NEW YORK (Reuters Health) - Although multidrug-resistant HIV strains, because they are potentially less virally fit than non-drug resistant strains, were hoped to be less likely to cause disease, a report published this month suggests just the opposite.
After transmission of a resistant HIV strain, the virus is able to evolve to become more fit and cause significant disease, according to the study in the December 15th issue of Clinical Infectious Diseases.
“The frequency of HIV that is resistant to current medications seems to be growing, and this may limit global treatment strategies,” Dr. Rajesh T. Gandhi from Partners AIDS Research Center in Boston, who led the study, noted in comments to Reuters Health.
Dr. Gandhi and colleagues monitored viral evolution after transmission of HIV-1 containing multiple reverse transcriptase (RT) and protease mutations (PR) in a 32-year-old previously healthy man.
In the absence of ongoing antiretroviral therapy, 5 of 12 drug resistance mutations reverted in a stepwise fashion to wild type over the course of one year. Of note, reversal of the M184V mutation alone did not produce a change in replicative capacity but it did enhance resistance to zidovudine and tenofovir.
However, “reversions of a second (RT) mutation and 3 PR mutations were associated with an increase in viral replicative capacity and this was temporally correlated with a marked decrease in CD4 cell number,” the researchers report.
Dr. Gandhi and colleagues say this study “demonstrates the gradual stepwise back-mutation of certain drug resistance mutations in vivo in the absence of ongoing drug selection pressure.”
While larger studies are needed to confirm these findings, Dr. Gandhi told Reuters Health, this report “emphasizes that the recent increase in HIV transmission among men who have sex with men in the United States may result in acquisition of multidrug resistant virus, with very serious consequences.”
Source: Clin Infect Dis 2003;37:1693-1698. [ Google search on this article ]
MeSH Headings:Retroviridae Proteins: Viral Core Proteins: Viral Proteins: Viral Structural Proteins: Gene Products, pol: Drug Resistance, Multiple: HIV-1 Reverse Transcriptase: Nucleocapsid Proteins: PolyproteinsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
