Meta-Analysis
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Virology. May 12, 2015; 4(2): 147-155
Published online May 12, 2015. doi: 10.5501/wjv.v4.i2.147
Elevated homocysteine levels in human immunodeficiency virus-infected patients under antiretroviral therapy: A meta-analysis
Rafael Deminice, Talita Capoani Vieira Silva, Vitor Hugo Fernando de Oliveira
Rafael Deminice, Talita Capoani Vieira Silva, Vitor Hugo Fernando de Oliveira, Department of Physical Education, State University of Londrina, Londrina 86057-970, Brazil
Author contributions: The study was designed by Deminice R; data were collected and analyzed by Deminice R and Silva TCV; data interpretation and manuscript preparation were undertaken by Deminice R, Silva TCV and de Oliveira VHF; Manuscript preparation Deminice R, Silva TCV and de Oliveira VHF; had final responsibility to the manuscript Deminice R.
Supported by Rafael Deminice is supported by Brazilian grants SETI-PR (Programa Universidade sem Fronteiras, Secretaria da Ciência, Tecnologia e Ensino Superior).
Conflict-of-interest: All authors declared that there is no potential conflict of interests regarding this article.
Data sharing: All data generated during the project will be made freely available via correspondent author e-mail (deminice@ig.com.br). Data will be maintained for a minimum of 10 years. There are no security or licensing related to the expected data, and all data used in the project will be generated directly as a result of the project, without any pre-existing data being used.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Rafael Deminice, PhD, Assistant Professor, Department of Physical Education, State University of Londrina, Rodovia Celso Garcia Cid, Pr 445 Km 380, Campus Universitário, Londrina, Paraná 86057-970, Brazil. deminice@ig.com.br
Telephone: +55-43-33715481 Fax: +55-43-33715481
Received: October 28, 2014
Peer-review started: October 28, 2014
First decision: November 14, 2014
Revised: November 28, 2014
Accepted: March 4, 2015
Article in press: March 5, 2015
Published online: May 12, 2015
Processing time: 184 Days and 15.1 Hours
Abstract

AIM: To evaluate the association between the levels of homocysteine (Hcy), folate, vitamin B12 in human immunodeficiency virus (HIV)-infected patients who were treated with antiretroviral therapy (ART) or not treated with ART.

METHODS: The PubMed and Scielo databases were searched. Eligible studies regarding plasma Hcy level in HIV-infected patients were firstly identified. After careful analysis by two independent researches, the identified articles were included in the review according to two outcomes (1) Hcy, folate and vitamin B12 blood concentration in HIV-infected subjects vs health controls and; (2) Hcy blood concentration in HIV-infected subjects under ART vs not treated with ART. RevMan (version 5.2) was employed for data synthesis.

RESULTS: A total of 12 studies were included in outcome 1 (1649 participants, 932 cases and 717 controls). Outcome 1 meta-analysis demonstrated higher plasma Hcy (2.05 µmol/L; 95%CI: 0.10 to 4.00, P < 0.01) and decreased plasma folate concentrations (-2.74 ng/mL; 95%CI: -5.18 to -0.29, P < 0.01) in HIV-infected patients compared to healthy controls. No changes in vitamin B12 plasma concentration were observed between groups. All studies included in the outcome 2 meta-analysis (1167 participants; 404 HIV-infected exposed to ART and 757 HIV-infected non-ART patients) demonstrated higher mean Hcy concentration in subjects HIV-infected under ART compared to non-ART HIV subjects (4.13 µmol/L; 95%CI: 1.34 to 6.92, P < 0.01).

CONCLUSION: This meta-analysis demonstrated that the levels of Hcy and folate, but not vitamin B12, were associated with HIV infection. In addition, Hcy levels were higher in HIV-infected patients who were under ART compared to HIV-infected patients who were not exposed to ART. Our results suggest that hyperhomocysteinemia should be included among the several important metabolic disturbances that are associated with ART in patients with HIV infection.

Keywords: Antiretroviral therapy; Homocysteine; Folate; Vitamin B12; Human immunodeficiency virus; Acquired immune deficiency syndrome

Core tip: Although antiretroviral therapy (ART) has changed dramatically the speciation of life of human immunodeficiency virus (HIV)-infected patients, it has increased the incidence of chronic diseases, especially cardiovascular diseases. Nowadays, elevated levels of homocysteine have been considered to be an independent risk factor for cardiovascular disease development. Our study demonstrated that the levels of Hcy and folate, were associated with HIV infection, especially for those exposed to ART.