skip navigation

Skip Nav

AIDSinfo Drug Database

AIDSinfo Drug Database

Drugs by class



Amdoxovir  Audio icon

Other Names: AMDX, DAPD, prodrug of DXG
Drug Class: Nucleoside Reverse Transcriptase Inhibitors
Molecular Formula: C9 H12 N6 O3
Registry Number: 145514-04-1 (CAS)
Chemical Name: [(2R,4R)-4-(2,6-diaminopurin-9-yl)-1,3-dioxolan-2-yl]methanol
Chemical Class: Purine Nucleosides
Company: Biochem Pharma; Triangle Pharmaceuticals; Gilead Sciences; RFS Pharma
Phase of Development: Phase II
Chemical Image:
Click image to enlarge
Molecular Weight: 252.233
(Compound details obtained from ChemIDplus Advanced1 and NIAID Therapeutics Database2)

What is an investigational drug?

An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.

What is amdoxovir?

Amdoxovir is an investigational drug that is being studied for the treatment of HIV infection.

Amdoxovir belongs to a class (group) of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs).2 NRTIs block an HIV enzyme called reverse transcriptase. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) By blocking reverse transcriptase, NRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body.

Amdoxovir is a prodrug, which means that it is an inactive drug. Once taken, a prodrug does not work until the body converts it into an active form. In the body, amdoxovir is converted to DXG-TP.3

In vitro studies have shown that amdoxovir may be an effective option for treating people for whom the NRTIs lamivudine, emtricitabine, zidovudine, and stavudine are not working. However, it is possible for someone to develop drug resistance to amdoxovir and for amdoxovir to then not work in that person.4,5

In vitro studies have also shown that amdoxovir is active against hepatitis B virus (HBV).3

How are clinical trials of investigational drugs conducted?

Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.6

  • Phase I trials: Researchers test an investigational drug in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
  • Phase II trials: The investigational drug is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
  • Phase III trials: The investigational drug is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the investigational drug to be used safely.6
In most cases, an investigational drug must be proven safe and effective in a Phase III clinical trial to be considered for approval by the FDA for sale in the United States. Some drugs go through the FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by the FDA and made available to the public, researchers track its safety in Phase IV trials to seek more information about the drug’s risks, benefits, and optimal use.6

In what phase of testing is amdoxovir?

Amdoxovir is currently being studied in Phase II clinical trials.2

What have recent studies shown about amdoxovir?

A Phase I/II study looked at the effectiveness of three different treatments in HIV-infected adults: twice-daily amdoxovir monotherapy, amdoxovir given in combination with a standard dose of the HIV medicine zidovudine (brand name: Retrovir), and amdoxovir given in combination with a reduced dose of zidovudine. Some of the study participants had never taken HIV medicines before entering the study (treatment-naive), and others had taken HIV medicines previously (treatment-experienced). The treatment-experienced participants were required to be off HIV medicines for at least 3 months before starting the study. Each of the three treatment groups was compared to a group of participants taking a placebo. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.) 5,7 

In this study, amdoxovir given in combination with either a standard dose or a reduced dose of zidovudine proved similarly effective in reducing HIV in the blood (viral load). Also, amdoxovir combined with the reduced dose of zidovudine was significantly more effective in reducing viral load than amdoxovir alone, suggesting a potentially beneficial drug synergism. (In this case, drug synergism of amdoxovir and zidovudine is when the drugs work well together, resulting in a greater decrease in viral load than amdoxovir alone.) However, longer studies will need to be undertaken to confirm thes findings. In terms of safety, both amdoxovir and amdoxovir in combination with zidovudine appeared to be safe. Side effects were reported as being temporary and mild to moderate. No participants stopped the study because of abnormal laboratory values or adverse events.7

A Phase II study of treatment-experienced adults who have HIV that is prone to not being affected by NRTIs is currently being planned. This study will compare twice-daily amdoxovir to once-daily tenofovir disoproxil fumarate (brand name: Viread). Both amdoxovir and tenofovir disoproxil fumarate will be studied in combination with zidovudine plus a third drug. (The third drug will initially be an HIV medicine that is not working for the participant, and then it will be switched to the HIV medicines lopinavir and ritonavir after the 2nd week of the study.)8

What side effects might amdoxovir cause?

In the Phase I/II study discussed under the previous question, amdoxovir alone and amdoxovir in combination with zidovudine appeared to be safe. Side effects were reported as being temporary and mild to moderate. The most common side effects reported among the group receiving amdoxovir combined with zidovudine were headache and nausea.7

Because amdoxovir is still being studied, information on possible side effects of the drug is not complete. As testing of amdoxovir continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying amdoxovir?

More information about amdoxovir-related research studies is available from the AIDSinfo database of study summaries. Click on the title of any trial in the list to see the trial summary and more information about the study.

I am interested in participating in a clinical trial of amdoxovir. How can I find more information about participating in a clinical trial?

Participating in a clinical trial can provide benefits. For example, a volunteer participant can benefit from new research treatments before they are widely available. Participants also receive regular and careful medical attention from a research team that includes doctors and other health professionals. However, clinical trials may also involve risks of varying degrees, such as unpleasant, serious, or even life-threatening side effects from the treatment being studied.6

Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.


1. United States National Library of Medicine. ChemIDplus Advanced.

2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development.

3. Hurwitz SJ, Asif G, Fromentin E, Tharnish PM, Schinazi RF. Lack of Pharmacokinetic Interaction between Amdoxovir and Reduced- and Standard-Dose Zidovudine in HIV-1-Infected Individuals. Antimicrob Agents Chemother. 2010 Mar;54(3):1248-55.

4. Pozniak AL. Investigational agents for salvage. Curr Opin HIV AIDS. 2009 Nov;4(6):524-30.

5. Murphy RL, Kivel NM, Zala C, et al. Antiviral activity and tolerability of amdoxovir with zidovudine in a randomized double-blind placebo-controlled study in HIV-1-infected individuals. Antivir Ther. 2010;15(2):185-92.

6. National Institutes of Health (NIH). NIH Clinical Research Trials and You.

7. Murphy R, Zala C, Ochoa C, et al. Pharmacokinetics and Potent Anti-HIV-1 Activity of Amdoxovir Plus Zidovudine in a Randomized Double-blind Placebo-controlled Study. Poster presented at: 15th Conference on Retroviruses and Opportunistic Infections (CROI); February 3-6, 2008; Boston, MA. Poster 794.

8. RFS Pharma, LLC. A Phase IIa, Randomized, Double-blind, Active-controlled, 12-week Study of Amdoxovir (Two Doses) Versus Tenofovir DF, in Combination With Zidovudine in HIV-1 Treatment-experienced Subjects With M184I/V Mutation in Addition to 0-2 Confirmed Thymidine Analog Mutations. In: Bethesda (MD): National Library of Medicine (US). Registered on November 27, 2012. NLM Identifier: NCT01737359. Last accessed April 26, 2013.

Last Reviewed: May 29, 2013

Last Updated: May 29, 2013

Back to Top