Log in

Dawn of antioxidants and immune modulators to stop HIV-progression and boost the immune system in HIV/AIDS patients: An updated comprehensive and critical review

  • Review article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

In the last two decades, human immunodeficiency virus (HIV), the retrovirus responsible for the acquired immunodeficiency syndrome (AIDS), is one of the leading causes of morbidity and mortality, worldwide. Providing the optimum management of HIV/AIDS is a major challenge in the 21st century. Since, HIV-infected persons have an extended lifespan due to the development of effective antiretroviral therapies, malnutrition is becoming central factors of long-term survivors. The nutrition status of AIDS patients has a significant influence on the maintenance and optimal effectiveness of the immune system. Micronutrient therapy in combination with allopathic treatments can extend and improve the quality and quantity of life in individuals infected with HIV/AIDS. HIV infection is thought to lead to augmented oxidative stress which may in turn lead to faster development of HIV disease. Hence, antioxidants might have a significant role in the treatment of HIV/AIDS. An additional approach to treating HIV infection is fortifying the immune response of infected people. Immune modulators help to activate and boost the normal immune function. The present review first describes the boon of antioxidants (especially Vitamin A) and immune modulators (cytolin, resveratrol, murabutide, setarud, tucaresol, AVR118, Immunitin (HE2000), reticulose, and interleukin-7) in the treatment of HIV/AIDS. Then, providing a comparatively succinct outline on updated patents study on antioxidants and immune modulators to treat HIV/AIDS will be discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Ramana LN, Anand AR, Sethuraman S, Krishnan U. Targeting strategies for delivery of anti-HIV drugs. J Control Release 2014;192:271–83.

    Article  CAS  PubMed  Google Scholar 

  2. Date AA, Destache CJ. A review of nanotechnological approaches for the prophylaxis of HIV/AIDS. Biomaterials 2013;34(26):6202–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Buckheit Jr RW, Watson KM, Morrow KM, Ham AS. Development of topical microbicides to prevent the sexual transmission of HIV. Antiviral Res 2010;85(1):142–58.

    Article  CAS  PubMed  Google Scholar 

  4. https://doi.org/www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2013/gr2013/UNAIDS_Global_Report_2013_en.pdfen/media/unaids/contentassets/documents/epidemiology/2013/gr2013/UNAIDS_Global_Report_2013_en.pdf [accessed 17.05.14].

  5. Hankins CA, Dybul MR. The promise of pre-exposure prophylaxis with antiretroviral drugs to prevent HIV transmission: a review. Curr Opin HIV AIDS 2013;8(1):50–8.

    Article  CAS  PubMed  Google Scholar 

  6. Jain VK, Chandra RK. Does nutritional deficiency predispose to acquired immune deficiency syndrome? Nutr Res 1984;4:537–43.

    Article  Google Scholar 

  7. Task Force on Nutrition Support in AIDS. Guidelines for nutrition support in AIDS. Nutrition 1989;5(1):39–46.

    Google Scholar 

  8. Tang AM, Smit E. Selected vitamins in HIV infection: a review. AIDS Patient Care STDS 1998;12(4):263–73.

    Article  CAS  PubMed  Google Scholar 

  9. Sepulveda RT, Watson RR. Treatment of antioxidant deficiencies in AIDS patients. Nutr Res 2002;22(1–2):27–37.

    Article  CAS  Google Scholar 

  10. Garland M, Fawzi WW. Antioxidants and progression of human immunodeficiency virus (HIV) disease. Nutr Res 1999;19(8):1259–76.

    Article  CAS  Google Scholar 

  11. Pace GW, Leaf CD. The role of oxidative stress in HIV disease. Free Radic Biol Med 1995;19(4):523–8.

    Article  CAS  PubMed  Google Scholar 

  12. Bendich A. Antioxidant nutrients and immune functions – introduction. Adv Exp Med Biol 1990;262:1–12.

    Article  CAS  PubMed  Google Scholar 

  13. Bendich A. Role of antioxidants in the maintenance of immune functions. In: Frei B, editor. Natural antioxidants in human health and disease. San Diego, CA: Academic Press; 1994. p. 447–67.

    Google Scholar 

  14. Singh G, Pai RS. Recent advances of resveratrol in nanostructured based delivery systems and in the management of HIV/AIDS. J Control Release 2014;194:178–88.

    Article  CAS  PubMed  Google Scholar 

  15. https://doi.org/aidsinfo.nih.gov/drugs/531/tucaresol/0/patientdrugs/531/tucaresol/0/patient [accessed 07.10.14].

