Leber's hereditary optic neuropathy triggered by antiretroviral therapy for human immunodeficiency virus

Abstract

Purpose To describe the clinical features of two cases of Leber's hereditary optic neuropathy (LHON) precipitated by antiretroviral treatment for human immunodeficiency virus (HIV) infection. Methods Two cases of LHON (from an expected four new cases a year throughout Australia) were identified in men on treatment for HIV infection. Results Two HIV-infected men were receiving combination antiretroviral therapy that included nucleoside analogues. Both patients carried the 14 484 mitochondrial DNA mutation and were distantly related (seventh cousins). Although both men presented with sequential visual loss typical of LHON and one had a known close relative affected by LHON, the correct diagnosis was delayed in both cases. The final visual outcome was profoundly reduced in both instances and cessation of antiretroviral therapy did not result in recovery of vision in one patient. Conclusion Patients with a family history of LHON who require antiretroviral treatment should be warned of the high risk of severe visual loss. The underlying mechanism of antiretroviral side effects may help characterize the other trigger factors for LHON.

The mitochondrial pharmacogenomics of haplogroup T: MTND2*LHON4917G and antiretroviral therapy-associated peripheral neuropathy

“…41,42 Case reports of HIV-infected individuals with primary LHON mutations documented onset of the disease phenotype after exposure to antiretroviral therapy. [43][44][45][46][47] These reports suggested that drug exposure unmasked a genetic predisposition to this neurodegenerative process. Non-genetic factors are clearly important in the development of NRTI-associated PN.…”

Late onset of Leber's hereditary optic neuropathy precipitated by anaemia

“…Smoking and high alcohol consumption have been implicated but disputed. 3,4 Head or ocular trauma, 1 childbirth alone or complicated by postpartum haemorrhage, 1 onset of diabetes mellitus, 5 vitamin B 12 deficiency, 6 antiretroviral therapy, 7,8 cyanide toxicity, 9 carbon monoxide poisoning, 10 and ephedra alkaloids 11 have all been implicated.…”

Mitochondrial disorders: aetiologies, models systems, and candidate therapies

“…Interindividual and intertissue variations in levels of heteroplasmy (ratio of mutant:wild type mtDNA) can greatly influence the severity of many mitochondrial diseases, including LHON [22]. Mitochondrial disorders are subject to many other factors that can influence the phenotype, including environmental modifiers; risk factors for LHON include smoking, solvent exposure, and antiretroviral medication [23][24][25]. Genetic modifiers may also impact on disease phenotype [26,27]; for example, an X-linked modifier locus for LHON has been reported [26].…”