Levels of didanosine (ddI) can be boosted with a cheap drug used to prevent gout, according to researchers from Belgium, reporting in the November 19 issue of AIDS (now available online). They suggest that clinical trials should be set up to investigate whether boosting ddI levels with allopurinol would permit standard ddI doses to be halved in resource-limited settings. They also emphasise the need to determine whether this strategy is safe before it is adopted in clinical practice.
Allopurinol is an inhibitor of xanthine oxidase and has been shown to increase ddI levels when administered prior to ddI treatment. The boosting effect is believed to occur during the first-pass metabolism of ddI in the gut and the liver.
The researchers recruited four treatment-naïve patients already receiving treatment with ddI, hydroxyurea and chloroquine. All had viral load below 400 copies/ml, when they agreed to reduce their ddI dose from 400mg a day to 200mg a day. Plasma levels of ddI were measured before and after the dose reduction.
No significant reduction in plasma didanosine levels occurred either one month or four months after the ddI dose reduction, and no changes in viral load were observed.
Allopurinol was dosed at 300mg a day; at current prices this would cost approximately 75 pence ($1 US) a month. The researchers suggest that future use of ddI and allopurinol might be explored in combination with 3TC and either nevirapine or efavirenz, to allow the assembly of a convenient once-daily combination. However they also warn that the risk of hypersensitivity reaction to allopurinol (characterised by skin rash affecting 1-3% of individuals in the first year of treatment) is unknown in individuals with HIV infection.
Boelaert JR et al. The boosting of didanosine by allopurinol permits a halving of the didanosine dosage (Research letter). AIDS 16 (16): 2221-23, 2002.