NUCLEOSIDE ANALOG REVERSE TRANSCRIPTASE INHIBITORS IN DEVELOPMENT

NOTE: Several fact sheets describe drugs that are being tested against HIV: These drugs have not been approved by the Food and Drug Administration (FDA) for use against HIV.
NUCLEOSIDE ANALOG REVERSE TRANSCRIPTASE INHIBITORS
These drugs stop HIV from multiplying by blocking the reverse transcriptase enzyme. This enzyme changes HIV's genetic material (RNA) into the form of DNA. This step has to occur before HIV's genetic code gets combined with an infected cell's own genetic codes. The nucleoside analogs (often called "nukes") mimic the building blocks used by reverse transcriptase to make sopies of the HIV genetic material. These fake building blocks disrupt the copying.
NUCLEOSIDE ANALOGS (NUKES) IN DEVELOPMENT
Nucleoside analogs (nukes) in development include Apricitabine, DAPD, DOT, Elvucitabine, KP-1461, MIV-21 (FLG) and Racivir.

Apricitabine (AVX754) by Avexa (formerly SPD754 by Shire Pharmaceuticals) has shown good activity against HIV that is resistant to 3TC (Epivir). It is in Phase II studies. Apricitabine seems well tolerated.

DAPD (amdoxovir) is being developed by RFS Pharm. It is in Phase II studies. Some eye problems were detected in early studies and are being studied carefully.

DOT (Dioxolane thymidine) is being studied by the University of Georgia in Phase I trials.

Elvucitabine (ACH-126,443, Fd4C) by Achillion Pharmaceuticals is a once-daily drug with activity against HIV that is resistant to several other nukes. It is also effective against hepatitis B. It is in Phase II studies.

KP1461 by Koronis is a prodrug of Koronis KP-1212. It introduces mutations into HIV that become lethal. It is in Phase I trials.

MIV-210 (FLG) by GlaxoSmithKline and Medivir shows good activity against HIV with resistance to other nukes. It is in Phase I trials.

Racivir by Pharmasset Inc is active against HIV and hepatitis B in laboratory studies. In a Phase I/II study, Racivir showed anti HIV activity that lasted more than 2 weeks after the drug was stopped. The makers hope that Racivir can be used as a once-daily drug.

NUKES NO LONGER IN DEVELOPMENT
The following drugs are no longer being developed for use against HIV:

  • Adefovir dipivoxil (bis POM PMEA) by Gilead Sciences
  • Alovudine (MIV-310, FLT) by Boehringer Ingelheim and Medivir
  • DFC (Dexelvucitabine, formerly known as Reverset) by Incyte Corporation
  • dOTC (BCH-10652, BCH-10618) by BioChem Pharma
  • FddA (Beta-fluoro-ddA, Lodenosine®) by US Bioscience
  • GW420867X by GlaxoSmithKline
  • Lobucavir by Bristol-Myers Squibb
  • SPD756 by Shire Pharmaceuticals