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29 June 2011
HIV drugs causing premature aging
by George Atkinson

Health scientists have discovered that a class of anti-retroviral drugs used to treat HIV in Africa and low income countries can cause premature aging. The study, appearing in Nature Genetics, shows that the drugs damage DNA in the patient's mitochondria - the 'batteries' which power their cells.

The findings may help explain why HIV-infected people treated with antiretroviral drugs sometimes show advanced signs of frailty and diseases such as cardiovascular disease and dementia at an early age.

The drugs, known as nucleoside analogue reverse-transcriptase inhibitors (NRTIs - of which the most well known is Zidovudine, or AZT), were the first class of drug developed to treat HIV.

In wealthy countries, such as Europe and North America, the older NRTIs are used less commonly now due to concerns over toxicity and side-effects when taken over a long period of time. However, as they are now off-licence and hence relatively cheap, the drugs have proved to be an important lifeline for people infected with HIV in Africa and low income countries.

"HIV clinics were seeing patients who had otherwise been successfully treated but who showed signs of being much older than their years. Colleagues recognised many similarities with patients affected by mitochondrial diseases - conditions that affect energy production in our cells - and referred them to our clinic," explained Professor Patrick Chinnery, from the Institute of Genetic Medicine at Newcastle University.

Mitochondria are the 'batteries' in our cells which provide them with the energy to carry out their functions. During natural human ageing, these mitochondria acquire mutations, though it is unclear whether these mutations are a cause of ageing or a consequence.

In an attempt to understand what was happening at a cellular level, Chinnery studied muscle cells from HIV-infected adults, some of whom had previously been given NRTIs. He found that patients who had been treated with NRTIs - even as long ago as a decade previously - had damaged mitochondria which resembled that of a healthy aged person.

"The DNA in our mitochondria gets copied throughout our lifetimes and, as we age, naturally accumulates errors," explained Professor Chinnery. "We believe that these HIV drugs accelerate the rate at which these errors build up. So 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 naturally aged twenty or thirty years. What is surprising, though, is that patients who came off the medication many years ago may still be vulnerable to these changes."

Although the drugs may not be perfect, the researchers said they were still of great benefit. "In Africa, where the HIV epidemic has hit hardest and where more expensive medications are not an option, they are an absolute necessity," the researchers conclude.

Related:
HIV treatments may prematurely age brain

Source: Wellcome Trust




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