genvoya approved by FDA

the FDA just approved a new single pill for the treatment of HIV-1. Genvoya (the new drug) is basically the same drug as Stribild (elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg and tenofovir disoproxil fumarate, or TDF,  300mg), but changes the TDF to tenofovir alafenamide 10mg (TAF). This is really a good evolution, since data over the last few years has confirmed that TAF has similar antiviral efficacy to TDF but much less renal toxicity and bone loss. The current FDA approval is for HIV-1 patients who are treatment-naive, over 12 years old, weighing more than 35 kg, as well as for adults with suppressed viral loads (<50 copies/ml) on a stable antiretroviral regimen.  TAF has a much lower tenofovir dose than TDF, has lower blood levels, but higher intracellular levels (where the HIV-1 replicates). There is an accompanying boxed-warning that it can cause lactic acidosis and severe hepatomegaly with steatotosis, either of which can be fatal, and that it is not approved to treat hepatitis B infection. Common side effect is nausea. Genvoya is not recommended for patients with severe renal impairment (undefined), though can be used in those with moderate renal impairment. The European Union also approved its use in September. For the full but brief FDA press release, see http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm471300.htm​ .

a couple of comments:

--though the FDA warned against using Genvoya for hepatitis B, there are actually some small studies finding TAF is as good as TDF for treating hepatitis B (see Journal of Hepatology, 2015-03-01, Volume 62, Issue 3, Pages 533-540).  ie, my guess is that they mean that we should not use Genvoya for sole hepatitis B infections, though it does sound reasonable to me to use Genvoya for those with a combo of HIV and hepatitis B (as i have been doing with prior HIV regimens that have TDF/FTC as a component). but i would follow the hepatitis B viral load closely, just to be sure.

--my understanding is that the FDA approval was based on a few studies, including a non-inferiority study just released in the Lancet Infectious Diseases journal. There they looked at 1443 patients who were on one of 4 TDF-based regimens, were virologically suppressed, and had eGFR >50 ml/min, then randomized them to either the combo of elvitegravir/cobicistat/emtricitabine/TAF (ie. Genvoya) vs continuing their prior meds (see hiv TAF vs TDF lancet infdis 2015 in dropbox, or doi.org/10.1016/S1473-3099(15)00348-5). bottom line: at 48 weeks, viral suppression with Genvoya was 97%, vs 93% if continued their old meds. hip and spine bone mineral density, as well as GFR and proteinuria, were better with TAF (Genvoya) than in those on the TDF-based meds, though there were more adverse events in the TAF group (mostly not related to the drug, such as URIs, with somewhat fewer Grade 3 or 4 adverse events -- 9% vs 11% with TDF). Nausea was present in 5% of those on Genvoya.

--so, finally, TAF will be hitting the approved-drug lists. hopefully in other forms as well (eg, just replacing the TDF in Truvada, which is TDF and emtricitabine, with TAF).  we'll see what the cost will be....​

for other blogs on tenovofir in HIV, see:

http://gmodestmedblogs.blogspot.com/2015/04/updated-hiv-guidelines-2015.html which reviews the current guidelines and highlights stribild as one of the preferred initial drugs

http://gmodestmedblogs.blogspot.com/2015/06/tenofovir-nephrotoxicity.html  which comments on how best to screen for tenofovir nephrotoxicity