The study, by Dr Jeffrey Rumbaugh, looked at two proteins, called Tat and gp120, that are part of the virus that causes HIV infection and that are implicated in the development of HIV dementia, according to Dr Rumbaugh.
HIV is the only virus that makes Tat and gp120, which are produced during its normal life cycle, though other viruses make similar proteins. Dementia is a common side effect of long-term HIV infection, but there are no known specific treatments for this complication.
According to Dr Rumbaugh, Tat and gp120 are believed to cause dementia by reducing the expression of a brain chemical called EAAT-2 (excitatory amino acid transporter-2). EAAT-2 absorbs the neurotransmitter glutamate from the space between neurons (the synapse), thereby preventing excess neuronal excitation, which in turn can cause cell death and brain damage.
Ceftriaxone, used to treat pneumonias, sexually transmitted diseases, bacterial meningitis and other infections, is a known stimulator of EAAT-2 expression and protects against neuronal injury in mice with nervous system disorders. To test ceftriaxone’s potential in HIV, Dr Rumbaugh and colleagues grew human neuronal cell cultures in a lab from existing human neuron cell lines, treated them with a range of doses of ceftriaxone, and exposed them to Tat or gp120.
They found that the antibiotic protected the neurons against both HIV proteins. The dose of ceftriaxone needed for protection was well within the range currently used for treatment of bacterial infections.
“These results indicated that this class of drugs may prove effective in treating HIV patients with dementia,” Dr Rumbaugh said. “We hope this research might help many patients with other forms of dementia, such as Alzheimer’s, and infections of the brain, like herpes encephalitis and West Nile encephalitis.”
“However,” he continued, “it will require a lot more development before drugs like these can be used even to treat patients with HIV dementia, let alone to treat patients with other neurological diseases.”
Dr Rumbaugh also added that, although ceftriaxone is FDA approved and could be used at any time by patients suffering from HIV dementia, there is not yet enough data to support doing so. Clinical trials in this indication are not yet on the horizon.