Oxidative Stress Predicts All-Cause Mortality in HIV-Infected Patients

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Apr 26

PMID 27111769

Citations 22

Authors

Mar Masia

Sergio Padilla

Marta Fernandez

Carmen Rodriguez

Ana Moreno

Jose A Oteo

Antonio Antela

Santiago Moreno

Julia Del Amo

Felix Gutierrez

Affiliations

Soon will be listed here.

Abstract

Objective: We aimed to assess whether oxidative stress is a predictor of mortality in HIV-infected patients.

Methods: We conducted a nested case-control study in CoRIS, a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naïve at entry, launched in 2004. Cases were patients who died with available stored plasma samples collected. Two age and sex-matched controls for each case were selected. We measured F2-isoprostanes (F2-IsoPs) and malondialdehyde (MDA) plasma levels in the first blood sample obtained after cohort engagement.

Results: 54 cases and 93 controls were included. Median F2-IsoPs and MDA levels were significantly higher in cases than in controls. When adjustment was performed for age, HIV-transmission category, CD4 cell count and HIV viral load at cohort entry, and subclinical inflammation measured with highly-sensitive C-reactive protein (hsCRP), the association of F2-IsoPs with mortality remained significant (adjusted OR per 1 log10 increase, 2.34 [1.23-4.47], P = 0.009). The association of MDA with mortality was attenuated after adjustment: adjusted OR (95% CI) per 1 log10 increase, 2.05 [0.91-4.59], P = 0.080. Median hsCRP was also higher in cases, and it also proved to be an independent predictor of mortality in the adjusted analysis: OR (95% CI) per 1 log10 increase, 1.39 (1.01-1.91), P = 0.043; and OR (95% CI) per 1 log10 increase, 1.46 (1.07-1.99), P = 0.014, respectively, when adjustment included F2-IsoPs and MDA.

Conclusion: Oxidative stress is a predictor of all-cause mortality in HIV-infected patients. For plasma F2-IsoPs, this association is independent of HIV-related factors and subclinical inflammation.

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References

Steinberg D, Parthasarathy S, Carew T, Khoo J, Witztum J . Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989; 320(14):915-24. DOI: 10.1056/NEJM198904063201407. View

Hulgan T, Morrow J, DAquila R, Raffanti S, Morgan M, Rebeiro P . Oxidant stress is increased during treatment of human immunodeficiency virus infection. Clin Infect Dis. 2003; 37(12):1711-7. DOI: 10.1086/379776. View

Grotto D, Santa Maria L, Boeira S, Valentini J, Charao M, Moro A . Rapid quantification of malondialdehyde in plasma by high performance liquid chromatography-visible detection. J Pharm Biomed Anal. 2006; 43(2):619-24. DOI: 10.1016/j.jpba.2006.07.030. View

Tang A, Smit E . Oxidative stress in HIV-1-infected injection drug users. J Acquir Immune Defic Syndr. 2000; 25 Suppl 1:S12-8. DOI: 10.1097/00042560-200010001-00003. View

Sobrino-Vegas P, Gutierrez F, Berenguer J, Labarga P, Garcia F, Alejos-Ferreras B . [The Cohort of the Spanish HIV Research Network (CoRIS) and its associated biobank; organizational issues, main findings and losses to follow-up]. Enferm Infecc Microbiol Clin. 2011; 29(9):645-53. DOI: 10.1016/j.eimc.2011.06.002. View

Steiner J, Haughey N, Li W, Venkatesan A, Anderson C, Reid R . Oxidative stress and therapeutic approaches in HIV dementia. Antioxid Redox Signal. 2006; 8(11-12):2089-100. DOI: 10.1089/ars.2006.8.2089. View

Ingle S, May M, Gill M, Mugavero M, Lewden C, Abgrall S . Impact of risk factors for specific causes of death in the first and subsequent years of antiretroviral therapy among HIV-infected patients. Clin Infect Dis. 2014; 59(2):287-97. PMC: 4073781. DOI: 10.1093/cid/ciu261. View

Nielsen F, Mikkelsen B, Nielsen J, Andersen H, Grandjean P . Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin Chem. 1997; 43(7):1209-14. View

Blanco J, Jarrin I, Martinez A, Siles E, Larrayoz I, Canuelo A . Shorter telomere length predicts poorer immunological recovery in virologically suppressed HIV-1-infected patients treated with combined antiretroviral therapy. J Acquir Immune Defic Syndr. 2014; 68(1):21-9. DOI: 10.1097/QAI.0000000000000398. View

10.

