title: Elevated homocysteine levels in human immunodeficiency virus-infected patients under antiretroviral therapy: A meta-analysis.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Rafael Deminice, Talita Capoani Vieira Silva, Vitor Hugo Fernando de Oliveira, Department of Physical Education, State University of Londrina, Londrina 86057-970, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Deminice
authors.affiliation: Rafael Deminice, Talita Capoani Vieira Silva, Vitor Hugo Fernando de Oliveira, Department of Physical Education, State University of Londrina, Londrina 86057-970, Brazil.
authors.forename: Talita Capoani Vieira
authors.initials: TC
authors.lastname: Silva
authors.affiliation: Rafael Deminice, Talita Capoani Vieira Silva, Vitor Hugo Fernando de Oliveira, Department of Physical Education, State University of Londrina, Londrina 86057-970, Brazil.
authors.forename: Vitor Hugo Fernando
authors.initials: VH
authors.lastname: de Oliveira
keywords: Acquired immune deficiency syndrome; Antiretroviral therapy; Folate; Homocysteine; Human immunodeficiency virus; Vitamin B12