Rooting out hidden HIV

Drugs currently used to suppress HIV, the AIDS virus, work only on actively replicating viral particles in the blood. When viruses lie dormant in a cell, they can escape the drugs’ dragnet.

Researchers report in the Aug. 13 Lancet that a novel combination of drugs can significantly reduce the number of these cellular safe houses in patients.

The new, three-step strategy combines a standard “cocktail” of HIV drugs to knock down active virus circulating in a patient, another drug that blocks viral entry into uninfected cells, and finally a drug intended to root out dormant HIV.

David M. Margolis, a physician and virologist at the University of North Carolina at Chapel Hill, and his colleagues recruited four HIV-positive volunteers who had been taking a standard regimen of drugs for at least 2 years. For 4 weeks, each patient received twice-daily injections of enfuviritide, which inhibits HIV from invading fresh CD4 T cells—the primary cells that HIV commandeers. Then, the patients took valproic acid pills for 3 months. Previous lab tests had suggested that valproic acid could rouse HIV resting in CD4 T cells.

In three of the four volunteers, the number of CD4 T cells harboring HIV dropped by three-fourths. In the other volunteer, the decrease was closer to one-fourth.

The goal, Margolis says, “is to get rid of [all] infected CD4 T cells.” Leaving any cells behind could allow the infection to reemerge, he notes.

“These results, though preliminary, merit further urgent study,” says Jean-Pierre Routy of Royal Victoria Hospital in Montreal, writing in the journal issue reporting the new results.

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