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AZT and cross-resistance with d4t

Mar 3, 2002

In your response to a question on AZT monotherapy you stated that resistance to AZT causes cross-resistance with d4t. I was using only AZT in 1996-7 and had a failure. V/L went from 200,000 to 710 and back up to 14,000 for about six months until I started HAART; first using ritonovir, d4t, and 3TC, about two years ago switched the ritonovir for nevirapine. My V/L has been undetectable since Dec. 1997. Your response to the previous question suggests that I, too, have resistance to d4t and am therefore relying on just the other two drugs for viral suppression. Do you think this is correct? Am I risking a treatment failure with this combo? Should I change the d4t for something else? If so what? or am I just obsessing too much? Thanks for your help

Response from Dr. Young

Thank you for your question and astute assessment of your treatments.

There is a high degree of cross resistance between the two thymidine analogues (AZT and d4T); the fact that you had rebound in your viral load suggests to me that you might have at least some degree of resistance.

The key thing to note, however, is that resistance is not all or nothing-- that is to say that even when there is some resistance, this does not mean that there is no antiviral effect of medication.

Nevertheless, one can safely conclude that the potentcy of the d4T in your current regimen of d4T/3TC/nevirapine has been compromised to some degree. The fact that your viral load remains undetectable is very reassuring; in my practice, I typically don't switch persons off of sucessful, well tolerated regimens.

Recent data, though has placed a grey cloud over stavudine use (see several reports from this year's Retrovirus Conference-- e.g., Carr, Kumar, Longeran)-- reports that note slight increases in total cholesterol, triglycerides, risk of adverse reactions; Carr's report suggests improvments in lipodystrophy when persons are switched off of d4T. In total, suggesting that if I had a reason to consider a switch, it might be reasonable. This is not to say that persons who are doing well, have no risk of resistance or low risk of other complications should necessarily be switched off d4T.

The question, then if you are contemplating a switch, is what to switch to-- clearly not AZT; the nucleoside/nucleotide options are ddI (may need to take separtely from your other medications and some risk of neuropathy); abacavir (risk of allergic reaction, possible compromise of potentcy with AZT resistance)or tenofovir. I'd discuss these options with your health care provider.

Hope this is helpful, BY

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