  16. SeyedAlinaghi SA, Paydary K, Emamzadeh-Fard S, Mohraz M. Treatment with IMODTM as a novel immune modulator in HIV positive patients. J AIDS Clinic Res 2012;3:180. https://doi.org/10.4172/2155-6113.1000180.

  17. Kheirandish P, Mohraz M, Farzamnfar B, Abdollahi M, Shahhosseiny MH, Madani H, et al. Preclinical and phase 1 clinical safety of Setarud (IMOD), a novel immunomodulator. DARU J Pharm Sci 2009;17(3):148–56.

    Google Scholar 

  18. Mohraz M, Kheirandish P, Kazerooni PA, Davarpanah MA, Shahhosseiny MH, Mahdavian B, et al. A clinical trial on the efficacy of IMOD in AIDS patients. DARU J Pharm Sci 2009;17(4):277–84.

    CAS  Google Scholar 

  19. Jakopin Z. Murabutide revisited: a review of its pleiotropic biological effects. Curr Med Chem 2013;20(16):2068–79.

    Article  CAS  PubMed  Google Scholar 

  20. Jackson EM, Herbst-Kralovetz MM. Intranasal vaccination with murabutide enhances humoral and mucosal immune responses to a virus-like particle vaccine. PLoS ONE 2012;7(7):e41529. https://doi.org/10.1371/journal.pone.0041529.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Darcissac EC, Truong MJ, Dewulf J, Mouton Y, Capron A, Bahr GM. The synthetic immunomodulator murabutide controls human immunodeficiency virus type 1 replication at multiple levels in macrophages and dendritic cells. J Virol 2000;74(17):7794–802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. https://doi.org/www.cytodyn.com/drug-pipeline/cytolindrug-pipeline/cytolin [accessed 15.10.14].

  23. https://doi.org/www.cancer.gov/drugdictionary?cdrid=453546drugdictionary?cdrid=453546 [accessed 20.11.14].

  24. https://doi.org/www.drugbank.ca/drugs/DB04979drugs/DB04979 [accessed 20.11.14].

  25. https://doi.org/www.aidsmeds.com/archive/HE2000_1647.shtmlarchive/HE2000_1647.shtml [accessed 20.11.14].

  26. https://doi.org/mylocation.net/advr/july%2011%202000%20old%20drug%20new%20fight.htmadvr/july%2011%202000%20old%20drug%20new%20fight.htm [accessed 20.11.14].

  27. https://doi.org/www.bloodindex.org/immune_theraphy.phpimmune_theraphy.php [accessed 20.11.14].

  28. Mehta S, Fawzi W. Effects of vitamins, including vitamin A, on HIV/AIDS patients. Vitam Horm 2007;75:355–83.

    Article  CAS  PubMed  Google Scholar 

  29. Coodley GO, Nelson HD, Loveless MO, Folk C. Beta-carotene in HIV infection. J AIDS 1993;6(3):272–6.

    CAS  Google Scholar 

  30. Baum MK, Shor-Posner G, Bonveni P, Cassetti I, Mantero-Atienza E, et al. Influence of HIV on vitamin status and requirements. Ann N Y Acad Sci 1992;669:165–73.

    Article  CAS  PubMed  Google Scholar 

  31. liang B, Chung S, Araghiniknam M, Lane LC, Watson RR. Vitamins and immunomodulation in AIDS. Nutrition 1996;12(1):1–7.

    Article  PubMed  Google Scholar 

  32. Vaghefi SB, Castellon-Vogel EA. Nutrition and AIDS: an introductory chapter. In: Watson RR, editor. Nutrition and AIDS. CRC Press; 1994. p. 1.

  33. https://doi.org/www.nutraingredients.com/Research/The-role-of-nutrition-in-living-with-HIV-AIDSResearch/The-role-of-nutrition-in-living-with-HIV-AIDS [accessed 17.10.14].

  34. https://doi.org/www.aidsmeds.com/articles/multivitamin_slows_1667_24915.shtmlarticles/multivitamin_slows_1667_24915.shtml [accessed 07.13.14].

  35. Dreizen S. Nutrition and the immune response – a review. Int J Vitam Nutr Res 1979;49(2):220–8.

    CAS  PubMed  Google Scholar 

  36. https://doi.org/www.who.int/elena/titles/bbc/vitamina_hiv_adults/en/elena/titles/bbc/vitamina_hiv_adults/en/ [accessed 07.10.14].