McComsey G, Morrow J . Lipid oxidative markers are significantly increased in lipoatrophy but not in sustained asymptomatic hyperlactatemia. J Acquir Immune Defic Syndr. 2003; 34(1):45-9. DOI: 10.1097/00126334-200309010-00006. View

11.

Masia M, Padilla S, Alvarez D, Lopez J, Santos I, Soriano V . Risk, predictors, and mortality associated with non-AIDS events in newly diagnosed HIV-infected patients: role of antiretroviral therapy. AIDS. 2012; 27(2):181-9. DOI: 10.1097/QAD.0b013e32835a1156. View

12.

Sohal R, Orr W . The redox stress hypothesis of aging. Free Radic Biol Med. 2011; 52(3):539-555. PMC: 3267846. DOI: 10.1016/j.freeradbiomed.2011.10.445. View

13.

Sinha J, Ghosh S, Swain U, Giridharan N, Raghunath M . Increased macromolecular damage due to oxidative stress in the neocortex and hippocampus of WNIN/Ob, a novel rat model of premature aging. Neuroscience. 2014; 269:256-64. DOI: 10.1016/j.neuroscience.2014.03.040. View

14.

Banerjee A, Zhang X, Manda K, Banks W, Ercal N . HIV proteins (gp120 and Tat) and methamphetamine in oxidative stress-induced damage in the brain: potential role of the thiol antioxidant N-acetylcysteine amide. Free Radic Biol Med. 2010; 48(10):1388-98. PMC: 2873898. DOI: 10.1016/j.freeradbiomed.2010.02.023. View

15.

Vassimon H, Deminice R, Machado A, Monteiro J, Jordao A . The association of lipodystrophy and oxidative stress biomarkers in HIV-infected men. Curr HIV Res. 2010; 8(5):364-9. DOI: 10.2174/157016210791330347. View

16.

Suresh D, Annam V, Pratibha K, Prasad B . Total antioxidant capacity--a novel early bio-chemical marker of oxidative stress in HIV infected individuals. J Biomed Sci. 2009; 16:61. PMC: 2714592. DOI: 10.1186/1423-0127-16-61. View

17.

Hernando V, Sobrino-Vegas P, Burriel M, Berenguer J, Navarro G, Santos I . Differences in the causes of death of HIV-positive patients in a cohort study by data sources and coding algorithms. AIDS. 2012; 26(14):1829-34. DOI: 10.1097/QAD.0b013e328352ada4. View

18.

Okoye A, Picker L . CD4(+) T-cell depletion in HIV infection: mechanisms of immunological failure. Immunol Rev. 2013; 254(1):54-64. PMC: 3729334. DOI: 10.1111/imr.12066. View

19.

Roest M, Voorbij H, van der Schouw Y, Peeters P, Teerlink T, Scheffer P . High levels of urinary F2-isoprostanes predict cardiovascular mortality in postmenopausal women. J Clin Lipidol. 2011; 2(4):298-303. DOI: 10.1016/j.jacl.2008.06.004. View

20.

Tien P, Choi A, Zolopa A, Benson C, Tracy R, Scherzer R . Inflammation and mortality in HIV-infected adults: analysis of the FRAM study cohort. J Acquir Immune Defic Syndr. 2010; 55(3):316-22. PMC: 2955817. DOI: 10.1097/QAI.0b013e3181e66216. View