To the Editor: Fawzi and coworkers (July 1 issue)1 demonstratethe benefit of multivitamin supplementation in pregnant womenwith human immunodeficiency virus (HIV) infection. What is mostimpressive is that the effects of vitamins on the immune system,on disease progression, and on mortality appear to be secondaryto immune-system restoration. Overwhelming but exhausted cellularimmune activation, characterized by activated T cells that areprone to apoptosis, and impairment of the ability of the immunesystem to restrict the growth of secondary pathogens are keyfeatures in the pathogenesis of HIV infection.2 Excessive productionof reactive oxygen species by activated cells such as macrophagesmay degrade vitamins, which are often effective antioxidants.3Accelerated conversion of tryptophan by the enzyme indolamine-2,3-dioxygenasehas been demonstrated in HIV infection.4 Indolamine-2,3-dioxygenasemay underlie diminished T-cell responsiveness in HIV infection.5This enzyme requires superoxide anion,5 which is destroyed byantioxidants. Thus, vitamin supplementation may compensate forthe enhanced degradation of vitamins and thereby counteractthe immunosuppression induced by indolamine-2,3-dioxygenaseand interrupt a vicious cycle. Regardless of these possibleexplanations, larger clinical trials will be needed to confirmthe 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{at}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. [Free Full Text]
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. [CrossRef][Medline]
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. [CrossRef][ISI][Medline]
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. [CrossRef][ISI][Medline]
Murray MF. Tryptophan depletion and HIV infection: a metabolic link to pathogenesis. Lancet Infect Dis 2003;3:644-652. [CrossRef][Medline]
The authors reply: Dr. Schroecksnadel and colleagues proposea mechanism by which multivitamin supplementation could resultin delayed disease progression among HIV-infected persons. Theirhypothesis is supported by the findings of our trial, in whichsupplementation with vitamin B complex and vitamins C and E,as compared with placebo, resulted in significantly increasedCD4+ cell counts and decreased risks of the HIV-related complicationsthat are common with immune suppression.
We agree that additional studies are needed to address the efficacyof various micronutrient supplements in the context of HIV infection.The trial in Tanzania, however, was not designed as a pilotstudy; it included a large sample and had adequate statisticalpower to detect an effect on clinical outcomes. Similar findingsin Thailand1 and the results of numerous epidemiologic studiesconfirm the importance of multivitamins in persons with HIVinfection.2 In light of the evidence accumulated to date, thenext trial involving persons in the early stages of HIV diseaseought to examine the role of other nutrients that were not includedin our regimen, such as selenium.3 The safety and efficacy ofvitamin and mineral supplementation among persons who have moreadvanced disease and who are receiving antiretroviral therapyare 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{at}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 PublicHealth 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. [Medline]
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. [ISI][Medline]
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