GS-7340 : Tenofovir Prodrug Requires Lower Doses, But Will It Be
Friendlier on Kidney and Bones?
CROI 2012- Oral Presentation #103. GS-7340 25 mg and 40 mg Demonstrate
Superior Efficacy to Tenofovir 300 mg in a 10-day Monotherapy Study of HIV-1+
GS-7340 is a novel
prodrug of tenofovir (TVF) that has shown greater antiviral activity at lower
doses than tenofovir disoproxil fumarate (TDF) 300 mg, achieving higher
intracellular TFV-diphosphate (DP) concentration with lower systemic TFV
exposure, in a prior proof-of-concept study.
This randomized, partially blinded, placebo and
active-controlled, dose-finding, 10-day monotherapy study was conducted to
compare 3 different doses of GS-7340 (8, 25, and 40 mg once daily), open-label
TDF (300 mg once daily), and GS-7340 placebo in HIV-1-infected subjects with
HIV-1 RNA ≥2000 copies/mL, no genotypic resistance to TDF, and CD4 cell count
≥200 cells/mm3. The primary endpoint was time-weighted average HIV-1 RNA change
from baseline after 10 days of treatment. Plasma and intracellular peripheral
blood mononuclear cell pharmacokinetics
were also assessed.
The study found that GS-7340
at 25 mg and 40 mg demonstrated superior antiviral efficacy to TDF at 300 mg,
achieving higher intracellular TFV-DP concentration with lower systemic TFV
exposure. GS-7340 has the potential to be more efficacious with an improved
safety margin, and to be easier to co-formulate, compared with TDF. A later presentation also showed that this
prodrug has better penetration in different body compartments compared to
Let’s hope that this
pro drug will show less of a negative effect on kidney function and bone
density than tenofovir. Let’s also hope
that its better tissue penetration is different body compartments will also
result in better control of latent HIV infection in reservoirs.