Tenofovir (Viread) is a widely used drug with activity against HIV and hepatitis B virus. Tenofovir is found in the following fixed-dose combinations:
- Truvada – tenofovir + FTC
- Atripla – efavirenz (Sustiva) + tenofovir + FTC
- Complera – rilpivirine (Edurant) + tenofovir + FTC
- Stribild – elvitegravir + cobicistat + tenofovir + FTC
GS-7340, or TAF (tenofovir alafenamide), is a prodrug of tenofovir. Prodrugs are medicines that are converted into their active form once they are processed inside the body. In the case of TAF, it is taken orally and after absorption it passes into the blood. From the blood, TAF is absorbed by cells of the immune system and converted into tenofovir.
The advantage of TAF is that very small amounts of it are needed to exert the same antiviral effect compared to regular tenofovir. Gram for gram, TAF is more potent than regular tenofovir. Preliminary lab experiments with cells and HIV suggest that TAF may be useful against strains of HIV that are resistant to tenofovir.
Results from experiments in people where regular tenofovir (300 mg/day) was compared to TAF (25 mg/day) found that tenofovir reduced viral load by 1.0 log while TAF reduced it by 1.5 logs.
Results from those clinical trials have found that TAF is well tolerated.
Phase III studies of TAF are planned. Eventually TAF will be co-formulated in single-tablet regimens such as the following, where it will replace regular tenofovir:
- elvitegravir + cobicistat + TAF + FTC
- darunavir + cobicistat + TAF + FTC
In lab experiments with cells, TAF has enhanced anti-HIV activity when it is used together with any of the following drugs:
TAF’s greatest enhanced antiviral activity is seen with the class of anti-HIV drugs called integrase inhibitors (dolutegravir, elvitegravir, raltegravir).
TAF is active against many strains, or subtypes, of HIV.
According to Gilead Sciences, the developer of TAF, this drug may also be safer than regular tenofovir. Preliminary results from a phase II clinical trial suggest that compared to regular tenofovir, TAF causes less thinning of bones in the spine. Also, TAF appears to cause less kidney dysfunction. These results will be presented at a medical conference in the future.
—Sean R. Hosein
- Callebaut C, Margot N, Stepan G, et al. Virological profiling of GS-7340, a next-generation tenofovir prodrug with superior potency over tenofovir DF. In: Program and abstracts of the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy, 9-12 September 2012. San Francisco, California. Abstract H-552.
- Gilead Sciences. Gilead’s once-daily novel prodrug for the treatment of HIV meets 24-week primary objective in phase 2 study: data support tenofovir alafenamide fumarate as component of future single tablet HIV regimens. Press release. 31st October, 2012.