Early safety of tenofovir alafenamide in patients with a history of tubulopathy on tenofovir disoproxil fumarate: a randomized controlled clinical trial

被引：10

作者：

Hamzah, L. ^{[1
]}

Williams, D. ^{[2
]}

Bailey, A. C. ^{[3
]}

Jones, R. ^{[4
]}

Ibrahim, F. ^{[5
]}

Musso, C. G. ^{[6
]}

Burling, K. ^{[7
]}

Barbini, B. ^{[8
]}

Campbell, L. ^{[8
]}

Post, F. A. ^{[5
,8
]}

Hamzah, Lisa ^{[9
]}

Campbell, Lucy ^{[9
]}

Adegbaju, Oluwayomi ^{[9
]}

Engler, Birgit ^{[9
]}

Bhagwandin, Priya ^{[9
]}

Santana-Suarez, Beatriz ^{[9
]}

Post, Frank ^{[9
]}

Johnson, Margaret ^{[10
]}

Hemat, Nargis ^{[10
]}

Ngwu, Nnenna ^{[10
]}

Nightingale, Alice ^{[10
]}

Edwards, Jonathan ^{[10
]}

Fernandez, Thomas ^{[10
]}

Williams, Deborah ^{[2
]}

Richardson, Celia ^{[2
]}

Campbell, Marion ^{[2
]}

Trevitt, Vittorio ^{[2
]}

Jones, Rachael ^{[11
]}

Fedele, Serge ^{[11
]}

Bisdomini, Elisa ^{[11
]}

Montauri, Laura ^{[11
]}

Thunder, Orla ^{[11
]}

Morrish, Thomas ^{[11
]}

Soler-Carracedo, Alfredo ^{[11
]}

Martinez-Berlanga, Andrea ^{[11
]}

Bailey, Angela ^{[12
]}

Alagaratnam, Jasmini ^{[12
]}

Legg, Ken ^{[12
]}

Petersen, Claire ^{[12
]}

Clift, Paul

Cromarty, Ben

机构：

[1] St Georges Healthcare NHS Trust, London, England

[2] Brighton & Sussex Univ Hosp, Brighton, E Sussex, England

[3] Imperial Coll Healthcare NHS Trust, London, England

[4] Chelsea & Westminster Hosp NHS Fdn Trust, London, England

[5] Kings Coll London, London, England

[6] Italian Hosp, Buenos Aires, DF, Argentina

[7] NIHR Cambridge Biomed Res Ctr, Core Biochem Assay Lab, Cambridge, England

[8] Kings Coll Hosp NHS Fdn Trust, Weston Educ Ctr Rm 2-53,Cutcombe Rd, London SE5 9RJ, England

[9] Kings Coll Hosp London, London, England

[10] Royal Free Hosp, London, England

[11] Chelsea & Westminster Hosp, London, England

[12] Imperial Healthcare NHS Trust, London, England

来源：

HIV MEDICINE | 2020年 / 21卷 / 03期

关键词：

Fanconi; kidney; tenofovir alafenamide; tenofovir disoproxil fumarate; tubulopathy; FANCONI SYNDROME; KIDNEY-DISEASE; RENAL-FUNCTION; HIV; EMTRICITABINE; ELVITEGRAVIR; COBICISTAT; BONE;

D O I：

10.1111/hiv.12819

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Objectives The aim of the study was to assess the effect of tenofovir alafenamide (TAF) on kidney and bone biomarkers in patients who developed proximal renal tubulopathy (PRT) while receiving tenofovir disoproxil fumarate (TDF). Methods Individuals with a history of TDF-associated PRT and currently suppressed HIV infection on a tenofovir-sparing regimen were randomized 1:1 to continue current antiretroviral therapy or initiate emtricitabine (F)/TAF with discontinuation of nucleoside reverse transcriptase inhibitors (NRTIs) as appropriate. Renal and bone biomarkers were analysed at baseline, week 4 and week 12. The primary outcome was the mean difference between study arms in urine retinol-binding protein:creatinine ratio (RBPCR) change from baseline to week 12. Data were analysed using linear regression, with robust standard errors (primary outcome), and repeated measures mixed effects models (secondary outcomes). The trial was registered under European Union Drug Regulating Authorities Clinical Trials Database 2016-003345-29. Results We randomized 31 individuals [mean age 52.4 (standard deviation 0.3) years; 97% male; 90% white); all completed the study. At 12 weeks, there was no difference in change in RBPCR (beta 19.6; 95% confidence interval -35.3, 74.5; P = 0.47), and no difference in change in estimated glomerular filtration rate (eGFR) (based on creatinine or cystatin C), albuminuria, proteinuria, renal phosphate or urea handling, (fasting) urine osmolality, parathyroid hormone and bone turnover markers in the control versus the F/TAF exposed groups. No cases of PRT were observed. Conclusions In people with a history of proximal renal tubulopathy while on TDF, 12-week exposure to TAF did not adversely affect renal tubular function. These data support continued evaluation of the long-term safety of TAF in this group of patients.

引用

页码：198 / 203

页数：6

共 23 条

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