It’s been over 60 years since human immunodeficiency virus (HIV) was first detected and about 40 years since acquired immunodeficiency syndrome (AIDS) was recognized as a new disease. Yet we still don’t have a cure. Thankfully, dozens of medications have been developed to treat HIV type-1 (HIV-1) improving the long term survival for individuals living with the disease. The first HIV antiretroviral drug approved by the U.S. Food and Drug Administation (FDA) in 1987 was a nucleoside reverse transcriptase inhibitor (NRTI) called zidovudine. Let’s take a look at this drug and examine how it works.

HIV Life Cycle (National Instute of Health, 2023)

Also known as azidothymidine, ZDV, Retrovir, and formerly AZT, zidovudine is approved to treat HIV-1 infection and to prevent perinatal HIV-1 transmission from a pregnant individual to their newborn infant. The drug is no longer used as monotherapy, but works most effectively when combined with other antiretroviral agents.
 
To understand the mechanism behind zidovudine, we should first review the HIV life cycle. When HIV enters the body, it attacks CD4, the white blood cells that fight infection.

1. HIV first binds to receptors on the surface of a CD4 host cell.
2. The HIV and CD4 fuse together, permitting the HIV to enter the CD4 cell.
3. Once inside the CD4 cell, HIV releases and uses the enzyme reverse transcriptase to convert its genetic material HIV ribonucleic acid (RNA) into HIV deoxyribonucleic acid (DNA). This process allows HIV to enter the CD4 nucleus.
4. Inside the CD4 nucleus, HIV releases the enzyme integrase to insert its DNA into the CD4 cell DNA, taking over the host genetic mechanism.
5. HIV can then use its messenger RNA and the CD4 host cell to create long chains of HIV proteins, the building blocks for the virus.
6. New HIV proteins move to the surface of the cell and create immature (noninfectious) HIV.
7. New immature HIV pushes itself out of the host CD4 cell, releases the enzyme protease which breaks up the long protein chains, and creates mature or infectious virus.

How Does Zidovudine Work?

Zidovudine is a synthetic molecule that mimics the structure of reverse transcriptase. It works by integrating into new viral DNA and inhibiting HIV-1 reverse transcriptase from converting RNA to DNA. This blocks the replication process and disrupts the HIV-1 life cycle.

Nursing Considerations

• Originally developed in oral and intravenous (IV) formulations, oral is the preferred route for zidovudine.
• It is no longer a first-line agent or used as monotherapy. Zidovudine is administered in combination with other antiretroviral agents (National Institute for Health, 2023):
  • Abacavir, lamivudine and zidovudine (Trizivir)
  • Lamivudine and zidovuding (Combivir)
• Zidovudine is contraindicated in patients who experience severe life-threatening allergic reaction to any component of the medication. It is also contraindicated in patients with Stevens-Johnson syndrome.
• Monitor patients closely for side effects including nausea, vomiting, diarrhea, headache, myalgias, insomnia, bone marrow suppression, peripheral myopathy, lactic acidosis, elevated liver enzymes, and hepatotoxicity (Edwards, Ingold & Azmat, 2023).
  • Administration with food may alleviate gastrointestinal symptoms.
• Routinely monitor laboratory tests (Facts and Comparisons, 2023):
  • Complete blood count (CBC) with differential; assess for signs of hematologic toxicity, bone marrow suppression, neutropenia, leukopenia, and anemia.
  • Liver function tests (LFTs); zidovudine has been associated with severe hepatomegaly with steatosis.
  • Serum creatinine; assess for signs of renal impairment; dose may need adjustment.
  • HIV viral load
  • CD4 count

Regardless of the antiretroviral regimen selected, patient education is of utmost importance. Emphasize that compliance with treatment will improve the patient’s quality of life, reduce the risk for infections or neoplasms and prolong their overall survival (Edwards, Ingold & Azmat, 2023).
 
For complete information, please consult the drug’s specific package insert or the Nursing2024 Drug Handbook® + Drug Updates.
 

References
 
Edwards, Z., Ingold, C.J., & Azmat, C.E. (2023, February 11). Zidovudine. StatPearls [Internet] https://www.ncbi.nlm.nih.gov/books/NBK554419/
 
Facts and Comparisons (2023, July 31). Zidovudine Oral. Facts and Comparisons. https://fco.factsandcomparisons.com/lco/action/doc/retrieve/docid/fc_dfc/5549800
 
National Institute for Health. (2023, March 23). FDA-Approved HIV Medicines. https://hivinfo.nih.gov/understanding-hiv/fact-sheets/fda-approved-hiv-medicines.