Association of circulating cytochrome c with clinical manifestations of antiretroviral-induced toxicity

Allison Langs-Barlow; Shanmugapriya Selvaraj; Onyema Ogbuagu; Veronika Shabanova; Eugene D Shapiro; Elijah Paintsil

doi:10.1016/j.mito.2014.11.004

Association of circulating cytochrome c with clinical manifestations of antiretroviral-induced toxicity

Mitochondrion. 2015 Jan:20:71-4. doi: 10.1016/j.mito.2014.11.004. Epub 2014 Nov 28.

Authors

Allison Langs-Barlow¹, Shanmugapriya Selvaraj², Onyema Ogbuagu³, Veronika Shabanova⁴, Eugene D Shapiro⁵, Elijah Paintsil⁶

Affiliations

¹ Department of Pediatrics, Yale School of Medicine, PO Box 208064, New Haven, CT 06520-8064, USA. Electronic address: Allison.Langs-Barlow@yale.edu.
² Department of Medicine, Yale School of Medicine, 330 Cedar St., Boardman 110, PO Box 208056, New Haven, CT 06520-8056, USA. Electronic address: ss_vel28@yahoo.com.
³ Department of Medicine, Yale School of Medicine, 330 Cedar St., Boardman 110, PO Box 208056, New Haven, CT 06520-8056, USA. Electronic address: Onyema.Ogbuagu@yale.edu.
⁴ Center for Analytical Sciences, Yale School of Public Health, 300 George Street, Suite 555, New Haven, CT 06520, USA. Electronic address: Veronika.Shabanova@yale.edu.
⁵ Department of Pediatrics, Yale School of Medicine, PO Box 208064, New Haven, CT 06520-8064, USA; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, 60 College Street, PO Box 208034, New Haven, CT 06520-8034, USA. Electronic address: Eugene.Shapiro@yale.edu.
⁶ Department of Pediatrics, Yale School of Medicine, PO Box 208064, New Haven, CT 06520-8064, USA; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, 60 College Street, PO Box 208034, New Haven, CT 06520-8034, USA; Department of Pharmacology, Yale School of Medicine, Sterling Hall of Medicine, 333 Cedar Street, SHM B-208, New Haven, CT 06520-8066, USA. Electronic address: Elijah.Paintsil@yale.edu.

Abstract

Diagnosis of antiretroviral therapy (ART) toxicity is complicated. Apoptosis has been implicated in ART toxicity. Cytochrome c (Cyt-C) is a mitochondrial protein found in plasma during pro-apoptotic states. We conducted a study of HIV-infected individuals on ART with (cases, n=21) and without (controls, n=21) clinical evidence of toxicity to determine if elevated plasma Cyt-C is associated with ART toxicity. When corrected for CD4 count, viral load, and duration of HIV infection, cases are 7.86 times more likely than controls to have plasma Cyt-C>0.216 ng/mL. Cyt-C could be a useful clinical tool to guide treatment decisions in this population.

Keywords: Antiretroviral therapy; Cytochrome c; Mitochondrial toxicity.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adult
Aged
Anti-Retroviral Agents / administration & dosage
Anti-Retroviral Agents / adverse effects*
Biomarkers / blood*
CD4 Lymphocyte Count
Case-Control Studies
Cytochromes c / blood*
Drug-Related Side Effects and Adverse Reactions / diagnosis*
Drug-Related Side Effects and Adverse Reactions / pathology*
Female
HIV Infections / drug therapy
HIV Infections / pathology
Humans
Male
Middle Aged
Mitochondria / drug effects
Mitochondria / enzymology
Pilot Projects
Plasma / chemistry
Viral Load

Substances

Anti-Retroviral Agents
Biomarkers
Cytochromes c

Abstract

Publication types

MeSH terms

Substances

Grants and funding