Existing antibiotic might help keep wraps on AIDS virus

Acne drug minocycline inhibits HIV activation in infected immune cells

An inexpensive antibiotic might complement standard drugs in fighting the AIDS virus, a new study shows. The drug, called minocycline, has been used for decades to control acne, but the new findings suggest it inhibits HIV that has infected cells from reactivating and replicating itself. The report will appear in the April 15 Journal of Infectious Disease.

In most people, HIV can be controlled with a drug combination called HAART, short for highly active antiretroviral therapy. But HAART doesn’t wipe out the virus, and stresses on the immune system such as an infection can reactivate the latent virus and trigger its spread.

In the new study, molecular biologist Janice Clements of Johns Hopkins University in Baltimore and her colleagues infected human CD4 T cells with HIV in lab dishes, then added minocycline to some of these batches. After 24 hours, the minocycline-treated cells contained half as much HIV RNA as the other cells, suggesting the drug had inhibited the ability of the virus to replicate.

The scientists also tested minocycline on CD4 T cells obtained from HIV patients who had been treated with HAART. Minocycline again stalled HIV replication, as demonstrated by a 60 percent decline in activity of a key gene that HIV needs to awaken and replicate.

These properties of minocycline add to the drug’s growing résumé. In addition to its role as an acne-fighting antibacterial, minocycline slows inflammation and can limit brain damage. In earlier work, Clements and her colleagues found that minocycline reduced brain inflammation and limited the amount of virus in the brains of monkeys with SIV, the simian version of the AIDS virus. And in the mid-1990s, Dutch scientists found that minocycline, a derivative of tetracycline, knocked down inflammation in rheumatoid arthritis patients.

Although inflammation is a normal immune response, too much causes damage. Minocycline seems to reduce hyperactivation of T cells, key players in inflammation, says immunologist Gregory Szeto of Johns Hopkins, who coauthored the new study.

In a third experiment using healthy CD4 T cells that were activated by the presence of an antibody, Clements, Szeto and their colleagues showed that cells exposed to minocycline made reduced amounts of three inflammatory proteins.

In HIV patients, inflammation can exhaust the immune response and contribute to AIDS progression. But Szeto cautions that inflammation can be accurately evaluated only in the context of a person’s body and not in a cell study such as this.

Meanwhile, minocycline’s brain-protecting attributes have attracted interest (SN 10/13/07, p. 238). HIV can enter the central nervous system and remain dormant there for long stretches. Even as HAART has extended survival in AIDS patients, many now develop cognitive impairments, several studies have shown. Clements estimates that roughly half of HIV patients receiving HAART for more than 10 years have some cognitive damage from the virus.

Because minocycline can enter the brain, it may provide protection to these patients, Clements says.

“Certainly, this could have very positive effects, because HAART drugs have differing abilities to cross the blood-brain barrier,” says virologist Celsa Spina of the Veterans Affairs San Diego Healthcare System and the University of California, San Diego. “That would be a benefit — to reduce HIV activation within the central nervous system.”

At Johns Hopkins and elsewhere, scientists are now testing whether giving HIV patients minocycline benefits them.

Spina cautions that although minocycline has a long track record in acne patients, HIV patients are a very different group. “I would be worried about using something that appears to be a broad-spectrum suppressor of T cell activation,” she says. ”If you have patients who are immune-suppressed but otherwise healthy, you don’t want to subject them to something that’s going to hurt them.” She says patients will require close monitoring in these trials.

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