TreatmentUpdate40: February 1993
Sean Hosein
Researchers in the USA have been conducting a series of experiments on humans with HIV infection and various doses of d4T given orally or intravenously. When taken orally 80% of d4T is absorbed. The drug can also penetrate into the CSF (cerebrospinal fluid; in which the brain and spinal cord float). When given orally, blood levels of d4T have often been higher than would be needed for suppression of viral activity. It should be noted, however, that d4T blocks production of viruses only inside infected cells. Thus, it is the concentration of d4T inside the cell (the intracellular concentration) that is important, not blood levels of the drug. Once inside a cell, d4T must first be converted to its anti-viral form. Only in its anti-viral state (called the triphosphate) can d4T block viral replication. Once the drug has been processed into its anti-viral form, the intracellular concentration of the drug slowly declines. As a result of this slow decline, it is thought that d4T need only be taken twice daily.
Meanwhile, researchers with the National Toxicology Program in the USA have been investigating the toxicity of several anti-HIV agents including d4T. Mice given high doses (250 mg/kg/day) of the drug for 22 days developed bone marrow toxicity. In tests of immune function, d4T did not appear to reduce the number of T-cells. These tests do not provide data on (1) the long-term risks of using d4T, (2) the ability of the drug to cause mutations and/or tumours, nor do they provide (3) a clear account of the interaction between d4T and the immune system.
1. Dudley MN, Graham KK, Kaul S, et al. Pharmacokinetics of stavudine in patients with AIDS or AIDS-related complex. Journal of Infectious Diseases 1992;166:480-485.
2. Luster MJ, Rosenthal GJ, Cao W, et al. Experimental studies of the hematologic and immune system toxicity of nucleoside derivatives used against HIV infection. International Journal of Immunopharmacology 1991;13 (supplement 1):99-107.
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