HIV treatment may have negative impact on brain

New York: Coming up with effective means of treating HIV has been a major challenge for medical experts across the globe, as reports of further advances in the field emerge from time to time.

But Antiretroviral drugs - life-changing therapies for HIV patients - may take a toll on the patient's brain, according to scientists who found that the medicines lead to forgetfulness, confusion and behavioural changes.

These drugs lead to Neurodegeneration which is umbrella term for the progressive loss of structure or function of neurons, including death of neurons.

Certain protease inhibitors, among the most effective HIV drugs, lead to the production of the peptide beta amyloid, often associated with Alzheimer’s disease, the study found.

Researchers from the University of Pennsylvania in the US have now pinpointed some of the key players in causing neuronal damage. The research suggests that certain protease inhibitors, among the most effective HIV drugs, lead to the production of the peptide beta amyloid, often linked to Alzheimer's disease.

Notably, inhibiting that enzyme, called 'BACE1', protected human and rodent brain cells from harm, suggesting that targeting this pathway with a new drug could minimise damage to neurons in patients on antiretroviral therapies.

"Protease inhibitors are very effective antiviral therapies, but they do have inherent toxicities," said Kelly Jordan-Sciutto, professor at University of Pennsylvania. 

Protease inhibitors such as ritonavir and saquinavir are a key part of the drug cocktail that has reduced mortality in HIV-infected people by 50%. These protease inhibitors are widely used in Africa and other developing areas hit hard by HIV/AIDS. They work by blocking viral enzymes necessary for creating infectious particles that allow the virus to spread through the body.

Previous research have shown that protease inhibitors can have toxic effects on the central nervous system. One study, demonstrated that they triggered the activation of stress-response pathways, including oxidative stress and a process called the unfolded-protein response, or UPR. The study appears in the American Journal of Pathology.