Older ARVs associated with premature ageing

Certain antiretroviral (ARV) drugs commonly used in the developing world may be responsible for premature ageing, according to the authors of a new study published in the journal, Nature Genetics. Newer, less toxic but more expensive ARVs are more commonly used in the Western world.



Nucleoside analogue reverse-transcriptase inhibitors (NRTIs) - including Zidovudine, Lamivudine and Abacavir - have enabled millions of people living with HIV to prolong their lives. The UN World Health Organization has recommended that countries phase out Stavudine, an NRTI commonly used in Africa, due to long-term, irreversible side effects.



"We noticed that people in their 40s who had been on NRTIs for the past several years had signatures of ageing in their muscles commonly found in healthy people in their 70s and 80s," said Prof Patrick Chinnery of the University of Newcastle in the UK, one of the study's lead authors.



The researchers studied skeletal muscle from 33 HIV-infected adults, all aged 50 years or under, and 10 uninfected control subjects of comparable age. They found that in patients on NRTI treatment there was an expansion in mutations of mitochondrial DNA - the energy-producing part of the cell - similar to the mutations found in healthy older individuals.



"What we saw in our study is similar to patterns described by people who have been on ART [antiretroviral therapy] for a long time," said Chinnery.



Studies have found that despite a significant drop in mortality, people living with HIV are often affected by an increased risk of non-AIDS complications, including osteoporosis and heart attacks, which undermine their life-expectancy.



"The findings suggest that we need to look carefully at the effects of these drugs because some of the diseases caused by the abnormalities - diabetes, heart failure and so on - are serious and can cause progressive disability," Chinnery noted.



"But at the same time, clearly the patients need their drugs in order to keep them alive... but our study suggests that it may be beneficial to move to newer classes of drugs."



Chinnery said there was a need to conduct prospective studies on the likely effects of long-term use of different ARVs in order to catch and address potentially harmful side effects.



kr/he