Clinical

HCV diversity may increase with HAART in coinfected patients

Last Updated: 2004-04-20 16:25:05 -0400 (Reuters Health)

By Megan Rauscher

NEW YORK (Reuters Health) - In patients coinfected with HIV and hepatitis C virus (HCV), suppression of HIV infection with highly active antiretroviral therapy (HAART) appears to result in increased immunologic selection pressure against HCV leading to increased diversity of HCV quasi species, according to a report in the April 15th issue of The Journal of Infectious Diseases.

In the AIDS Clinical Trials Group (ACTG) 383, a prospective study evaluating virologic trends among HIV-HCV-coinfected subjects initiating HAART, successful suppression of HIV and improvement in CD4 counts led to an increase in HCV replication (see Reuters Health report October 22, 2002).

"This was surprising and counterintuitive," Dr. Raymond T. Chung told Reuters Health, "and led us to ask the question: 'What happens to the nature of the HCV sequences with implementation of HAART?'"

"We need to be mindful that HCV RNA can actually increase in some patients who are treated with HAART," Dr. Chung from Massachusetts General Hospital in Boston said. "While we may be improving HIV disease with HAART, we may unwittingly be [contributing to] HCV-related liver disease."

In the team's current study, Dr. Chung and colleagues characterized over a 48-week period the diversity of HCV quasi species at several key genomic regions in 11 patients in ACTG 383 who were successfully treated with HAART.

"We saw evolution of variability in one of the key contact regions between the immune system and HCV called the hypervariable region," he said. "This region evolved on HAART far more than any neighboring genomic regions studied," he continued.

"Our observations demonstrate that reconstituted immune selection pressures are being applied on HCV with HAART, but clearly it is not enough to corral HCV and clear it or, in many cases, to even reduce it," Dr. Chung continued. "So there must be some compensatory means by which HCV expands its repertoire and its diversity may actually increase during HAART," he theorized.

Studies are planned to look at HCV responses in the setting of HAART. The results of these studies will be of "great interest," Dr. Chung said.

J Infect Dis 2004;189:1472-1481.