A safe and inexpensive antibiotic used to treat acne may also be useful for people living with HIV who combine it with standard antiretroviral therapy, according to a research article and an accompanying editorial published in the April 15 issue of The Journal of Infectious Diseases (JID). According to researchers at Johns Hopkins University School of Medicine in Baltimore, minocycline’s anti-inflammatory properties effectively target dormant HIV-infected CD4 cells in the body and, as a result, prevent the virus from reactivating and replicating.
The idea behind using minocycline in combination with ARV treatment came about when Gregory Szeto, a graduate student in the Department of Cellular and Molecular Medicine at Hopkins, and his colleagues learned of research showing that minocycline—a popular broad-spectrum antibiotic frequently used to treat acne—had anti-inflammatory effects on CD4 cells in patients with rheumatoid arthritis and cystic fibrosis.
The researchers also drew upon studies conducted at Hopkins showing that minocycline treatment had multiple beneficial effects in monkeys infected with SIV, the primate version of HIV. The level of SIV in the cerebrospinal fluid, the amount of SIV RNA in the brain and the severity of central nervous system disease in monkeys treated with minocycline were significantly decreased. The drug was also shown to affect CD4 cell activation and proliferation.
In a Hopkins press release and video (see below), Janice Clements, PhD, a professor of molecular and comparative pathobiology at Hopkins and a coauthor of the study, explained that minocycline add-on therapy may help keep the virus locked in a dormant state. “While HAART is really effective in keeping down active replication,” she said, “minocycline is another arm of defense against the virus.”
Another advantage to using minocycline, Clements said, “is that the virus appears less able to develop resistance because minocycline targets cellular pathways not viral proteins.”
The curious effects of minocycline in animal models prompted Szeto’s group to conduct test tube studies to explore how minocycline treatment affects latently infected CD4 cells—inactive immune system cells containing HIV that can be reactivated if ARV treatment is stopped or if doses are missed. The team first isolated inactive HIV-infected CD4 cells and treated half with minocycline. Upon counting the number of reactivated virus particles, Szeto and his colleagues found 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 [CD4] cells,” Szeto said in the press release. “It prevents the virus from escaping in the one in a million cells in which it lays dormant in a person on [ARV therapy], 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 noninfectious state.”
Sustaining the reservoir of latently infected CD4 cells contradicts the work of other research teams hoping to cure the virus, according to an accompanying JID editorial authored by Karen Copeland, PhD, and James Brooks, MD, of the Public Health Agency of Canada. “Considerable research effort has been directed toward purging HIV from latent reservoirs with valproate [Depakote] and other small molecules in the hope of eradicating the virus. The approach of enhancing HIV latency…seemingly runs contrary to the strategy of inducing the virus for eradication purposes. It remains to be seen which approach, if either, will result in long-term clinical benefit for those infected with HIV.”
Janice E. Clements, PhD, on her team's discovery that a safe,
inexpensive antibiotic will improve on current treatment regimens for
people living with HIV.
