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The following pages provide an overview of the most recent research and clinical studies about the health benefits of micronutrients in fighting AIDS. This collection of scientific facts proves that anyone who privately or publicly questions the health value of micronutrients does not serve YOUR health, or the health of the people, but rather the multi-billion dollar investment 'business with disease' based on patented pharmaceutical drugs.

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Effect of micronutrient supplementation on disease progression in asymptomatic, antiretroviral-naive, HIV-infected adults in Botswana: a randomized clinical trial.

Source: JAMA 2013; 310(20):2154-63. doi: 10.1001/jama.2013.280923.

Author: Baum MK, Campa A, Lai S, Sales Martinez S, Tsalaile L, Burns P, Farahani M, Li Y, van Widenfelt E, Page JB, Bussmann H, Fawzi WW, Moyo S, Makhema J, Thior I, Essex M, Marlink R.

Affiliation: Florida International University, R. Stempel College of Public Health and Social Work, Miami.

Abstract:

IMPORTANCE: Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive.

OBJECTIVE: To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive.

DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), selenium alone, or multivitamins with selenium vs placebo in a factorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009.

INTERVENTIONS: Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo.

MAIN OUTCOMES AND MEASURES: Reaching a CD4 cell count less than 200/μL until May 2008; after this date, reaching a CD4 cell count of 250/μL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study.

RESULTS: There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/μL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of combined outcomes for disease progression (CD4 cell count ≤250/μL, AIDS-defining conditions, or AIDS-related death, whichever occurred earlier [adjusted HR, 0.56; 95% CI, 0.33-0.95; P = .03; AER, 6.48/100 person-years; censoring rate, 0.90; 23 events]). There was no effect of supplementation on HIV viral load. Multivitamins alone and selenium supplementation alone were not statistically different from placebo for any end point. Reported adverse events were adjudicated as unlikely to be related to the intervention, and there were no notable differences in incidence of HIV-related and health-related events among study groups.

CONCLUSIONS AND RELEVANCE: In ART-naive HIV-infected adults, 24-month supplementation with a single supplement containing multivitamins and selenium was safe and significantly reduced the risk of immune decline and morbidity. Micronutrient supplementation may be effective when started in the early stages of HIV disease.

Effect of micronutrient supplementation on disease progression in asymptomatic, antiretroviral-naive, HIV-infected adults in Botswana: a randomized clinical trial.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24281460

Author: Baum MK, et al.

Affiliation: Florida International University, R. Stempel College of Public Health and Social Work, Miami.

Abstract: Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive. The objective of this study was to investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive. The study was a randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), selenium alone, or multivitamins with selenium vs placebo in a factorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/L who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009. The interventions were daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo. The main outcomes and measures were reaching a CD4 cell count less than 200/L until May 2008; after this date, reaching a CD4 cell count of 250/L or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study. There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/L or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of combined outcomes for disease progression (CD4 cell count 250/L, AIDS-defining conditions, or AIDS-related death, whichever occurred earlier [adjusted HR, 0.56; 95% CI, 0.33-0.95; P = .03; AER, 6.48/100 person-years; censoring rate, 0.90; 23 events]). There was no effect of supplementation on HIV viral load. Multivitamins alone and selenium supplementation alone were not statistically different from placebo for any end point. Reported adverse events were adjudicated as unlikely to be related to the intervention, and there were no notable differences in incidence of HIV-related and health-related events among study groups. Concluding, in ART-naive HIV-infected adults, 24-month supplementation with a single supplement containing multivitamins and selenium was safe and significantly reduced the risk of immune decline and morbidity. Micronutrient supplementation may be effective when started in the early stages of HIV disease.

