Reduction of the IC50 of ddI by Hydroxyurea (HU)
against HIV
(ICAAC abstract I-124, authors: KZ Rana et al)
At ICAAC, investigators reported the results of an in vitro study showing that HU reduced the amount of ddI needed to reach the IC50. The IC50 is the inhibitory concentration of a drug needed to inhibit 50% of virus replication. It is a standard method used by researchers.
The authors stated, "It appears that less ddI when used in combination with HU is needed to obtain a similar antiretroviral effect when given alone...[T]he increase in activity observed was most likely due to the increase in the active component of ddi (ddATP) without a concomitant increase in the host (dATP)....Therefore, the ratio between these two components grew larger and more ddATP could be available to compete (with dATP) and inhibit reverse transcriptase or to become incorporated into elongating HIV DNA chains."
This information opens the possibility that less ddI than the standard dose of 200 mg bid (400 mg daily) could be used for those with ddI intolerance when used in combination with HU. Further studies are necessary to explore this possibility.