If successfully developed and approved by regulatory authorities, the treatment is to offer an option to HIV patients to switch from a standard three-drug therapy to a two-drug, nucleoside reverse transcriptase inhibitor
sparing antiviral regimen.
Rifampicin, a key component of TB treatment, is a potent inducer of drug metabolism and decreases plasma concentrations of many co-administered drugs, including non-nucleoside reverse transcriptase inhibitors
, protease inhibitors and integrase inhibitors.
Reverset was also shown to be effective in patients with virus resistant to other commonly used nucleoside analog reverse transcriptase inhibitors
(NRTIs), including viruses harboring multiple thymidine analog mutations (TAMS), including the M41L and L210W mutations, and the L74V and M184V mutations.
Many people did not achieve durable virologic benefits from these drugs, mainly because they had previously taken and developed resistance to the nucleoside analog reverse transcriptase inhibitors
High AST also was predictive of severe hepatotoxicity in the first 6 months of therapy among patients using a nonnucleoside reverse transcriptase inhibitor
Reverse transcriptase inhibitors
copy the genetic code of HIV and helps it replicate into additional human cells.
Separately, the company signed an agreement with Yamasa Corporation based in Choshi, Japan, to develop EFdA (4'-ethynyl-2-fluoro-2'-deoxyadenosine), a novel nucleoside reverse transcriptase inhibitor
candidate that is in preclinical studies and has shown antiviral activity toward highly resistant HIV strains.
Currently reverse transcriptase inhibitors
represent over 50% of the global sales of HIV drugs which in 2004 was in excess of US$6 billion.
In addition, patients taking a protease inhibitor were more likely to have hyperglycemia compared to patients taking a non-nucleoside reverse transcriptase inhibitor
(NNRTI or "non-nuke").
The randomized study of 122 patients with HIV added a protease inhibitor to a standard regimen of two nucleoside reverse transcriptase inhibitors
and one nonnucleoside reverse transcriptase inhibitor
for 62 patients who continued the induction regimen for 24-32 weeks in order to lower viral load to less than 50 copies/mL.
Today Vitalea Science announced it had received a National Institute of Allergy and Infectious Disease (NIAID) grant to develop and test assays to quantify intracellular uptake of the active metabolite of a nucleoside reverse transcriptase inhibitor
(NRTI) drug that can be applied to children and neonates.
According to Chimerix deal, Merck will have to develope and commercialize CMX157, an investigational oral nucleoside reverse transcriptase inhibitor
which is presently in Phase I clinical development.