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. A second study showed that the TAF has less harmful effects on the kidneys and bones compared with TDF. TAF has been submitted for approval in Europe and the USA.
Tenofovir disoproxil fumarate (Viread) Gilead Sciences, is one of antiretroviral drugs most widely used. Coformulation is a component of Truvada - used to treat HIV and pre-exposure prophylaxis (PrEP) - and single dose treatment regimens Atripla Eviplera, and Complera Stribild. TDF is highly potent and generally safe and well tolerated, but 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, meaning less blood plasma concentration and less exposure of drug to the kidneys, bones and other organs and tissues. A clinical trial phase 2 previously showed that a TAF system more emtricitabine, and elvitegravir cobicistat was comparable PTO elvitegravircobicistat emtricitabine (Stribild), but caused less loss of bone and kidney impairment.
Whereas cheaper versions, generic tenofovir disoproxil fumarate are available in many Western markets soon, TAF will be a new and unique product Gilead patent protected.
David Wohl University of North Carolina primary results showed the combined two-stage studies 3 (GS-US-292-0104 and GS-US-292-0111) observing the antiviral activity and there is total security in a system if a one tablet diáriocomo the new TAF. Paul Sax from Brigham and Womens Hospital in Boston coduziu the next day, a study report with data on the effects of TAF on the kidneys, bones and lipids.
The 104 and 111 studies were randomized, conducted in Europe (both), North America (both), Latin America (111) and Asia (study 104). Together, they included participants 1733 previously treated with similar characteristics in both trials.
Most (85) were men, a 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 4,58 log10 copiesml CD4 and a median score in about 400 mm3 cells per blood. They had normal renal function at baseline with a glomerular filtration rate estimated median (eGFR) of approximately 115 ml / min.
Participants were randomized to receive a regimen of one tablet once a day containing emtricitabine, elvitegravir and cobicistat with 10mg TAF or 300mg TDF. The primary analysis was done on the forty-eighth week of treatment.
Overall effectiveness and safety results
Both systems had similar high efficacy, demonstrating that the co-formulation TAF is not less than the co-formulation with TDF. In 48 weeks, 92 people in TAF and 90 arm in arm TDF achieved viral suppression (HIV RNA <50 copies ml) in the combined analysis (93 92 vs study 104, 92 89 vs study 111). CD4 cell gains were also similar in 211 cells / mm3 in TAF arm and 181 mm3 cells in the TDF arm.
Viral suppression rates for the TAF and TDF regimens were similar regardless of whether participants had high viral load or low baseline, CD4 counts above or below 200 sex cells / mm3, man or woman, whether black or not and greater or lesser 50 years old.
In both studies, 4 of participants experienced treatment failure. Among the small number (2) who met the criteria for the stress tests, very few in the arms showed evidence of any primary resistance mutations (0.8 with TAF, 0.6 with TDF).
The treatment was generally safe and well tolerated. According to Dr Wohl were presented overall safety profile of the drug, which was similar in both arms. There was 45 patients (5) the TAF and 71 arm (8) in the TDF arm discontinued treatment early, including people of 8 and 13, respectively, who were forced to leave the study because of adverse events.
About 40 participants experienced adverse effects caused by the drug, mild to moderate. The most common side effects were diarrhea (18), nausea (16) and headache, all occurring frequently similar in both groups. In the arms TAF and TDF and were few serious adverse events (8 against 7) or even discontinuation of administration of the study drug for this reason (0,9 vs 1.5); 20 3 or laboratory abnormalities 4 class in both groups.
Nothing stood out in terms of association of adverse events with TAF that has not been seen with TDF, Wohl said.
Published: 27 February 2015 in http://www.aidsmap.com/Tenofovir-alafenamide-equally-effective-but-safer-for-kidneys-and-bones-than-current-formulation/page/2949354/
Translated By Claudio Souza, with support from Tradukka
Editor's Note: I usually do some cometary on the news that post. However, since you are here, I suggest you read the link that turns below and notice how Gilead (a large pharmaceutical laboratory in search of solutions for a better life) "squeezes every last drop their" lemons "in another text, translated by Rodrigo S. Pellegrine:
"It's time for Tenofovir 2.0" Pay close attention to what I highlighted in red
|The certificate has also been included in our secure, probable, audit trail. Details of this certificate are published athttp://www.digiprove.com/show_certificate.aspx?id=600574&guid=sxXmN3-Bl0OHWMAMMVXGOg.|