Viral Resistance to Acyclovir

[Guest guest]

This article, forwarded by DAN! doctor Geoff Radoff MD whose offices

are in Arizona and Santa , sheds some light on the possibility

that Acyclovir may cause viral mutation and resistance in a subset

of folks.

Could it be due to the fact the virus can migrate to areas that

acyclovir can not travel, like beyond the blood brain barrier? Or

that that acyclovir does not get to the liver as well as the

conversion of acyclovir from Valtrex (which happens in the liver)?

We don't truly know, but it, IMO, raises another question about the

use of trying acyclovir prior to trying Valtrex.

- Stan

http://www.pubmedcentral.gov/articlerender.fcgi?artid=180320

Drug resistance patterns of herpes simplex virus isolates from

patients treated with acyclovir.

C McLaren, M S Chen, I Ghazzouli, R Saral, and W H Burns

This article has been cited by other articles in PMC.

Abstract

A decrease in the in vitro sensitivity to acyclovir (ACV) was

observed in successive isolates of herpes simplex virus type 1 from

three immunocompromised patients during intravenous therapy with

this drug. The ACV-resistant isolate from patient 1 was cross-

resistant to dihydroxypropoxymethylguanine and

bromovinyldeoxyuridine, but still susceptible to three fluoro-

substituted pyrimidines, 2'-fluoro-5-iodo-1-beta-D-

arabinofuranosylcytosine (FIAC), 2'-fluoro-5-iodo-1-beta-D-

arabinofuranosyluracil (FIAU), and 2'-fluoro-5-iodo-1-beta-D-

arabinofuranosylthymine (FMAU). The thymidine kinase (TK) from the

resistant isolate showed a 50-fold or greater reduction in affinity

for thymidine, FIAU, FMAU, and ACV, but the total enzyme activity

was similar to that of the sensitive isolate. The ACV-resistant

isolate from patient 2 was also resistant to

dihydroxypropoxymethylguanine, bromovinyldeoxyuridine, and the

fluoro-substituted compounds; TK activity for this isolate was less

than 1% of the patient's pretherapy isolate. An isolate obtained

during a subsequent recurrence in patient 2 was susceptible to ACV

and the other TK-dependent agents. The ACV-resistant isolate from

patient 3 was partially resistant to FIAC and FIAU but still

susceptible to FMAU; the viral TK had a 10-fold-lower affinity for

ACV, FIAU, and FMAU than did the sensitive pretherapy isolate, while

the level of TK activity detected was reduced to 6%. In none of the

isolates studied was a change in sensitivity to phosphonoformic acid

observed. Compared with the corresponding pretherapy ACV-sensitive

isolates, there was a 30-fold decrease in neurovirulence for mice of

the two drug-resistant isolates with diminished levels of thymidine-

phosphorylating activity and no change in virulence for the third

isolate. These findings indicate that mixed patterns of drug-

resistance to TK-dependent antiviral compounds can occur in clinical

isolates, resulting from changes in either the amount or the

affinity of viral TK activity.