The view that d4T/ddI can be used after AZT-based combinations has been called into question once more by data from a French study of AZT/ddC-experienced individuals. It confirms a 1998 report from the ALTIS 2 study that virological response to d4T is blunted if HIVis already resistant to AZT.
Twenty people with an average of 11 months AZT/ddC experience (range 7-42 months) were switched to d4T/ddI. 65% had detectable NRTI resistance. In all but one case the resiatance pattern included the T215Y mutation, with accompanying changes at codons 41 or 210. One individual had developed multi-nucleoside resistance with a mutation at codon Q151M.
Those with resistance had a much poorer viral load response after three or six months on d4T/ddI (-0.5log and -0.1 log versus 1.6 log and 2 log in those without resistance). None of those with AZT or multinucleoside resistance had viral load below 1,000 copies after six months, whereas 50% of those without resistance had reached this level.
The researchers conclude that resistance testing when switching therapy "deserves maximal attention".
Reference
Izopet J et al. Mutations conferring resistance to zidovudine diminish the anti-viral effect of stavudine plus didanosine. Journal of Medical Virology 59 (4): 507-511, 1999.