  37. Irlam JH, Visser MM, Rollins NN, Siegfried N. Micronutrient supplementation in children and adults with HIV infection. Cochrane Database Syst Rev 2010;(12):CD003650. https://doi.org/10.1002/14651858.CD003650.

  38. Semba RD, Graham NM, Caiaffa WT, Margolick JB, Clement L, Vlahov D. Increased mortality associated with vitamin A deficiency during human immunodeficiency virus type 1 infection. Arch Intern Med 1993;153(18):2149–54.

    Article  CAS  PubMed  Google Scholar 

  39. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development.

  40. Corbeau P, Reynes J. Immune reconstitution under antiretroviral therapy: the new challenge in HIV-1 infection. Blood 2011;117(21):5582–90.

    Article  CAS  PubMed  Google Scholar 

  41. Levy Y. Immunotherapy in HIV infection; current and future challenges. Retrovirology 2010;7(Suppl. 1):I13. https://doi.org/10.1186/1742-4690-7-S1-I13.

  42. Bandera A, Gori A, Trabattoni D, et al. Positive immunomodulatory effects of tucaresol in HIV-infected patients: results from a phase I/II trial after 40 weeks of follow-up. In: Abstract presented at: 10th conference on retroviruses and opportunistic infections (CROI); 2003. Abstract 654.

  43. Gazzola L, Marchetti G, Bandera A, et al. Dynamics of T Cells Homeostasis Induced by Tucaresol. In: Abstract presented at: 11th conference on retroviruses and opportunistic infections (CROI); 2004. Abstract 523.

  44. Gori A, Trabattoni D, Bandera A, Saresella M, Marchetti G, Gazzola L, et al. Immunomodulation induced by tucaresol in HIV infection: results of a 16 week pilot Phase I/II trial. Antivir Ther 2004;9(4):603–14.

    CAS  PubMed  Google Scholar 

  45. Khorram Khorshid HR, Abdollahi M, Novitsky YA, Shahhosseiny MH, Sadeghi B, Madani H, et al. Studies on potential mutagenic and genotoxic activity of setarud. DARU J Pharm Sci 2008;16(4):223–8.

    Google Scholar 

  46. Paydary K, Emamzadeh-Fard S, Khorram Khorshid HR, Kamali K, SeyedAlinaghi S, Mohraz M. Safety and efficacy of Setarud (IMODTM) among people living with HIV/AIDS: a review. Recent Pat Antiinfect Drug Discov 2012;7(1):66–72.

    Article  CAS  PubMed  Google Scholar 

  47. Mohraz M, Sedaghat A, Seyed Alinaghi S, Asheri H, Mohammaddoust S, Gharibdoost F, et al. Post marketing surveillance on safety and efficacy of IMOD in Iranian patients with HIV/AIDS. Infect Disord Drug Targets 2013;13(1):71–4.

    Article  CAS  PubMed  Google Scholar 

  48. https://doi.org/www.cehd.org/resveratrol-research/resveratrol-a-possible-tool-fortreating-hiv/resveratrol-research/resveratrol-a-possible-tool-fortreating-hiv/ [accessed 17.10.14].

  49. Lin Z, Li J, Fang D. SIRT1 involvement in virus-mediated diseases. JSM Microbiol 2014;2(1):1006, https://doi.org/www.jscimedcentral.com/Microbiology/microbiology-2-1006.phpMicrobiology/microbiology-2-1006.php [accessed 20.10.14].

  50. Heredia A, Davis C, Redfield R. Synergistic inhibition of HIV-1 in activated and resting peripheral blood mononuclear cells, monocyte-derived macrophages, and selected drug-resistant isolates with nucleoside analogues combined with a natural product, resveratrol. J Acquir Immun Defic Syndr 2000;25(3):246–55.

    Article  CAS  Google Scholar 

  51. Clouser CL, Chauhan J, Bess MA, Oploo JLV, Zhou D, Dimick-Gray S, Mansky LM, Patterson SE. Anti-HIV-1 activity of resveratrol derivatives and synergistic inhibition of HIV-1 by the combination of resveratrol and decitabine. Bioorg Med Chem Lett 2012;22(21):6642–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Darcissac EC, Truong MJ, Dewulf J, Mouton Y, Capron A, Bahr GM. The synthetic immunomodulator murabutide controls human immunodeficiency virus type 1 replication at multiple levels in macrophages and dendritic cells. J Virol 2000;74(17):7794–802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. https://doi.org/www.cancer.gov/clinicaltrials/search/view?cdrid=616946&version=HealthProfessional&protocolsearchid=13485787clinicaltrials/search/view?cdrid=616946&version=HealthProfessional&protocolsearchid=13485787 [accessed 20.10.14].

