NEW YORK (Reuters Health) - Patients carrying a particular mutation in the reverse transcriptase region of the HIV-1 pol gene face an increased risk of virologic failure on regimens that include thymidine analogs, according to a report in the January 23rd issue of AIDS.
The presence of T215Y/F mutations in the reverse transcriptase region of HIV-1 pol gene confers a high resistance to thymidine analogs, the authors explain, but the effect of 215 revertants - intermediates on the pathway of reversion from 215Y/F to wild-type 215T viruses - is not known.
Dr. Claudia Balotta from University of Milan, Italy and colleagues evaluated the effect of HIV-1 215 variants on the virological outcome of therapy in 491 patients beginning a thymidine analog-containing highly active antiretroviral therapy (HAART) regimen.
Just over 3% of patients with recent or chronic HIV-1 infection had HIV-1 215 revertants, the authors report, whereas nucleoside-associated mutations were significantly more common in recently infected (15.8%) or chronically infected (6.8%) patients.
By week 52, 47% of patients carrying 215 revertants experienced virological failure, the results indicate, compared with 30% of patients who did not carry such mutations.
In multivariable analysis, the adjusted hazard of virological failure was three times higher in patients with 215 revertants than in patients without such mutations, the researchers note.
Even after adjusting for the number of other reverse transcriptase mutations, the presence of 215 revertants before therapy initiation increased the risk of detecting a 215Y/F mutation at virological failure by more than 30-fold, the report indicates.
“Our data provide evidence that the so-called 215 revertants are associated with an increased risk of virological failure at week 24 of HAART regimens containing zidovudine or stavudine,” Dr. Balotta told Reuters Health. “Moreover, they are also associated with the emergence of one of the major mutations (the 215Y/F) associated with resistance to nucleoside analogs.”
“Full adherence to therapy is critical for patients carrying 215 revertants, because a thymidine analogs-sparing regimen may be the only one effective for patients carrying these mutations,” Dr. Balotta said. “Close monitoring of virological and immunological parameters is crucial to evaluate the effects of therapy.”
“At present, we know little about the transmission efficiency and replicative capacity of resistant strains,” Dr. Balotta concluded. “Insights on this matter may help in exploiting mechanisms of resistance and treating subjects with resistant strains.”
Source: AIDS 2004;18:227-235. [ Google search on this article ]
MeSH Headings:Pyrimidine Nucleotides: Thymine Nucleotides: Genes, polCopyright © 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.
