<p> AIDS InfoNet www.aidsinfonet.org Fact Sheet Number 410 NUCLEOSIDE ANALOG REVERSE TRANSCRIPTASE INHIBITORS IN DEVELOPMENT</p><p>NOTE: several fact sheets describe NUCLEOSIDE ANALOGS drugs that are being tested against (NUKES) IN DEVELOPMENT HIV: Racivir by Pharmasset Inc is active  Fact sheet 430: non-nucleoside Apricitabine (ATC, AVX754) by against HIV and hepatitis B in analog reverse transcriptase inhibitors Avexa. A meeting with the FDA in early laboratory studies. In a Phase I/II (NNRTIs or non-nukes) 2011 discussed results from Phase study, Racivir showed anti HIV activity  Fact sheet 440: protease inhibitors II/III studies. Avexa is proceeding with that lasted more than 2 weeks after the  Fact sheet 460: attachment and its development. drug was stopped. The makers hope fusion inhibitors that Racivir can be used as a once-  Fact sheet 470: new classes of CMX157 by Chimerix is a version of daily drug. antiviral drugs tenofovir with better properties in the  Fact sheet 480: immune therapies body. It has completed a Phase I trial.</p><p>These drugs have not been Dexelvucitabine (DFC), formerly approved by the Food and Drug known as Reverset, is being developed Administration (FDA) for use by Pharmasset. DFC is taken as a pill, NUKES NO LONGER IN against HIV. once a day. It has shown activity DEVELOPMENT against HIV with resistance to various The following drugs are no longer antiretroviral drugs. being developed for use against HIV:</p><p>NUCLEOSIDE ANALOG DOT (Dioxolane thymidine) is being  Adefovir dipivoxil (bis POM REVERSE TRANSCRIPTASE studied by the University of Georgia in PMEA) by Gilead Sciences Phase I trials.  Alovudine (MIV-310, FLT) by INHIBITORS Boehringer Ingelheim and Medivir These drugs stop HIV from multiplying Elvucitabine (ACH-126,443, Fd4C) by  DAPD (amdoxovir) by RFS by blocking the reverse transcriptase Achillion Pharmaceuticals is a once- Pharm was discontinued in 2010 enzyme. This enzyme changes HIV’s daily drug with activity against HIV that  dOTC (BCH-10652, BCH-10618) genetic material (RNA) into the form of is resistant to several other nukes. It is by BioChem Pharma DNA. This step has to occur before also effective against hepatitis B. It HIV’s genetic code gets combined with  FddA (Beta-fluoro-ddA, has successfully completed one year of an infected cell’s own genetic codes. Lodenosine) by US Bioscience a Phase II study. The nucleoside analogs (often called  GW420867X by GlaxoSmithKline “nukes”) mimic the building blocks  Lobucavir by Bristol-Myers Squibb Festinavir (E-d4T, OBP-601) by used by reverse transcriptase to make  SPD756 by Shire Pharmaceuticals Bristol-Myers Squibb showed good copies of the HIV genetic material. results in a Phase I trial. It may be a These fake building blocks disrupt the once-daily drug. copying. 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. </p><p>MIV-210 (FLG) by GlaxoSmithKline and Medivir shows good activity against HIV with resistance to other nukes. It is in Phase I trials. A Project of the New Mexico AIDS Education and Training Center. Partially funded by the National Library of Medicine Fact Sheets can be downloaded from the Internet at http://www.aidsinfonet.org Revised April 4, 2011</p><p>A Project of the New Mexico AIDS Education and Training Center. Partially funded by the National Library of Medicine Fact Sheets can be downloaded from the Internet at http://www.aidsinfonet.org</p>