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Tenofovir alafenamide equally effective but safer for kidneys and bones than current formulation
Liz Highleyman, 2015-02-27 09:30:00
Tenofovir alafenamide (TAF), a new formulation that has lower concentrations in the blood but reaches higher levels in cells, is as effective as the older version, tenofovir disoproxil fumarate (TDF), according to a report at the Conference on Retroviruses and Opportunistic Infections (CROI 2015) taking place this week in Seattle, USA. A second study showed that TAF has less detrimental effects on the kidneys and bones compared with TDF. TAF has been submitted for approval in Europe and the US.
Gilead Sciences' tenofovir disoproxil fumarate (Viread) is one of the most widely used antiretroviral drugs. It is a component of the Truvada coformulation – used for both HIV treatment and pre-exposure prophylaxis (PrEP) – and of the single-tablet regimens Atripla, Eviplera/Complera and Stribild. TDF is highly potent and generally safe and well-tolerated, but it can cause kidney and bone toxicity in some patients.
TAF is a new pro-drug that delivers the active agent, tenofovir diphosphate, more efficiently to cells infected with HIV. TAF produces adequate intracellular levels with lower doses, which means lower concentrations in the blood plasma and less drug exposure for the kidneys, bones and other organs and tissues. A phase 2 clinical trial previously showed that a regimen of TAF plus emtricitabine, elvitegravir and cobicistat was comparable to TDF/emtricitabine/elvitegravir/cobicistat (Stribild) but caused less kidney impairment and bone loss.
Whereas cheaper, generic versions of tenofovir disoproxil fumarate will be available in many Western markets soon, TAF will be a new product exclusive to Gilead and protected by patent.
David Wohl from the University of North Carolina presented combined primary results from two phase 3 studies (GS-US-292-0104 and GS-US-292-0111) looking at the antiviral activity and overall safety of TAF in a new single-tablet regimen. Paul Sax from Brigham and Women's Hospital in Boston followed the next day with data on TAF's effects on kidneys, bones and lipids.
Study 104 and Study 111 were randomized controlled trials conducted in Europe (both), North America (both), Latin America (Study 111) and Asia (Study 104). Together they included 1733 previously untreated participants with similar characteristics in both trials.
Most (85%) were men, one-quarter were black, 19% were Hispanic/Latino and the median age was 34 years. They had well-controlled HIV disease with a median viral load of 4.58 log10 copies/ml and a median CD4 cell counts of approximately 400 cells/mm3. They had normal kidney function at baseline with a median estimated glomerular filtration rate (eGFR) of approximately 115 ml/min.
Participants were randomly assigned to receive a once-daily single-tablet regimen containing emtricitabine, elvitegravir and cobicistat with either 25mg TAF or 300mg TDF. The primary analysis was done at week 48 of treatment.
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