Nucleoside reverse transcriptase inhibitors HIV drugs give ‘substantial’ check on Alzheimer’s

University of Virginia (UVA) scientists are set to pursue randomised clinical trials to examine the potential for a class of HIV drugs – nucleoside reverse transcriptase inhibitors (NRTIs) – to prevent Alzheimer’s disease after having found that patients that have been taking these drugs are much less likely to develop the disease.

NRTIs prevent replication of the HIV virus in the body and Ambati’s team had previously identified that these drugs can also prevent the activation of inflammasomes – which are cytosolic multiprotein complexes of the innate immune system responsible for the activation of inflammatory responses and cell death.

These proteins are associated with the development of Alzheimer’s disease and so Dr. Jayakrishna Ambati’s team at UVA examined whether patients taking inflammasome-blocking drugs were less likely to develop Alzheimer’s.

The team had previously identified a possible mechanism where the HIV drugs – such as the commonly prescribed Truvada and Vemlidy – could prevent Alzheimer’s, prompting them to analyse two of the nation’s largest health insurance databases to evaluate Alzheimer’s risk among patients prescribed the NRTIs medications.

In one dataset, the Alzheimer’s risk was seen to decrease 6% every year the patients took the medication and in the other, the annual fall was 13%.

“It’s estimated that [more than] 10 million people around the world develop Alzheimer’s disease annually,” said Ambati, who is founding director of UVA’s Center for Advanced Vision Science and is the DuPont Guerry III Professor in the University of Virginia School of Medicine’s Department of Ophthalmology.

“Our results suggest that taking these drugs could prevent [around] one million new cases of Alzheimer’s disease [globally] every year.”

The team reviewed data from the US Veterans’ Health Administration Database – totalling 24 years but heavily skewed towards men – alongside 14 years of data in the MarketScan database of commercially-insured patients, a more representative dataset of the US population.

The study cohort included patients who were 50 years old and older who were taking NRTIs medications, meaning either HIV or hepatitis B patients but excluded patients with an Alzheimer’s diagnosis. Using this methodology the team identified more than 270,000 patients then looking for how many went on to develop Alzheimer’s.

Even adjusting for factors such as whether patients had other pre-existing medical conditions, the study determined that the reduction in Alzheimer’s risk among patients who were taking NRTIs was reported to be ‘significant and substantial’.

Patients taking other types of HIV medications – not NRTIs – did not show the same reduction in Alzheimer’s risk. Consequently, the study team has said that NRTIs warrant clinical trial testing to determine their ability to prevent the onset of Alzheimer’s. 

With Alzheimer’s rates climbing dramatically the benefits could be profound, with the number of people living with Alzheimer’s expected to double by 2050. In the US alone, the estimated annual cost of Alzheimer’s and dementia care could rise from $360 billion to almost $1 trillion across the same period, according to the US Alzheimer’s Association.