New Anti-HIV Therapies Needed To Eradicate HIV

n on the reservoir of HIV found within circulating blood cells of patients who had successfully suppressed HIV in their plasma with HAART. The patients were taking various combinations of three to four anti-HIV drugs, including protease inhibitors. With strict adherence to HAART, all had kept HIV below detectable levels for approximately two to three years.

Although evidence has been accumulating that HAART may not wipe out all traces of the virus, it has been unclear what feeds the low-level residual infection. One unanswered question, for example, was whether HAART completely stops viral replication. If not, evidence of viral replication could mean a small but unending source of replicating HIV exists to replenish the reservoir.

To look for evidence of ongoing viral replication, Dr. Zhang and his colleagues studied four sequential cell samples taken from each of eight patients. They examined latently infected cells for changes in the genetic makeup of HIV from sample to sample, which could indicate ongoing replication of HIV. The cells from six patients showed few if any such changes. Over time, however, significant variations in the genetic makeup of HIV's coat protein appeared in cells taken from the other two patients. The changes, the researchers note in their paper, are "likely due to ongoing residual replication, albeit at an exceedingly low level." Studies of various tissue samples and body fluids from one of the two patients confirmed residual HIV replication in cells taken from his lymph nodes, tonsils and gastrointestinal tract.

The Northwestern University group examined at least five sequential blood samples taken from each of five men who also had used HAART to keep HIV below measurable levels for 20 months or more. To investigate the characteristics of the HIV reservoir in these men, they measured changes in the concentrations of HIV DNA and viral RNA in cells over time. They observed that after an initial rapid decline, the

Contact: Laurie K. Doepel
NIH/National Institute of Allergy and Infectious Diseases

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