Mitochondrial dysfunctions in HIV infection and antiviral drug treatment

ABSTRACT

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.

KEYWORDS:

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

Article highlights

• Mitochondrial dysfunction is the basis of several side effects caused by HIV infection and antiretroviral drug treatment

• This review explores how HIV interacts with mitochondria to cause mitochondrial dysfunction

• How individual anti-HIV drugs cause mitochondrial dysfunctions

• Drugs whose mitochondrial dysfunctions are yet to be evaluated are also mentioned in this review

• This review provides information in which drugs are main constituents of mitochondrial toxicity which may help in designing novel treatment regimen

This box summarizes key points contained in the article.

Declaration of interest

This work was funded by Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the Department of Biotechnology, New Delhi, India, financial support vide Sanction no BT/PR10319/GBD/27/97/2007.