AIDS and amino acids

A review of clinical trials with Arginine in HIV/AIDS

Arginine: Clinical Potential of a Semi-Essential Amino Acid

Source: Alternative Medicine Review 2002;7(6):512-522

Author: Jeremy Appleton

Affiliation: National College of Naturopathic Medicine; Director of Scientific Affairs, Cardinal Nutrition

Abstract: A review of  pilot and double–blind studies indicates that supplementation with arginine may benefit HIV/AIDS patients. The combination of glutamine, arginine, and hydroxymethylbutyrate (HMB) may prevent loss of lean body mass in individuals with AIDS cachexia. The weight gain in the supplemented group was predominately lean muscle mass, while the placebo group lost lean mass. In a pilot study conducted with 11 patients NK-cell cytotoxicity increased 18.9 lytic units, compared to +0.3 lytic units with placebo.

Arginine and omega-3 fatty acids

A randomized double-blind controlled study of 6 months of oral nutritional supplementation with arginine and 3 fatty acids in HIV-infected patients. The Swiss HIV Cohort Study

Source: AIDS 1998; 12(1):53-63

Author: Pichard C, Sudre Ph, Karsegard V, Yerly S et al.

Affiliation: Division of Nutrition, University Hospital, Geneva, Switzerland

Abstract: This study was conducted to evaluate the effects of an oral nutritional supplement enriched with two potentially immunostimulant compounds (arginine and Ω-3 fatty acids) on the changes in food intake, body composition, immune parameters and viraemia in HIV-infected outpatients. Therefore a six-month prospective randomized double-blind controlled study was done in a university hospital outpatient nutrition clinic. Included were 64 HIV-infected outpatients with CD4 lymphocyte count ≥ 100 106/l. All patients received a daily oral nutritional supplement (606 kcal supplemented with vitamins, trace elements and minerals). In addition, half of the patients were randomized to receive 7.4 g arginine plus 1.7 g Ω-3 fatty acids. Disease progression measured by AIDS-defining events, CD4 and CD8 lymphocyte counts, viremia*, tumor necrosis factor soluble receptors, nutritional status determined by anthropometric, bioelectrical impedance and dietetic assessment. 55 patients completed the protocol. Compliance with and tolerance of oral nutritional supplement during the 6-month period was excellent. In both groups of patients the following were found: total energy intake was transiently increased and then returned to baseline level; nitrogen/energy intake ratio was increased throughout the study; gain of body weight and fat mass were approximately 2 and 1 kg, respectively, over 6 months, and were similar in both groups. In addition, CD4 and CD8 lymphocyte counts, viremia, tumor necrosis factor soluble receptors remained statistically unchanged and were similar in both groups. Conclusions: Enrichment of an oral nutritive supplement with arginine and Ω-3 fatty acids did not improve immunological parameters. However, body weight increased in both groups.

* Viremia (UK: viraemia) is a medical condition where viruses enter the bloodstream and hence have access to the rest of the body.

Molecular mechanism of arginine in HIV infection

Arginine Methylation of the HIV-1 nucleocapsid Protein Results in its Diminished Function.

Source: AIDS, Volume 21(7)23 April 2007, p795-805

Author: Invernizzi Cédric,1,4 Xie Baode,1 Frankel Fernando,1,4 Feldhammer Matthew,1 Roy Bibhuti,1 Richard Stéphane,2,3,4,5 Wainberg Mark 1,4

Affiliation: McGill University AIDS Centre,1 Terry Fox Molecular Oncology Group,2 Bloomfield Centre for Research on Aging at the Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital,3 the Departments of Medicine, Oncology,4 McGill University, Montreal, Quebec, Canada 5

Abstract: Tat is known to be asymmetrically arginine dimethylated by protein arginine methyltransferase 6 (PRMT6) in its ARM. The study investigated whether NC could act as a substrate for this enzyme. The HIV-1 nucleocapsid protein (NC) is involved in transfer RNA lys 3 annealing to the primer binding site of viral genomic RNA by means of two basic regions that are similar to the N–terminal portion of the arginine-rich motif (ARM) of Tat. The study shows that NC is an in-vivo target of PRMT6, and arginine methylation of NC reduces RNA annealing and the initiation of reverse transcription. These findings may lead to ways of driving HIV-infected cells out of latency with drugs that inhibit PRMT6.

