Acne drug prevents HIV breakout (w/ Video)

March 19, 2010
This is Janice E. Clements, Ph.D., Mary Wallace Stanton Professor of Faculty Affairs, Vice Dean for Faculty, and Professor of Molecular and Comparative Pathobiology at the Johns Hopkins University School of Medicine. Credit: Johns Hopkins Medicine

Johns Hopkins scientists have found that a safe and inexpensive antibiotic in use since the 1970s for treating acne effectively targets infected immune cells in which HIV, the virus that causes AIDS, lies dormant and prevents them from reactivating and replicating.

The drug, minocycline, likely will improve on the current treatment regimens of HIV-infected patients if used in combination with a standard drug cocktail known as HAART (Highly ), according to research published now online and appearing in print April 15 in The . "The powerful advantage to using minocycline is that the virus appears less able to develop because minocycline targets cellular pathways not viral proteins," says Janice Clements, Ph.D., Mary Wallace Stanton Professor of Faculty Affairs, vice dean for faculty, and professor of molecular and comparative pathobiology at the Johns Hopkins University School of Medicine.

"The big challenge clinicians deal with now in this country when treating patients is keeping the virus locked in a dormant state," Clements adds. "While HAART is really effective in keeping down active replication, minocycline is another arm of defense against the virus."

Unlike the drugs used in HAART which target the virus, minocycline homes in on, and adjusts T cells, major immune system agents and targets of . According to Clements, minocycline reduces the ability of T cells to activate and proliferate, both steps crucial to HIV production and progression toward full blown AIDS.

The video will load shortly
Janice E. Clements, Ph.D., Mary Wallace Stanton Professor of Faculty Affairs, Vice Dean for Faculty, and Professor of Molecular and Comparative Pathobiology at the Johns Hopkins University School of Medicine, discusses her team’s discovery that a safe, inexpensive antibiotic will improve on the current treatment regimens of HIV-infected patients. Credit: Johns Hopkins Medicine

If taken daily for life, HAART usually can protect people from becoming ill, but it's not a cure. The is kept at a low level but isn't ever entirely purged; it stays quietly hidden in some . If a person stops HAART or misses a dose, the virus can reactivate out of those immune cells and begin to spread.

The idea for using minocycline as an adjunct to HAART resulted when the Hopkins team learned of research by others on rheumatoid arthritis patients showing the anti-inflammatory effects of minocycline on T cells. The Hopkins group connected the dots between that study with previous research of their own showing that minocycline treatment had multiple beneficial effects in monkeys infected with SIV, the primate version of HIV. In monkeys treated with minocycline, the virus load in the cerebrospinal fluid, the viral RNA in the brain and the severity of central nervous system disease were significantly decreased. The drug was also shown to affect T cell activation and proliferation.

"Since minocycline reduced T cell activation, you might think it would have impaired the immune systems in the macaques, which are very similar to humans, but we didn't see any deleterious effect," says Gregory Szeto, a graduate student in the Department of Cellular and Molecular Medicine working in the Retrovirus Laboratory at Hopkins.

"This drug strikes a good balance and is ideal for HIV because it targets very specific aspects of immune activation."

The success with the animal model prompted the team to study in test tubes whether minocycline treatment affected latency in human T cells infected with HIV. Using cells from HIV-infected humans on HAART, the team isolated the "resting" immune cells and treated half of them with minocycline. Then they counted how many virus particles were reactivated, finding completely undetectable levels in the treated cells versus detectable levels in the untreated cells.

"Minocycline reduces the capability of the virus to emerge from resting infected T cells," Szeto explains. "It prevents the virus from escaping in the one in a million cells in which it lays dormant in a person on HAART, and since it prevents virus activation it should maintain the level of viral latency or even lower it. That's the goal: Sustaining a latent non-infectious state."

The team used molecular markers to discover that minocycline very selectively interrupts certain specific signaling pathways critical for T cell activation. However, the antibiotic doesn't completely obliterate T cells or diminish their ability to respond to other infections or diseases, which is crucial for individuals with HIV.

"HIV requires T cell activation for efficient replication and reactivation of latent virus," Clement says, "so our new understanding about minocyline's effects on a T cell could help us to find even more drugs that target its signaling pathways."

Related Stories

Recommended for you

Researchers use CRISPR to accelerate search for HIV cure

October 25, 2016

Researchers at UC San Francisco and the academically affiliated Gladstone Institutes have used a newly developed gene-editing system to find gene mutations that make human immune cells resistant to HIV infection.

Study unlocks secret of common HIV strain

October 13, 2016

A discovery that the most common variant of the HIV virus is also the "wimpiest" will help doctors better treat millions of individuals around the world suffering from the deadly disease, according to one of the world's leading ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

5 / 5 (1) Mar 20, 2010
Very interesting. I wonder, however, if it is practical to think that people could safely take this antibiotic on a permanent basis. Bone and kidney damage seem likely with long term use.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.