Hiv-1 型抗药性也许随时间而减小
WESTPORT, CT (Reuters Health) - Certain drug-resistant HIV-1 variants appear less able to replicate than their wild-type counterparts, a finding that might eventually allow effective reintroduction of "failed" medication, according to UK researchers.
In the October issue of the Journal of Medical Virology, Dr. Helen L. Devereux of the Royal Free and University College Medical School in London and colleagues note that it may be that "viruses containing mutations associated with drug resistance are less fit than the wild-type." In the absence of therapy, this hypothesis holds, wild-type viruses prevail.
To investigate, the researchers studied 11 HIV-1-infected men who had developed resistance to many antiretroviral drugs and had taken a break from therapy. These subjects were assessed for drug-resistant mutations in the protease (PR) and reverse transcriptase (RT) genes before and repeatedly after stopping therapy. The rate of disappearance of mutant viruses when therapy ended was used as a measure of relative viral fitness.
The researchers found that "certain primary mutations in PR and RT present in patients taking highly active antiretroviral therapy were associated with a substantial reduction in the viral fitness." Other mutations in the PR gene remained "fairly constant" and "may not significantly reduce viral fitness."
This "rapid repopulation of wild-type virus in patients with high-level resistance to multiple drugs has some intriguing therapeutic implications," say the investigators. At some point after the withdrawal of a particular drug, they add, "the resistant virus population may be reduced to low enough levels to re-introduce that drug as part of a new potent regimen.", 百拇医药
In the October issue of the Journal of Medical Virology, Dr. Helen L. Devereux of the Royal Free and University College Medical School in London and colleagues note that it may be that "viruses containing mutations associated with drug resistance are less fit than the wild-type." In the absence of therapy, this hypothesis holds, wild-type viruses prevail.
To investigate, the researchers studied 11 HIV-1-infected men who had developed resistance to many antiretroviral drugs and had taken a break from therapy. These subjects were assessed for drug-resistant mutations in the protease (PR) and reverse transcriptase (RT) genes before and repeatedly after stopping therapy. The rate of disappearance of mutant viruses when therapy ended was used as a measure of relative viral fitness.
The researchers found that "certain primary mutations in PR and RT present in patients taking highly active antiretroviral therapy were associated with a substantial reduction in the viral fitness." Other mutations in the PR gene remained "fairly constant" and "may not significantly reduce viral fitness."
This "rapid repopulation of wild-type virus in patients with high-level resistance to multiple drugs has some intriguing therapeutic implications," say the investigators. At some point after the withdrawal of a particular drug, they add, "the resistant virus population may be reduced to low enough levels to re-introduce that drug as part of a new potent regimen.", 百拇医药