Acne Drug Prevents HIV Breakout'
BALTIMORE, March 18 (AScribe Newswire) -- 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 Active Antiretroviral Therapy),
according to research published now online and appearing in print April 15
in The Journal of Infectious Diseases. "The powerful advantage to using
minocycline is that the virus appears less able to develop drug resistance
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 HIV 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
HIV infection. 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.
If taken daily for life, HAART usually can protect people from
becoming ill, but it's not a cure. The HIV virus is kept at a low level but
isn't ever entirely purged; it stays quietly hidden in some immune cells. 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."
The research was supported by grants from the National Institutes of
Health. Authors of the paper, in addition to Clements and Szeto, are Angela
K. Brice, Sheila A. Barber and Robert F. Siliciano, all of Johns Hopkins.
Also, Hung-Chih Yang of National Taiwan University Hospital.
On the Web:
http://www.hopkinsm edicine.org/ mcp/faculty_ webpages/ clements. html
http://www.hopkinsm edicine.org/ mcp/Retrovirus/
http://www.journals .uchicago. edu/toc/jid/ current
Related Video:
http://www.youtube. com/watch? v=C_ImNAEpOHY Janice E.
Clements, Ph.D., on her team's discovery that a safe, inexpensive antibiotic
will improve on the current treatment regimens of HIV-infected patients.
"Fascinating idea here. Might explain why minocycline helps cfs and Lyme
patients apart from, or along with, killing bacteria."
Source: Paula Carnes
Posted at: [cfs_research] Minocycline prevents HIV breakout
