There are 3 new topical treatments for herpes labialis that have either been approved by the US Food and Drug Administration (penciclovir cream [Denavir] and n-docosanol cream [Abreva]) or recently undergone extensive clinical evaluation (acyclovir cream). of Medicine, Johns Hopkins University School of Medicine, 1830 Monument St., Baltimore MD 21205. Emergence of acyclovir resistance during clinical use appears to parallel the in vitro observations of selection for TK-deficient, acyclovir-resistant viruses following serial passage in the presence of the drug. In contrast to immunocompetent patients, the combination of prolonged antiviral prophylaxis or treatment and impaired immune response can lead to the development of ACV resistance, which has been reported in up to 27% of allogeneic HCT recipients; lower levels have been reported in patients with HIV or hematologic malignancies, whereas resistance is very infrequent in immunocompetent patients 4, 5 and 6. Considering their interaction, recent studies showing that acyclovir treatment could reduce HIV viral load in co-infected patients were not surprising, and attributed to an indirect effect of HSV suppression. However, Moira McMahon and colleagues at Johns Hopkins decided to look whether the effects on HIV might be direct. In this report, we use a single round HIV infectivity assay to show that acyclovir directly inhibits HIV infection with an IC50 of ∼5 μm.
The drug specifically targeted RT, the key HIV enzyme that converts the virus’ RNA into DNA so it can be replicated. All patients received antiviral prophylaxis with oral ACV 400 mg by mouth twice daily for at least 100 days after transplantation. The V75I strain is part of the resistance pathway to many drugs, including the commonly used RT inhibitors. What this means, the authors note, is that acyclovir could be a great model for designing future HIV treatments, but also could be a risky drug if given to HSV patients co-infected with HIV by potentially promoting cross-resistance to current treatments. ↵* This work was supported, in whole or in part, by National Institutes of Health Grants AI43222 (to R. Disclaimer: AAAS and EurekAlert! Given the severity and persistence of disease, combined therapy was then attempted despite the fact that she had worsened while on foscarnet in the past: high-dose continuous infusion ACV of 30 mg/kg/day plus daily foscarnet was administered with eventual complete resolution of herpetic lesions.
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