One of the surprises at CROI 2016 was the first virological data from a new highly potent NRTI that in a slow-release formulation has the potential for annual dosing and that is undergoing research as both treatment and PrEP.
In an oral late-breaker, Jay Grobler from Merck presented results from a dose-ranging study in macaques to develop a model for phase 1 studies with MK-8591 (EFdA).1
Baseline SHIV viral load ranged from 6 to 8 log copies/mL and following single doses that ranged from 3.9 to 18.2 mg/kg viral load dropped by approximately 1.5 logs and was sustained for seven days.
PK data from a phase 1 multiple-dose study in HIV negative adults (using 10 mg, 30 mg and 100 mg) once-weekly for three weeks showed that with the 10 mg dose target intracellular target drug concentrations were exceeded for more than seven days.
A slightly cheeky slide was shown from the phase 1b study showing that EFdA produced more rapid viral suppressions compared to historical data for TDF and TAF.
Early data on a solid-state slow release parenteral injection formulation that has an option for removability, showed sustained release for more than 180 days in rat studies, with the potential for cover to be extended to a year.
was -0.4 (-4.7, 4.5) mL/min, eGFR-cystatin C 3.8 (-4.8, 11.2) mL/min/1.73m2, and aGFR (n=32, 68.8% TDF at baseline) was 0.1 (-4.3, 4.4) mL/min, indicating that GFR was not affected by E/C/F/TAF. Two subjects (0.8%) discontinued study drug for decreased GFR by eGFRC-G and eGFR-cystatin C, neither with evidence of renal tubulopathy. The prevalence of clinically significant proteinuria (UPCR > 200 mg/g) and albuminuria (UACR ≥ 30 mg/g) decreased from 42% to 21% and 49% to 27%, respectively. Significant decreases in urine retinol binding protein to creatinine ratio, beta”‘2”‘microglobulin to creatinine ratio, and fractional excretion of uric acid were observed (p