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Chapter 7 : Mitochondrial Dysfunction and Lactic Acidosis in HIV Disease
Authors:
Ashok Verma1,
Jorge Pardo2
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Affiliations:
1: Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136;
2: Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136
Content Type: Monograph
Publication Year:
2009
Category: Viruses and Viral Pathogenesis
Book DOI:
10.1128/9781555815691
Chapter DOI:
10.1128/9781555815691.ch7
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Mitochondrial Dysfunction and Lactic Acidosis in HIV Disease, Page 1 of 2
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Abstract:
Mitochondria differ from other subcellular organelles in that they contain their own DNA (mitochondrial DNA [mtDNA]). In mitochondrial disorders, not only does energy failure in tissues and organs result, with a variety of clinical symptoms, but the metabolic block at the end of the anaerobic glycolysis can also lead to excessive pyruvate and lactate accumulation. Lactic acidosis, therefore, can be a manifestation of mitochondrial dysfunction. Symptomatic hyperlactatemia associated with antiretroviral therapy is linked to the mitochondrial respiratory-chain impairment in HIV disease. The recent availability of antiretroviral drugs has substantially reduced HIV-associated mortality and morbidity through decreased viral burden and immune restoration. Mitochondria are the site of generation of most of the cellular ATP pool. The conversion of one molecule of glucose to pyruvate or lactate is associated with the net formation of two molecules of ATP. Nucleoside analog reverse transcriptase inhibitors (NRTI)-related mitochondrial toxicity appears to be the major factor responsible for hyperlactatemia and lactic acidosis in patients with HIV disease. All metabolic acidoses have profound effects on the respiratory, cardiac, and nervous system. It seems essential to discontinue all antiretroviral drugs at the time of NRTI-associated lactic acidosis (NALA) diagnosis; however, surviving patients often need to continue antiretroviral therapy.
Citation:
Verma A, Pardo J.
2009.
Mitochondrial Dysfunction and Lactic Acidosis in HIV Disease,
p 87-93.
In
Goodkin K, Shapshak P, Verma A (ed),
The Spectrum of Neuro-AIDS Disorders.
ASM Press, Washington, DC.
doi: 10.1128/9781555815691.ch7
Figures
Mitochondrial Dysfunction and Lactic Acidosis in HIV Disease
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Citation:
Verma A, Pardo J.
2009.
Mitochondrial Dysfunction and Lactic Acidosis in HIV Disease,
p 87-93.
In
Goodkin K, Shapshak P, Verma A (ed),
The Spectrum of Neuro-AIDS Disorders.
ASM Press, Washington, DC.
doi: 10.1128/9781555815691.ch7
/content/10.1128/9781555815691.ch07.ch07fig01
FIGURE 1.
Mechanism of NRTI-induced mitochondrial toxicity and lactate accumulation. –, inhibition; +, potentiation.
10.1128/9781555815691/ch07fig1_thmb.gif
10.1128/9781555815691/ch07fig1.gif
FIGURE 1.
Mechanism of NRTI-induced mitochondrial toxicity and lactate accumulation. –, inhibition; +, potentiation.
Citation:
Verma A, Pardo J.
2009.
Mitochondrial Dysfunction and Lactic Acidosis in HIV Disease,
p 87-93.
In
Goodkin K, Shapshak P, Verma A (ed),
The Spectrum of Neuro-AIDS Disorders.
ASM Press, Washington, DC.
doi: 10.1128/9781555815691.ch7
/content/10.1128/9781555815691.ch07.ch07fig02
FIGURE 2.
The Cori cycle.
10.1128/9781555815691/ch07fig2_thmb.gif
10.1128/9781555815691/ch07fig2.gif
FIGURE 2.
The Cori cycle.
Citation:
Verma A, Pardo J.
2009.
Mitochondrial Dysfunction and Lactic Acidosis in HIV Disease,
p 87-93.
In
Goodkin K, Shapshak P, Verma A (ed),
The Spectrum of Neuro-AIDS Disorders.
ASM Press, Washington, DC.
doi: 10.1128/9781555815691.ch7
/content/10.1128/9781555815691.ch07.ch07fig03
FIGURE 3.
Management of NRTI-associated hyperlactatemia.
10.1128/9781555815691/ch07fig3_thmb.gif
10.1128/9781555815691/ch07fig3.gif
FIGURE 3.
Management of NRTI-associated hyperlactatemia.
Citation:
Verma A, Pardo J.
2009.
Mitochondrial Dysfunction and Lactic Acidosis in HIV Disease,
p 87-93.
In
Goodkin K, Shapshak P, Verma A (ed),
The Spectrum of Neuro-AIDS Disorders.
ASM Press, Washington, DC.
doi: 10.1128/9781555815691.ch7
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