In the early 1980’s when the AIDS epidemic first became apparent, there were no medications available to treat the disease. A diagnosis of HIV infection was a death sentence and meant that the patient would definitely develop AIDS and succumb to the disease. In the late 1980’s, zidovudine was developed for the treatment of HIV infection and significantly changed the prognosis for patients infected with the HIV virus. Treatment with zidovudine meant that a patient with HIV infection would be able to live an additional 10-20 years. Zidovudine slowed the progression of the disease, but did not cure it because the virus would develop resistance to the medication. Zidovudine belongs to the class of drugs known as nucleoside analog reverse transcriptase inhibitors (NRTI) HIV is an RNA retrovirus and uses an enzyme, known as reverse transcriptase, to convert it’s RNA to DNA and propagate the infectious cycle. Zidovudine works by inhibiting reverse transcriptase, and disrupts propagation of the HIV virus. Since the initial development of zidovudine, there have been many other drugs developed to treat HIV infection. Patients that were treated with zidovudine are noted to have accelerated aging and often develop heart disease, dementia, and other age related illnesses much sooner that other individuals. Researches lead by Dr. Patrick Chinnery, from Newcastle University in the United Kingdom, have described how NRTI cause accelerated aging in patient treated with these medications. The results of the research were published online in the journal Nature Genetics. The researchers analyzed muscle cells from patients with HIV infection that were treated with NRTI. They found that these patients accumulate somatic mitochondrial DNA mutations that are normally seen much later in life as a result of the aging process. The researchers report that increased somatic mutations are not likely to be caused by increased somatic mutagenesis but instead by accelerated mitochondrial DNA turnover. The authors wrote, “The rapid clonal expansion of somatic [mitochondrial] DNA mutations we observed in NRTI-treated HIV-infected patients provides a plausible mechanism for accelerated aging in treated HIV infection. This is potentially of great importance for the millions of HIV-infected patients in the developing world where these drugs remain the mainstay of therapy and adds weight to a causal role for somatic [mitochondrial] DNA mutations in human aging”. Newer medications that are used to treat HIV infection are not believed to have the same effects but more research is needed for confirmation. In more wealthy nations, zidovudine and other similarly toxic NRTIs are less frequently used, but in Africa and other parts of the world these medications are vital for the treatment of HIV infection. Future research will focus on ways to repair or slow the changes and damage that occures in the somatic mitochondrial DNA that lead to this accelerated aging process.
Brendan A I Payne et al. “Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations” Nature Genetics published online 26 June 2011