  54. https://doi.org/www.businesswire.com/news/home/20040303005223/en/Hollis-Eden-Pharmaceuticals-Presents-Data-Molecular-Mechanism-Action#.VG16kTSUcSFnews/home/20040303005223/en/Hollis-Eden-Pharmaceuticals-Presents-Data-Molecular-Mechanism-Action#.VG16kTSUcSF [accessed 20.10.14].

  55. https://doi.org/www.aidsmeds.com/archive/HE2000_1647.shtmlarchive/HE2000_1647.shtml [accessed 20.10.14].

  56. https://doi.org/www.clinicaltrials.gov/ [accessed 20.10.14].

  57. https://doi.org/www.learnr.pro/content/31084-hiv-and-aids-basic-elements-and-priorities/255content/31084-hiv-and-aids-basic-elements-and-priorities/255 [accessed 20.10.14].

  58. https://doi.org/www.eurekalert.org/pub_releases/1999-02/AVRC-AFAV-250299.phppub_releases/1999-02/AVRC-AFAV-250299.php [accessed 20.10.14].

  59. https://doi.org/mylocation.net/advr/july%2011%202000%20old%20drug%20new%20fight.htmadvr/july%2011%202000%20old%20drug%20new%20fight.htm [accessed 20.10.14].

  60. Vandergeeten C, Fromentin R, DaFonseca S, Lawani MB, Sereti I, Lederman MM, Ramgopal M, Routy JP, Sékaly RP, Chomont N. Interleukin-7 promotes HIV persistence during antiretroviral therapy. Blood 2013;121(21):4321–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Thiébaut R, Drylewicz J, Prague M, Lacabaratz C, Beq S, Jarne A. Quantifying and predicting the effect of exogenous interleukin-7 on CD4+T cells in HIV-1 infection. PLoS Comput Biol 2014;10(5):e1003630. https://doi.org/10.1371/journal.pcbi.1003630.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Schein PS, Kalebic T. Suppression of HIV expression by organic thiophosphate US 5824664 A, 1998.

  63. Hirsch GP, Bayless RK. Treating aids and HIV infection with methionine, US 5292773 A, 1994

  64. Oge WD, Herzenberg LA. Treatment of diseases associated with cysteine deficiency, US 5607974 A, 1997.

  65. Saxena B, Rathnam P, Bomshteyn A. Anti-HIV-1 activity of betulinol derivatives. US 20060019934 A1, 2006.

  66. Goldberg DI, White RD, Wilson DM. Method of reducing or preventing toxicity associated with antiretroviral therapy by stimulation of the intracellular gluthatione level. EP 0572110 A2, 1993.

  67. Tsai HH, Hwang SM, Kung PC. Use of plant extracts for treatment of HIV, HCV and HBV infections. US 5837257 A, 1998.

  68. Redfield RR, Davis CE, Heredia JA. A hydroxylated stilbene that promotes dna synthesis in a virally-targeted cell such as resveratrol; a nucleoside analogue having antiviral activity such as dideoxyinosine. US 6479466 B1, 2002.

  69. Boojamra CG, Lin KY, Mackman RL, Markevitch DY, Petrakovsky OV, Ray AS, Zhang L. Nucleoside phosphonate conjugates as anti HIV agents. EP 1778251 B1, 2011.

  70. Chan CKL, Courchesne M, Halab L, Moinet C. Novel c-21-keto lupane derivatives preparation and use thereof. WO 2009082818 A1, 2009.

  71. Moinet C, Halab L, Liu B, Denis R, Poisson C, Nguyen-Ba P, Bubenik M, Turcotte N, Chan CKL. Novel 17 beta lupane derivatives. EP 2257567 A1, 2010.

  72. Kniskern PJ, Hagopian A, Burke P. Expression of fusion protein of HIV envelope and HBsAG. US 5130247 A, 1992.

  73. Chen J, Cloyd MW, Lee K, Paar D, Wang L.Methods and compositions involving thymidine phosphorylase as a marker for HIV infection, aids progression, and drug resistance. EP 1444521 A1, 2004.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Roopa S. Pai.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Singh, G., Pai, R.S. Dawn of antioxidants and immune modulators to stop HIV-progression and boost the immune system in HIV/AIDS patients: An updated comprehensive and critical review. Pharmacol. Rep 67, 600–605 (2015). https://doi.org/10.1016/j.pharep.2014.12.007

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.pharep.2014.12.007

Keywords

Navigation