New Tenofovir Easy on the Kidneys
Little damage with drug designed to prevent renal problems in HIV patients
by Ed Susman
Contributing Writer, MedPage Today
This article is a collaboration between MedPage Today® and: Medpage Today
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Note that these studies were published as abstracts and were presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Tenofovir alafenamide (TAF) -- containing anti-HIV drug regimens, compared with tenofovir disoproxil fumarate (TDF) -- appeared to protect HIV patients at risk of kidney and bone damage.
Note that TAF is a novel prodrug of TFV that has been designed to have less off target effects on the kidneys and other organs, and has demonstrated improved renal and bone safety.
BOSTON -- In a series of deep dives into completed clinical studies, researchers here observed that tenofovir alafenamide -- designed to prevent 'off target' toxicities -- appeared to protect HIV patients at risk of kidney and bone damage.
"Tenofovir alafenamide looks to be a safer drug than tenofovir disoproxil fumarate (Viread)," said David Stein, MD, associate professor of clinical medicine at Albert Einstein College of Medicine, The Bronx. "It you have the opportunity to use it instead of a tenofovir disoproxil fumarate-based regimen, it makes sense to do so. At this point, the bone and the kidney data look fairly compelling."
At the ASM Microbe 2016 meeting, Stein reported on one of the studies which observed that HIV-infected patients who were also diagnosed with diabetes and some chronic kidney disease were able to tolerate with tenofovir alafenamide without further jeopardizing renal function -- and providing efficacy as part of a regimen that suppressed HIV to undetectable levels.
In the study he reported, 242 patients who had been successfully treated with an antiretroviral regimen that suppressed the virus to undetectable levels were switched to the four-drug treatment of elvitegravir, cobicistat/emtricitabine and tenofovir alafenamide.
Of those patients, 33 had been diagnosed with diabetes and their outcomes were compared with the other 209 patients without a diabetes diagnosis. All the patients in the trial had moderate chronic kidney dysfunction, characterized by a glomerular filtration rate of less than 60 mL/min -- 53 mL/min among the diabetics compared with 56 mL/min among the rest of the patients. About two-thirds of the patients had been on a tenofovir disoproxil fumarate-containing regimen before their switch.
Stein explained in his oral presentation that the newer agent has been designed to have less off target effects on the kidneys and other organs, particularly renal tubular cells. After 2 years, participants with impaired renal function and diabetes had stabilized glomerular filtration rates; had significantly reduced reduced total proteinuria and tubular proteinuria, and had nonsignificant reductions in albuminuria.
"These 96-week results support the safety of switching to once daily, single tablet elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide," Stein said.
In the same oral sessions, Cheryl McDonald, MD, an HIV specialist at Tarrant County Infectious Disease Associates, Fort Worth, Texas, illustrated in her report that women who were experiencing renal impairment and were at risk for osteoporosis and loss of bone mineral density appeared to benefit from treatment with tenofovir alafenamide as much as their HIV-infected male counterparts.
The trial compared 50 women and 192 men who were receiving the once-daily elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide regimen. After 96 weeks, the women had increased their spinal bone mineral density 3.58% and the men had increased their bone mineral density at the spine by 1.63%; for hip bone mineral density, the women showed an increase of 2.12% and the men increased their levels 1.78%. All the increased from baseline for both men and women were statistically significant, McDonald reported.
The overall success in suppressing HIV was similar as well, she said. About 90% of the women were also to suppress the virus to undetectable levels as were 88% of the men, using the 50 copies/ml assay.
"In this study of real world HIV-infected women with renal impairment and a median age of 58, excellent virologic suppression was seen at week 96 with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide," McDonald said. "Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide may fulfill a specific unmet need as a potent regimen with improved bone safety for this population."
And in a third presentation with the same theme, Greg Huhn, MD, assistant professor of infectious diseases at the Ruth M. Rothstein CORE Center, Cook County Heath and Hospitals System, Chicago, found safety in using tenofovir alafenamide in patients who were at high risk for chronic renal disease compared with patients who had been on HIV regimens containing tenofovir disoproxil fumarate.
In his study, 959 patients who had been on tenofovir disoproxil fumarate and switched them to the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide treatment, while another 477 patients continued on their original tenofovir disoproxil fumarate-based treatment.
Huhn reported that 2% of the patients treated with the newer drug developed new cases of glomerular filtration rates of less than 60 mL/min while the rate was 3% in these high-risk individuals on tenofovir disoproxil fumarate. Less than 1% of patients on tenofovir alafenamide discontinued treatment due of adverse events, but there were no cases of Fanconi syndrome. By contrast, 1.2% of the patients on tenofovir disoproxil fumarate discontinued due to adverse events, including one case of Fanconi.
At week 96, Huhn said 93% of patients on the tenofovir alafenamide regimen achieved non-detectable viral loads using the 50 copies/mL assay compared with 89% of the patients who stayed on their original tenofovir disoproxil fumarate regimen.
"We found that adults at high-risk for chronic kidney disease who switched to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide experienced a low incidence of chronic kidney disease, did not discontinue due to tubulopathy and achieved significant reductions in proteinuria and tubular proteinuria," he said.
"These results demonstrate the durable efficacy and improved renal safety of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide as a switch regimen for adults with an underlying risk for chronic kidney disease," Huhn said.
The trials were sponsored by Gilead.
McDonald disclosed relevant relationships with Gilead, ViiV, BMS, Janssen, Merck. Speaker's Bureau: Gilead, ViiV, and BMS.
Huhn disclosed relevant relationships with Gilead, ViiV, Janssen, and Bristol-Myers Squibb.
Stein disclosed relevant relationships with Gilead Sciences and Sangamo Biosciences.
Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner 作者: StephenW 时间: 2016-6-23 05:22
At week 96, Huhn said 93% of patients on the tenofovir alafenamide regimen achieved non-detectable viral loads using the 50 copies/mL assay compared with 89% of the patients who stayed on their original tenofovir disoproxil fumarate regimen.
治疗96周，93%的TAF病毒不可测，89%的TDF病毒不可测。
从药效来看，TAF更强一些？
要是这样的话，TAF药效更强，副作用更小，是个不错消息 作者: StephenW 时间: 2016-6-23 09:27