HIV

HIV therapies have advanced substantially in recent years, yet HIV can develop resistance to all current agents and significant drug side effects remain an issue for many patients.   Tenofovir is one of the most widely used antiretrovirals and is part of the Truvada and Atripla fixed dose combinations.  Tenofovir has also been associated with renal toxicity and resistance can be conferred by a single mutation.   Chimerix has made a hexadecyloxypropyl ester of tenofovir (CMX157) with increased activity against both HIV (>250-fold reduction in IC50) and HBV (>4-fold decrease in IC50). 

CMX157 is orally bioavailable in rats and plasma levels above those required for treatment of HIV were attained with a single 10mg/kg dose.  Seven day dosing at 100mg/kg/day in rats revealed no detectable toxicity, suggesting a favorable therapeutic index may be attainable in humans.   By analogy to the hexadecyloxypropyl ester of cidofovir and cidofovir, it is expected that relatively little tenofovir will be secreted into the kidneys when dosing with CMX157 versus dosing with tenofovir.  The greatly reduced IC50 of CMX157 for HIV could also have important implications for resistance.  These data support further development of CMX157 for HIV and possibly for HBV.