A New Nuke in the Works -- GS-9131
Gilead Sciences is developing a new nucleoside analogue (nuke) code-named GS-9131. Once inside of cells, GS-9131 becomes activated by enzymes and turns into a compound with anti-HIV activity called GS-9148. Drugs that are taken in one form and then converted into another form once in the body are called pro-drugs. So far research suggests that GS-9131 (or GS-9148) is not likely to accumulate in kidney cells or harm the parts of the cell that generate power (mitochondria). This is important because older nukes tended to injure mitochondria and cause problems for users. Also, an earlier version of the nuke tenofovir DF (tenofovir disoproxil fumarate) tended to accumulate in the kidneys of some patients and cause kidney dysfunction.
For the rest of this brief report we will refer only to GS-9131 for the sake of simplicity.
Activity Against HIV
There are two main strains of HIV as follows:
- HIV-1 -- the most common strain
- HIV-2 -- a less common strain found mostly in parts of West Africa
HIV-1 can be further subdivided into many subtypes such as A, B, C, D and so on. Subtype B is most commonly found in North America, Central and South America, Western Europe, Japan, Australia and New Zealand. In lab studies with cells and HIV, GS-9131 is active against many subtypes of HIV.
GS-9131 is also active against some strains of HIV that have arisen because of resistance to the following nukes:
- abacavir (Ziagen and in Kivexa and Trizivir)
- emtricitabine (FTC and in Truvada and many other combinations)
- ddI (Videx)
- AZT (Retrovir and in Combivir and Trizivir)
- d4T (Zerit)
- tenofovir DF (Viread and in Truvada and many other combinations)
GS-9131 has increased antiviral activity against HIV when it is combined with the following drugs:
- TAF (tenofovir alafenamide; the new, safer formulation of tenofovir)
- tenofovir DF
- efavirenz (Sustiva, Stocrin and in Atripla)
- darunavir (Prezista and in Prezcobix)
- dolutegravir (Tivicay and in Triumeq)
Thus, GS-9131 may be useful as part of regimens for people who have strains of drug-resistant HIV. Initial clinical trials of this drug should begin in 2017.
White K, Margot N, Stray K, et al. GS-9131 is a novel NRTI with activity against NRTI-resistant HIV-1. Conference on Retroviruses and Opportunistic Infections, 13-16 February 2017, Seattle. Abstract 436.