Common AZT mutations weaken d4T/ddI response

Keith Alcorn
Estimated reading time 1 minutes
This article is more than 24 years old.

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.

Glossary

log

Short for logarithm, a scale of measurement often used when describing viral load. A one log change is a ten-fold change, such as from 100 to 10. A two-log change is a one hundred-fold change, such as from 1,000 to 10.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

codon

A position within a gene.

resistance testing

Laboratory testing to determine if an individual’s HIV strain is resistant to anti-HIV drugs. 

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

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.

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