HIV drugs can lead to premature ageing of mitochondrial DNA
By Mehmet Fidanboylu

New research has revealed that a group of generic anti-HIV drugs may be linked to premature ageing. The study, which was carried out by UK scientists at the Institute of Genetic Medicine at Newcastle University, could explain why people treated with this class of drugs sometimes show signs of age-related conditions, such as heart disease and dementia.

The researchers studied muscle cells taken from people with HIV who had previously taken drugs known as nucleoside analogue reverse-transcriptase inhibitors (NRTIs) and found that DNA in the mitochondria of their cells had accumulated a number of errors that was more comparable to healthy people 20 or 30 years older.

'The DNA in our mitochondria gets copied throughout our lifetimes and, as we age, naturally accumulates errors. We believe that these drugs accelerate the rate at which these errors build up', said Professor Patrick Chennery, who led the study, adding: 'Over the space of, say, ten years, a person's mitochondrial DNA may have accumulated the same amount of errors as a person who has natural aged twenty or thirty years'.

NRTIs were a major breakthrough in the battle against HIV when they were developed in the late 1980s. But side-effects such as premature ageing and frailty have meant that they have been replaced by a cocktail of more recent drugs. However, NRTIs are generally favoured over these new drugs in developing countries due to their lower costs.

Until now it has not been clear why NRTIs, which include AZT or zidovudine, have these side-effects. 'HIV clinics were seeing patients who had otherwise been successfully treated but who showed signs of being much older than their years. This was a real mystery', said Professor Chinnery, 'but colleagues recognised many similarities with patients affected by mitochondrial diseases... and referred them to our clinic'.

Defects in mitochondrial DNA are often seen in age-related conditions, although it is not yet known whether this is a cause or consequence of taking the drugs.

It was estimated in 2009 that 33.3 million people had HIV, and of these 22.5 million live in Africa. The researchers were keen to stress that while NRTIs do sometimes have side-effects, not taking them would be worse: 'These drugs may not be perfect, but we must remember that when they were introduced they gave people an extra ten or twenty years when they would otherwise have died. In Africa, where the HIV epidermis has hit hardest and where more expensive medications are not an option, they are an absolute necessity', said Dr Brendan Payne, a co-author of the study.

The researchers will now look at how the damage believed to be caused by the drugs can be repaired. The study was published in Nature Genetics.

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