AIDS InfoNet www.aidsinfonet.org Fact Sheet Number 410 NUCLEOSIDE ANALOG REVERSE TRANSCRIPTASE INHIBITORS IN DEVELOPMENT NOTE: several fact sheets describe NUCLEOSIDE ANALOGS drugs that are being tested against HIV: (NUKES) IN DEVELOPMENT by Inc is active  Fact sheet 430: non-nucleoside against HIV and hepatitis B in analog reverse transcriptase inhibitors (ATC, AVX754) by Avexa. laboratory studies. In a Phase I/II (NNRTIs or non-nukes) A meeting with the FDA in early 2011 study, Racivir showed anti HIV activity  Fact sheet 440: protease inhibitors discussed results from Phase II/III that lasted more than 2 weeks after the  Fact sheet 460: attachment and studies. Avexa is proceeding with its drug was stopped. The makers hope fusion inhibitors development. that Racivir can be used as a once-daily  Fact sheet 470: new classes of drug. antiviral drugs CMX157 by Chimerix is a version of  Fact sheet 480: immune therapies tenofovir with better properties in the body. It has completed a Phase I trial. These drugs have not been approved by the Food and Drug Administration (DFC), formerly (FDA) for use against HIV. known as Reverset, is being developed NUKES NO LONGER IN by Pharmasset. DFC is taken as a pill, DEVELOPMENT once a day. It has shown activity The following drugs are no longer being against HIV with resistance to various developed for use against HIV: NUCLEOSIDE ANALOG antiretroviral drugs. REVERSE TRANSCRIPTASE  Adefovir dipivoxil (bis POM PMEA) by Gilead Sciences INHIBITORS DOT (Dioxolane thymidine) is being studied by the University of Georgia in  (MIV-310, FLT) by These drugs stop HIV from multiplying Phase I trials. Boehringer Ingelheim and Medivir by blocking the reverse transcriptase  DAPD () by RFS Pharm enzyme. This enzyme changes HIV’s (ACH-126,443, Fd4C) by was discontinued in 2010 genetic material (RNA) into the form of Achillion Pharmaceuticals is a once-  dOTC (BCH-10652, BCH-10618) DNA. This step has to occur before daily drug with activity against HIV that by BioChem Pharma HIV’s genetic code gets combined with is resistant to several other nukes. It is an infected cell’s own genetic codes.  FddA (Beta-fluoro-ddA, also effective against hepatitis B. It has The nucleoside analogs (often called ) by US Bioscience successfully completed one year of a “nukes”) mimic the building blocks used  GW420867X by GlaxoSmithKline Phase II study. by reverse transcriptase to make copies  Lobucavir by Bristol-Myers Squibb of the HIV genetic material. These fake  SPD756 by Shire Pharmaceuticals Festinavir (E-d4T, OBP-601) by building blocks disrupt the copying. Bristol-Myers Squibb showed good

results in a Phase I trial. It may be a

once-daily drug.

GS7340 is a new version of tenofovir. It is a “prodrug” of tenofovir: when it is broken down in the body, it produces tenofovir. Phase Ib study results showed it is much more potent than tenofovir and may have fewer side effects.

MIV-210 (FLG) by GlaxoSmithKline and Medivir shows good activity against HIV with resistance to other nukes. It is in Phase I trials. Revised April 4, 2011

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