Re: re: In response to Nicholas Bennett 26 August 2004
Previous Rapid Response Next Rapid Response Top
Nicholas Bennett,
Infectious Disease Postdoc/Clinician
Department of Pediatrics, University Hospital, Syracuse NY

Send response to journal:
Re: Re: re: In response to Nicholas Bennett

Dear Pennee,

I could not recreate your experience with Viracept and Herpes. The only mentions I found were in the context of "antiviral medications" where Viracept was listed as anti-HIV and others like Aciclovir were listed for Herpes.

Viracept is a protease inhibitor, and since herpes doesn't rely on a protease in the same way as HIV it can't be expected to have an effect.

She is however quite right about the off-patent use of drugs (and the financial restrictions on drug development and use, sadly enough). Some are used as per "common sense", others in people for whom the license was not originally intended. Sadly the risks of litigation are all too real in medicine: malpractise insurance in parts of the US can easily reach 70,000 dollars per annum, a significant cut from one's salary! If junior doctors were to make such decisions on their own they would quite quickly find that their seniors would come down like a ton of bricks - ultimately the responsibility could rest with them!

She is also right that antivirals do not go into their own seperate baskets - well, half-right anyway. This is why they are put into classes like protease inhibitors, TK inhibitors, RT inhibitors, neuraminidase inhibitors etc etc. As for why there are sometimes several types of the same drug:

1 - A new drug may have a better side effect profile.

2 - A new drug may be cheaper (very unlikely!).

3 - A new drug may have better effects.

4 - A new drug may have a better formulation (injection versus pill say)

5 - A new drug may beat a resistance profile (e.g. penicillin versus methicillin)

As for why the tests do not change, the answer is that they do. There are several reports in the literature of new strains of HIV being discovered that require updates to the tests (Group O was the last big change). But the simple fact is that in a 10,000 base genome some bits need to stay the same. Otherwise the virus wouldn't be HIV! It is the conserved bits that are targetted by antivirals and by the tests. Sadly biology dictates that there will be a pressure to find ways around these conserved areas. This is where antiviral resistance occurs, and because the drugs are of certain classes sometimes resistance to one drug means that several others are also rendered useless, just as Pennee suggests.

There is indeed known genetic mutations that are linked to certain drugs: you can reliably predict how a virus will respond to therapy based on what the sequence of the virus is, so-called genotypic testing. In this way you can avoid using drugs that won't work with that particular virus.

AZT was indeed developed as an anticancer drug, but it was rejected as non-toxic as I have pointed out here before. Richard Beltz has been often mis-quoted as saying it was too toxic, a quote he denies. It is however finding some positive effects in combination with other drugs, through it's effects on the reverse transcriptase component of the telomerase complex. Again, a reverse-transcriptase inhibition, no different from in HIV or Hepatitis B - it makes perfect sense.

The lack of triphosphorylation reference is from the Perth Group, and I'm inclined to reject that out of hand for the following simple reason: if you put AZT into a virus culture it prevents replication unless resistance mutations exist in the virus. Clearly it MUST be active...

Competing interests: None declared