By Skip Connett
Special To BioWorld Today
GENEVA — Pushing viral loads as low as possible and as fast as possible are the most important determinants of sustained success with antiretroviral therapy in 1998.
But even that strategy apparently fails to rid the body of small pools of latent virus and may require boosting the immune system or other novel approaches if patients are ever to free themselves of lifelong medication.
Study data presented by a diverse group of researchers at the 12th World AIDS Conference Tuesday and Wednesday confirmed that drug regimens sending a patient's viral load to undetectable levels at a faster rate had a longer duration of suppression.
At the same time, those patients who could not reach viral load suppression below 50 copies cannot sustain undetectable levels for a long period, said Douglas Richman, a leading AIDS researcher at the University of Southern California, in San Diego.
"People who have greater than 50 copies reflect ongoing replication," he reported at the conference. "In those people who even have a couple hundred copies, contrasted to those who have less than 50, new drug-resistant mutations can appear, albeit very slowly."
As a practical matter, the results question whether less sensitive assays — those that cannot measure virus down to 50 copies — are adequate for good treatment management.
"I would argue that the more sensitive assays are the way we want to go in managing patients on antiretroviral therapy," Richman said.
But even in patients who have no detectable virus using the most sensitive assays, scientists have found in the past year that HIV persists in latent form in small reservoirs of resting CD4 T cells.
The finding is a setback for earlier speculation that highly active antiretroviral therapy (HAART) could eventually eradicate the virus and treatment could be stopped.
"Despite situations where plasma viremia is completely suppressed, even using the most sensitive assays repeatedly, there is residual virus replication," said David Ho, director of Aaron Diamond AIDS Institute, in New York.
Researchers at the U.S. National Institute of Allergy and Infectious Diseases (NIAID) had more bad news to share. The latent pools of infected cells are established extremely early in the course of infection and are not significantly diminished with HAART.
"We have shown that initiating HAART as soon as 10 days after the onset of the symptoms of acute HIV infection does not prevent the formation of latent reservoir of virus," said Anthony Fauci, NIAID director. "By the time high levels of HIV are detectable in the blood, the virus probably has spread to the lymphoid organs and established a pool of latently infected cells."
Fauci presented evidence from nearly a dozen patients showing that treatment had little or no impact on reducing the amount of latent virus.
The NIAID's findings, however, contradict studies at the Aaron Diamond AIDS Institute. In a similar number of patients treated soon after infection, researchers there were able to show a slow decay of the reservoirs.
Ho could not explain the reasons for the different findings, except that his patients were treated earlier in the course of infection. The fact that the virus is still replicating in the face of HAART underscores a point driven home at the conference: the potency of antiretroviral regimens has been overestimated.
"In looking at the hurdles to viral eradication I would rather have less of this latency problem and more of the drug potency problem because this we know how to do better," Ho explained. "With the new agents coming along it is easier for us to deal with than regulating the immune system."
How to diminish latent pools of HIV is a new field of study but already researchers at NIAID are looking at the possibility of "flushing out" the virus by targeting infected CD4 T cells with antibodies or with combinations of cytokines, such as interleukin-2.
"In our in vitro studies we have shown that it is indeed possible to decrease the number of latently infected cells, but a single round of purging doesn't completely eliminate the virus," Fauci said. *