合NVP的患者相比，服用TDF并联合LPV/r的患者发生的肾脏事件明显更多。此外，更高的基线HIV RNA和更低的肌酐清除率与需要治疗调整的肾功能不全的发生有关。
