AZT 5’-Phosphonates: Achievements and Trends in the Treatment and Prevention of HIV Infection

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Abstract


Despite the numerous drawbacks, 3’-azido-3’-deoxythymidine (AZT, Zidovudine, Retrovir) remains one of the key drugs used in the treatment and prevention of HIV infection in both monotherapy and HAART. A strategy in searching for new effective and safe AZT agents among latent (depot) forms of AZT has yielded its first positive results. In particular, the sodium salt of AZT 5’-H-phosphonate (Nikavir, phosphazide) has demonstrated clinical advantages over parent AZT: first and foremost, lower toxicity and better tolerability. It can be effectively used for the prevention of vertical transmission from mothers to babies and as an alternative drug for HIV-infected patients with low tolerance to Zidovudine. Preclinical studies of another phosphonate, AZT 5’-aminocarbonylphosphonate, have demonstrated that it releases AZT when taken orally. Pharmacokinetic studies have shown a prolonged action potential. Based on the analysis of both toxicological and pharmacological data, AZT 5’-aminocarbonylphosphonate has been recommended for clinical trials.


А. L. Khandazhinskaya

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Author for correspondence.
Email: khandazhinskaya@bk.ru

Russian Federation

E. A. Shirokova

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: khandazhinskaya@bk.ru

Russian Federation

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