Clinical and pathological features of mitochondrial DNA deletion disease following antiretroviral treatment

Abstract

This retrospective case series, describes the clinical, histochemical, molecular, and imaging findings of the first 4 such patients treated HIV infection and evidence of mitochondrial dysfunction. Patients 1, 2, and 3 had significant levels of COX-deficient skeletal muscle fibers consistent with mitochondrial myopathy. Although the overall frequency of COX-deficient fibers in patient 4 was low, the presence of somatic mtDNA mutations and abnormal muscle bioenergetics suggests he also had a mild mitochondrial myopathy. In all cases, the observed mtDNA defect comprised mtDNA deletions rather than an mtDNA depletion as reported historically. This argues for the importance of previous rather than current NRTI exposure. Therefore, it was suggest that in HIV infected patients presenting with neuromuscular symptoms, the possibility of an acquired mitochondrial defect should continue to be considered in those patients with a relevant treatment history. Those patients with historical exposure to the polymerase γ–inhibiting dideoxynucleoside analogs are particularly worthy of further investigation