Adding raltegravir does not clear persistent low-level HIV-1 viremia
NEW YORK (Reuters Health) Mar 04 - Adding the integrase inhibitor raltegravir to combination antiretroviral therapy does not eliminate persistent low-level HIV-1 viremia, according to a report in the March 15th Clinical Infectious Diseases.
"The persistence of viremia despite antiretroviral intensification suggests that residual viremia is not the product of ongoing cycles of HIV replication," Dr. Frank Maldarelli from National Institutes of Health, Bethesda, Maryland told Reuters Health by email. "In such a scenario, HIV eradication will require new approaches to complement combination antiretroviral therapy."
Dr. Maldarelli and colleagues investigated the effects of therapy intensification with raltegravir in 10 HIV patients with persistent viremia who were receiving standard combination antiretroviral therapy.
No patient had a decline in HIV-1 RNA during the intensification period, and none had any rebound in viral level after raltegravir was stopped.
All patients had therapeutic levels of raltegravir by day 14 of intensification, with a mean raltegravir concentration 30-fold higher than the reported 95% inhibitory concentration of 33 nmol/L.
Raltegravir did not produce any significant adverse events.
"These data suggest that, in our study participants, HIV-1 was not derived from the rapidly cycling short-lived cells (half-life, 1-10 days) that are responsible for (more than 99%) of episodes of viremia observed in untreated individuals," the investigators say.
"We are investigating the nature of persistent viremia itself using detailed sequencing techniques to characterize the population genetics of the HIV present after prolonged suppression," Dr. Maldarelli said. "We are (also) characterizing host immune responses during long term suppression of viremia to determine whether the degree of immune activation correlates with the level of persistent viremia."
By Will Boggs, MD
Clin Infect Dis 2010.
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