Scientists made have discovered a significant weapon in battling HIV.
According to a March 18 press release from Johns Hopkins University School of Medicine, an inexpensive antibiotic in use since the 1970s for treating acne effectively targets infected immune cells with HIV.
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 said. “While HAART is really effective in keeping down active replication, minocycline is another arm of defense against the virus.”
The release goes on to say that 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.
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.
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,” says Gregory Szeto, a graduate student in the Department of Cellular and Molecular Medicine working in the Retrovirus Laboratory at Hopkins. “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.”
Studies have not shown that the antibiotic completely obliterates T cells or diminishes their ability to respond to other infectious diseases, which is crucial for those 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 drug could become an important co-medication for HIV-positive persons on antiretroviral therapy, the report continues. Currently, the use of powerful — and expensive — antiretroviral medications are able to slow or stop the replication of HIV in the human body. But it has long been known that while the drugs suppress the virus, they do not stop it. And if a person on the medications stops, the virus soon rebounds. That new viral population is often immune to the previous drug therapy combination.
Researchers say the discovery could be a promising step toward more effective treatment.
