A class of HIV drugs might protect against Alzheimer’s


A cohort of people with HIV who took NRTIs (a class of HIV drugs) as part of HIV treatment showed lower rates of Alzheimer’s disease than people without HIV. The team of American researchers behind this study published in the journal of Pharmaceuticals suspect HIV-like sequences in our genome to be associated with the disease and thus these HIV drugs protect against its development.

In our genome there is a significant amount of virus-like DNA sequences (estimated at 8% of its length). They are believed to be an evolutionary leftover from previous pandemics. Once integrated in our genome, they are hard to eliminate, as is HIV DNA, therefore our immune system chose a different approach – ‘block, cripple and lock’. Because of this, most of these sequences are seriously damaged and cannot produce intact viruses but can still produce some viral proteins, including a couple of reverse transcriptase (RT) enzymes, thought to be unique to only two groups of viruses, one of which includes HIV.

Up to recently, it was thought that humans should not and cannot have such enzymes, since its function is to convert RNA back into DNA – a largely risky and unnecessary process for non-viral organisms since it is prone to errors. Therefore, the discovery of an RT gene in human genomes is attributed to past HIV-like infections.



The complete set of genes or genetic material (information) present in a cell or organism.

deoxyribonucleic acid (DNA)

The material in the nucleus of a cell where genetic information is stored.

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 


A protein which speeds up a chemical reaction.

Research suggests these RT enzymes may be still able to introduce random genetic recombinations and amplifications (increasing the copy number of certain harmful genes) in the brain cells causing them to produce dysfunctional proteins that clump up and harm the brains of people with Alzheimer’s disease.

Nucleoside reverse transcriptase inhibitors (NRTIs) are a class of drugs that block HIV’s RT enzyme. Since HIV’s RT is similar to the RTs produced in our cells, these same drugs may have the potential to block them too, possibly protecting against Alzheimer’s disease.

The study

The researchers collected data on three cohorts of people – those with HIV taking NRTIs; those with HIV either on an NRTI-free regimen or off treatment; and a third cohort who were not living with HIV nor taking NRTIs. They followed up each cohort for two years and nine months to see whether NRTIs reduced the rate of Alzheimer’s.

The data came from a large number of people, which reduces the likelihood of these findings being a chance event. Over 46,000 people were included in the cohort of those with HIV on NRTI-containing regimens. There were 33,000 people in the cohort of people with HIV not taking NRTIs and 151,000 people in the cohort without HIV and not taking NRTIs.

Only participants above 60 years of age and without a previous diagnosis of Alzheimer’s disease were included.

The median age in the first two cohorts was similar at 64 and 65 years, while the third cohort – without HIV and not taking NRTIs – was slightly older at 69 years. Over two-thirds of the participants in the first two cohorts were men, while in the third cohort two-thirds were women. Both age and sex can affect Alzheimer’s risk and since the first two cohorts and the third one had differing age and sex profiles, the researchers had to adjust for that in the analysis when deriving their final results.

Alzheimer’s rates per cohort

During the two years and nine months of follow-up, the rate of developing Alzheimer’s was lowest in the first cohort – people with HIV on an NRTI-containing regimen. In this cohort only 2.46 in 1000 people developed Alzheimer's disease.

In the second cohort of those with HIV either on an NRTI-free regimen or off treatment the rate of Alzheimer’s was higher compared to the first cohort, but still lower than the third cohort of those without HIV. However, the difference between this cohort and those without HIV became insignificant when age and sex were added to the analysis. In this cohort the rate of Alzheimer’s was 3.55 in 1000 people.

The third cohort had the highest rate of Alzheimer’s at 6.15 in 1000 people.

Interestingly, a further analysis of the first cohort revealed an increased rate of Alzheimer’s in those taking protease inhibitors (another class of HIV drugs) alongside their NRTIs. However, the difference was not statistically significant and it would be early to make any conclusions.

Concluding thoughts

Although  previous research has linked different viruses and virus-like elements to Alzheimer’s disease – be it directly or indirectly (as a contributing factor) – the condition is multifactorial. Certainly, some viruses and inflammatory conditions have the potential to contribute to the development of the disease. However, genetic, lifestyle and other environmental factors cannot be ruled out.

While NRTIs seem to decrease Alzheimer’s risk, the mechanism may be different from the one proposed in this study. Some NRTIs can suppress the inflammasome (the inflammation complex in the body), which can indirectly protect the brain.

Last but not least, this was a retrospective study (one that collects data on the past medical records of people). Besides, it has a set of limitations such as a relatively short follow-up period and non-ideal match between cohorts with regards to age and sex. Randomised controlled studies would be required to get a more definitive answer to whether NRTIs protect against Alzheimer’s disease in people without HIV.