Multivitamin Supplements and HIV Disease Progression
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《新英格兰医药杂志》
To the Editor: Fawzi and coworkers (July 1 issue)1 demonstrate the benefit of multivitamin supplementation in pregnant women with human immunodeficiency virus (HIV) infection. What is most impressive is that the effects of vitamins on the immune system, on disease progression, and on mortality appear to be secondary to immune-system restoration. Overwhelming but exhausted cellular immune activation, characterized by activated T cells that are prone to apoptosis, and impairment of the ability of the immune system to restrict the growth of secondary pathogens are key features in the pathogenesis of HIV infection.2 Excessive production of reactive oxygen species by activated cells such as macrophages may degrade vitamins, which are often effective antioxidants.3 Accelerated conversion of tryptophan by the enzyme indolamine-2,3-dioxygenase has been demonstrated in HIV infection.4 Indolamine-2,3-dioxygenase may underlie diminished T-cell responsiveness in HIV infection.5 This enzyme requires superoxide anion,5 which is destroyed by antioxidants. Thus, vitamin supplementation may compensate for the enhanced degradation of vitamins and thereby counteract the immunosuppression induced by indolamine-2,3-dioxygenase and interrupt a vicious cycle. Regardless of these possible explanations, larger clinical trials will be needed to confirm the effects seen in this pilot study.
Katharina Schroecksnadel, M.D.
Robert Zangerle, M.D.
Dietmar Fuchs, Ph.D.
Innsbruck Medical University
A-6020 Innsbruck, Austria
dietmar.fuchs@uibk.ac.at
References
Fawzi WW, Msamanga GI, Spiegelman D, et al. A randomized trial of multivitamin supplements and HIV disease progression and mortality. N Engl J Med 2004;351:23-32.
Kinter A, Arthos J, Cicala C, Fauci AS. Chemokines, cytokines and HIV: a complex network of interactions that influence HIV pathogenesis. Immunol Rev 2000;177:88-98.
Fuchs D, Jaeger M, Widner B, Wirleitner B, Artner-Dworzak E, Leblhuber F. Is hyperhomocysteinemia due to oxidative depletion of folate rather than insufficient dietary intake? Clin Chem Lab Med 2001;39:691-694.
Zangerle R, Widner B, Quirchmair G, Neurauter G, Sarcletti M, Fuchs D. Effective antiretroviral therapy reduces degradation of tryptophan in patients with HIV-1 infection. Clin Immunol 2002;104:242-247.
Murray MF. Tryptophan depletion and HIV infection: a metabolic link to pathogenesis. Lancet Infect Dis 2003;3:644-652.
The authors reply: Dr. Schroecksnadel and colleagues propose a mechanism by which multivitamin supplementation could result in delayed disease progression among HIV-infected persons. Their hypothesis is supported by the findings of our trial, in which supplementation with vitamin B complex and vitamins C and E, as compared with placebo, resulted in significantly increased CD4+ cell counts and decreased risks of the HIV-related complications that are common with immune suppression.
We agree that additional studies are needed to address the efficacy of various micronutrient supplements in the context of HIV infection. The trial in Tanzania, however, was not designed as a pilot study; it included a large sample and had adequate statistical power to detect an effect on clinical outcomes. Similar findings in Thailand1 and the results of numerous epidemiologic studies confirm the importance of multivitamins in persons with HIV infection.2 In light of the evidence accumulated to date, the next trial involving persons in the early stages of HIV disease ought to examine the role of other nutrients that were not included in our regimen, such as selenium.3 The safety and efficacy of vitamin and mineral supplementation among persons who have more advanced disease and who are receiving antiretroviral therapy are also important issues that will need to be examined.
Wafaie W. Fawzi, M.B., B.S., Dr.P.H.
Harvard School of Public Health
Boston, MA 02115
mina@hsph.harvard.edu
Gernard I. Msamanga, M.D., Sc.D.
Muhimbili University College of Health Sciences
Dar es Salaam, Tanzania
David J. Hunter, M.B., B.S., Sc.D.
