As with all other anti-HIV drugs, strains of HIV that are resistant to ddI (didanosine, Videx / VidexEC) may emerge after a period of treatment. The emergence of drug-resistant strains coincides with a fall in the effectiveness of the drug. If blood levels of the drug fall too low, this will help the development of resistance to ddI and may affect future treatment options.

The development of ddI-resistant strains of HIV has been seen after some months taking the drug, although it appears to be much less common than resistance to AZT (zidovudine, Retrovir) or 3TC (lamivudine, Epivir).

The commonest resistance mutations that develop with ddI treatment include K65R, L74V, V75T/M/A and Q151M^[1]. There is also some evidence that the mutations that reduce ddI’s effectiveness only occur when the virus is also resistant to AZT, and that AZT can block the development of ddI resistance^[2].

Resistance to ddI is unlikely to cause cross-resistance to AZT or to d4T (stavudine, Zerit). In fact, ddI may prevent the development of AZT resistance when the two drugs are combined^[3]. ddI is also active against virus that is resistant to 3TC, so it may also be a useful drug in second-line therapy after the development of 3TC resistance.

There is some evidence that people with HIV strains that have become resistant to AZT may regain sensitivity to AZT after treatment with ddI^[4]. However, it is also clear that strains of virus resistant to both AZT and ddI can develop.