Tenofovir Alafenamide (TAF) in People With Kidney Dysfunction
As mentioned previously in this issue of TreatmentUpdate, clinical trials assessing the new formulation of tenofovir (tenofovir alafenamide, or TAF) and sometimes comparing it to the original formulation (tenofovir disoproxil fumarate, or TDF) are ongoing. Studies have found that TAF is as effective as TDF and is very likely safer, particularly for the kidneys and bones. Participants enrolled in these studies had relatively good kidney health.
But will TAF be safe in people with pre-existing kidney dysfunction? To try to answer this question, researchers conducted study 292-0112. In this study, researchers sought participants who had mild-to-moderate kidney dysfunction graded with the use of eGFR (estimated glomerular filtration rate). After screening, researchers recruited 242 HIV-positive participants who had an eGFR between 30 and 69 mL/minute, who were on stable combination anti-HIV therapy (commonly called ART) and who had a viral load less than 50 copies/ml. All participants were switched to a TAF-containing regimen and monitored for 48 weeks. In general, TAF was safe and when this formulation of tenofovir was substituted for TDF, improvements in bone density and kidney health were seen. However, not every participant who switched from TDF to TAF had improvement in kidney injury, particularly in cases of severe injury to these organs.
All 242 participants were switched from their current regimen to the following regimen:
The average profile of participants when they entered the study was as follows:
Overall, 158 participants were taking TDF as part of their regimen and 84 participants were taking other nukes.
In the everyday world outside a clinical trial, when assessing kidney health, doctors usually request lab analyses of blood, and in particular the amount of the waste product creatinine. They can then put the amount of creatinine detected into a formula and get an estimate of the functioning of the kidneys. This is called the estimated glomerular filtration rate (eGFR). Doctors routinely use eGFR because assessing the actual GFR (written as aGFR) would be cumbersome for patients. Note that the eGFR is an estimate and it is useful for routine laboratory analyses requested by doctors.
However, in the present research setting, it was important to find out about the aGFR because eGFR is a calculated value (not a measured one). In the present study, researchers were able to assess the actual GFR. They found that there were no significant changes in the aGFR and only minor ones with eGFR after participants switched to a TAF-based regimen. Overall, this suggests that TAF does not have a major impact on the kidneys' ability to filter blood.
The researchers also had laboratories analyse participants' urine and they assessed certain proteins in the urine, as follows:
They found significant reductions in these proteins among TAF users but not TDF users. Overall, this suggests that TAF helped to reduce kidney injury compared to TDF.
A Moderate-to-Severe Degree of Kidney Injury
Researchers focused on people with high levels of total protein in their urine samples (more than 200 mg/gram,) as this sub-group would likely have a higher level of kidney injury than other participants.
Switching From TDF to TAF
In conducting their analyses, researchers found that among participants who had been on a TDF-containing regimen at the start of the study, 47% had high levels of protein in their urine, suggestive of kidney injury. After switching from TDF to TAF, 48 weeks later the proportion with a high level of protein in their urine was 13%. This difference was statistically significant. It shows that switching from TDF to TAF is associated with significant improvements in kidney health. However, note that this switch does not help everyone who used TDF. Perhaps not everyone's kidneys recovered after the switch because of the severity of kidney injury, or there may have been other factors that could have affected kidney health that were unrelated to TAF, such as the presence of higher-than-normal blood pressure, type 2 diabetes and so on.
This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication TreatmentUpdate. Visit CATIE's Web site to find out more about their activities, publications and services.
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