Harvard School of Public Health
Boston, MA 02115
References
Jiamton S, Pepin J, Suttent R, et al. A randomized trial of the impact of multiple micronutrient supplementation on mortality among HIV-infected individuals living in Bangkok. AIDS 2003;17:2461-2469.
Fawzi WW. Micronutrients and human immunodeficiency virus type 1 disease progression among adults and children. Clin Infect Dis 2003;37:Suppl 2:S112-S116.
Baum MK, Shor-Posner G, Lai S, et al. High risk of HIV-related mortality is associated with selenium deficiency. J Acquir Immune Defic Syndr Hum Retrovirol 1997;15:370-374.
Katharina Schroecksnadel, M.D.
Robert Zangerle, M.D.
Dietmar Fuchs, Ph.D.
Innsbruck Medical University
A-6020 Innsbruck, Austria
dietmar.fuchs@uibk.ac.at
References
Fawzi WW, Msamanga GI, Spiegelman D, et al. A randomized trial of multivitamin supplements and HIV disease progression and mortality. N Engl J Med 2004;351:23-32.
Kinter A, Arthos J, Cicala C, Fauci AS. Chemokines, cytokines and HIV: a complex network of interactions that influence HIV pathogenesis. Immunol Rev 2000;177:88-98.
Fuchs D, Jaeger M, Widner B, Wirleitner B, Artner-Dworzak E, Leblhuber F. Is hyperhomocysteinemia due to oxidative depletion of folate rather than insufficient dietary intake? Clin Chem Lab Med 2001;39:691-694.
Zangerle R, Widner B, Quirchmair G, Neurauter G, Sarcletti M, Fuchs D. Effective antiretroviral therapy reduces degradation of tryptophan in patients with HIV-1 infection. Clin Immunol 2002;104:242-247.
Murray MF. Tryptophan depletion and HIV infection: a metabolic link to pathogenesis. Lancet Infect Dis 2003;3:644-652.
The authors reply: Dr. Schroecksnadel and colleagues propose a mechanism by which multivitamin supplementation could result in delayed disease progression among HIV-infected persons. Their hypothesis is supported by the findings of our trial, in which supplementation with vitamin B complex and vitamins C and E, as compared with placebo, resulted in significantly increased CD4+ cell counts and decreased risks of the HIV-related complications that are common with immune suppression.
We agree that additional studies are needed to address the efficacy of various micronutrient supplements in the context of HIV infection. The trial in Tanzania, however, was not designed as a pilot study; it included a large sample and had adequate statistical power to detect an effect on clinical outcomes. Similar findings in Thailand1 and the results of numerous epidemiologic studies confirm the importance of multivitamins in persons with HIV infection.2 In light of the evidence accumulated to date, the next trial involving persons in the early stages of HIV disease ought to examine the role of other nutrients that were not included in our regimen, such as selenium.3 The safety and efficacy of vitamin and mineral supplementation among persons who have more advanced disease and who are receiving antiretroviral therapy are also important issues that will need to be examined.
Wafaie W. Fawzi, M.B., B.S., Dr.P.H.
Harvard School of Public Health
Boston, MA 02115
mina@hsph.harvard.edu
Gernard I. Msamanga, M.D., Sc.D.
Muhimbili University College of Health Sciences
Dar es Salaam, Tanzania
David J. Hunter, M.B., B.S., Sc.D.
Harvard School of Public Health
Boston, MA 02115
References
Jiamton S, Pepin J, Suttent R, et al. A randomized trial of the impact of multiple micronutrient supplementation on mortality among HIV-infected individuals living in Bangkok. AIDS 2003;17:2461-2469.
Fawzi WW. Micronutrients and human immunodeficiency virus type 1 disease progression among adults and children. Clin Infect Dis 2003;37:Suppl 2:S112-S116.
Baum MK, Shor-Posner G, Lai S, et al. High risk of HIV-related mortality is associated with selenium deficiency. J Acquir Immune Defic Syndr Hum Retrovirol 1997;15:370-374.