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Expert Opin Drug Metab Toxicol. 2019 Dec;15(12):1043-1052. doi: 10.1080/17425255.2019.1692814. Epub 2019 Nov 18.

Mitochondrial dysfunctions in HIV infection and antiviral drug treatment.

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Functional Genomics Lab, Centre for Advanced Study, Department of Botany, University of Calcutta, Kolkata, India.


Introduction: With the introduction of highly active anti-retroviral therapy (HAART), treatment of HIV infection has improved radically, shifting the concept of HIV disease from a highly mortal epidemic to a chronic illness which needs systematic management. However, HAART does not target the integrated proviral DNA. Hence, prolonged use of antiviral drugs is needed for sustaining life. As a consequence, severe side effects emerge. Several parameters involve in causing these adverse effects. Mitochondrial dysfunctions were pointed as common factor among them. It is, therefore, necessary to critically examine mitochondrial dysfunction in order to understand the side effects.Areas covered: There are many events involved in causing drug-induced side-effects; in this review, we only highlight mitochondrial dysfunctions as one of the events. We present up-to-date findings on mitochondrial dysfunction caused by HIV infection and antiviral drug treatment. Both in vivo and in vitro studies on mitochondrial dysfunction like change in morphology, membrane depolarization, mitophagy, mitochondrial DNA depletion, and intrinsic apoptosis have been discussed.Expert opinion: Mitochondrial dysfunction is associated with severe complications that often lead to discontinuation or change in treatment regimen. Prior knowledge of side effects of antiviral drugs would help in better management and future research should focus to avoid mitochondrial targeting of antiviral drugs while maintaining their antiviral properties.


HIV; antiretroviral therapy; intrinsic apoptosis; mitochondrial dysfunction; mtDNA depletion

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