SAN FRANCISCO (Reuters Health) - Drug-resistant HIV variants may persist in untreated individuals with primary HIV infection for more than 3 years, according to a report presented here at the 11th Annual Retroviral Conference.
“Reversion of resistance is gradual and usually incomplete, resulting in the persistence of mixtures of wild-type and resistant variants in plasma HIV RNA,” lead investigator Dr. Susan J. Little of the University of California, San Diego in La Jolla told conference participants.
These findings have important clinical implications for the treatment of these antiretroviral-naïve patients and the highlight the risk of the subsequent transmission of drug resistant variants, she noted.
In a previous study of 394 treatment-naïve patients with primary HIV infection, her group found that about 14% were infected with virus resistant to at least one class of antiretroviral drugs (see Reuters Health report February 7, 2001).
Dr. Little’s group conducted baseline nucleotide sequence analysis of the pol gene to look for major drug-resistant mutations in 12 patients with primary HIV infection who had deferred antiretroviral therapy.
The patients were first evaluated a mean of 56 days after infection, and were followed for a mean of 310 days, she said.
Ten patients had resistance mutations to non-nucleotide reverse transcriptase inhibitors (NNRTI), five had resistance to nucleotide reverse transcriptase inhibitors (NRTI) and four had viral mutations resistant to protease inhibitors (PI).
“Nine out of 10 patients with NNRTI mutations had greater than 10-fold reduced susceptibility to all three NNRTI drugs,” she said.
Most patients had only limited reversion to wild-type, retaining resistant variants in plasma HIV RNA. “Complete reversion by population sequence was demonstrated in only one patient at 2.8 years after initial infection,” Dr. Little told conference participants. None of the four patients with resistant mutations to PI drugs exhibited any reversion during the study period.
“The persistence of all classes of drug-resistant variants provides a prolonged window of opportunity for secondary transmission of drug-resistant variants at a time when plasma virus measures are routinely very high,” Dr. Little said.
“In fact, 2 of the 10 subjects described in this report acquired their 103M [NNRTI] mutation as a secondary transmission from another of the untreated source subjects with primary HIV infection at a time when his viral load ranged from 5.5 to 6.3 logs.”
The “relatively high” replication values of the transmitted resistant variants also suggest that “selective pressures at transmission may in fact favor the transmission of those resistant variants,” she added.
MeSH Headings:Congresses: Health Care Economics and Organizations: Organizations: Genes, pol: Health CareCopyright © 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.
