New York, Dec 17, 2016: Antiretroviral drugs have been life-changing therapies for HIV patients, but they can have significant side effects including neuronal degeneration, which can be manifested as forgetfulness, confusion and behavioural and motor changes, says a study.
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.
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“Protease inhibitors are very effective antiviral therapies, but they do have inherent toxicities,” said senior author on the study Kelly Jordan-Sciutto, Professor at University of Pennsylvania School of Dental Medicine in the US.
The drugs prompt an increase in levels of the enzyme that cleaves the amyloid precursor protein, APP, to produce beta amyloid, which is responsible for the damage to neurons.
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Notably, inhibiting that enzyme, called BACE1, protected human and rodent brain cells from harm, suggesting that targetting this mechanism with a new drug could minimise damage to neurons in patients on antiretroviral therapies.
“Our findings may cause us to rethink how we’re using these drugs and even consider developing an adjunctive therapy to reduce some of these negative effects,” Jordan-Sciutto noted.
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To determine whether and how neuronal damage arises from drug treatment and to ascertain the enzyme BACE1’s role, the team investigated the effects of protease inhibitors in two animal models, then probed the mechanism of action in cells in culture.
The findings appeared in the American Journal of Pathology. (IANS)
A London man appears to be free of the AIDS virus after a stem cell transplant, the second success including the “Berlin patient,” doctors reported.
The therapy had an early success with Timothy Ray Brown, a U.S. man treated in Germany who is 12 years post-transplant and still free of HIV. Until now, Brown is the only person thought to have been cured of infection with HIV, the virus that causes AIDS.
The latest case “shows the cure of Timothy Brown was not a fluke and can be recreated,” said Dr. Keith Jerome of Fred Hutchinson Cancer Research Center in Seattle who had no role. He added that it could lead to a simpler approach that could be used more widely.
The case was published online Monday by the journal Nature and will be presented at an HIV conference in Seattle.
The patient has not been identified. He was diagnosed with HIV in 2003 and started taking drugs to control the infection in 2012. It’s unclear why he waited that long. He developed Hodgkin lymphoma that year and agreed to a stem cell transplant to treat the cancer in 2016.
With the right kind of donor, his doctors figured, the London patient might get a bonus beyond treating his cancer: a possible HIV cure.
Doctors found a donor with a gene mutation that confers natural resistance to HIV. About 1 percent of people descended from northern Europeans have inherited the mutation from both parents and are immune to most HIV. The donor had this double copy of the mutation.
That was “an improbable event,” said lead researcher Ravindra Gupta of University College London. “That’s why this has not been observed more frequently.”
The transplant changed the London patient’s immune system, giving him the donor’s mutation and HIV resistance.
The patient voluntarily stopped taking HIV drugs to see if the virus would come back.
Usually, HIV patients expect to stay on daily pills for life to suppress the virus. When drugs are stopped, the virus roars back, usually in two to three weeks.
That didn’t happen with the London patient. There is still no trace of the virus after 18 months off the drugs.
Brown said he would like to meet the London patient and would encourage him to go public because “it’s been very useful for science and for giving hope to HIV-positive people, to people living with HIV,” he told The Associated Press Monday.
Stem cell transplants typically are harsh procedures which start with radiation or chemotherapy to damage the body’s existing immune system and make room for a new one. There are complications too. Brown had to have a second stem cell transplant when his leukemia returned.