L-Arginine: a Therapeutic Option for AIDS/HIV Infection?

Source: Med Hypotheses 1992 Jul;38(3):236-9 (ISSN: 0306-9877)

Author: Wrightham MN; Cann AJ; Sewell HF

Affiliation: Department of Immunology, University Hospital, Queen's Medical Centre, Nottingham, UK.

Abstract: Levels of L-arginine have been shown to induce broad immune stimulation in vitro and in vivo, but do not increase HIV gene expression in vitro but do not increase HIV gene expression in vitro. These observations, together with the lack of toxicity of this agent, suggest a novel therapeutic approach to HIV disease.

A Pilot Study of the Safety and Efficacy of Supplemental Arginine to Enhance Immune Function in Persons with HIV/AIDS

Source: Nutrition, Volume 18, 7, Pages 688–690 (July 2002)

Author: Barbara Swanson,1,2,3 Joyce K. Keithley,1,2,3 Janice M. Zeller,1,2,3 Beverely E. Sha 1,2,3

Affiliation: Adult Health Nursing, Rush University College of Nursing, Chicago, Illinois, USA, 1 Department of Immunology/Microbiology, Rush University College of Medicine, Chicago, Illinois, USA, 2 Section of Infectious Diseases, Rush-Presbyterian- St. Luke’s Medical Center, Chicago, Illinois, USA 3

Abstract: A randomized, double-blind, placebo-controlled pilot study in an academic medical center—based infectious disease clinic, tested 11 clinically stable, HIV-infected adults who had been treated with highly active, antiretroviral therapy and had HIV plasma RNA levels of less than 10 000 copies/mL. None of the participants experienced any adverse clinical, virologic, or neuropsychologic events that necessitated withdrawal from the study. The arginine-supplemented group showed a mean natural killer cell cytotoxicity increase of 18.9 lytic units, whereas the placebo group showed an increase of 0.3 lytic units. Short-term arginine supplementation is safe for persons with HIV/AIDS.

AIDS and micronutrients

Molecular basis of inhibitory effects of vitamin C in HIV infection

NF-kappa B-independent Suppression of HIV Expression by Ascorbic Acid.

Source: AIDS Res Hum Retroviruses. 1997 Feb 10;13(3):235-9

Author: Harakeh S, Jariwalla RJ

Affiliation: Linus Pauling Institute of Science and Medicine, Palo Alto, Ca , USA

Abstract: Ascorbic acid (ascorbate or vitamin C) has been shown to suppress the induction of HIV in latently infected T lymphocytic cells following stimulation with a tumor promoter (PMA) and inflammatory cytokine (TNF-alpha). These results suggest that the molecular mechanism of HIV inhibition by ascorbate is not mediated via NF-kappa B inhibition, unlike that seen with other antioxidants.

Molecular mechanism of inhibitory effects of  vitamin C  on  HIV replication

Mechanistic Aspects of Ascorbate Inhibition of Human Immunodeficiency Virus.

Source: Chem. Bio Interact. 1994 Jun;91(2-3):207-15

Author: Harakeh S, Niedzwiecki A, Jariwalla RJ.

Affiliation: Linus Pauling Institute of Science and Medicine, Palo Alto, Ca , USA

Abstract: The study investigates the molecular basis of the inhibitory effect of ascorbate (vitamin C) on human immunodeficiency virus (HIV) expression in unstimulated chronically infected and reporter cell lines. These results, combined with previous observations on the suppression of HIV RT activity, are consistent with a mechanism of action in which ascorbate exerts a posttranslational inhibitory effect on HIV by causing impairment of enzymatic activity.

Ascorbate Effect on Cytokine Stimulation of HIV Production.

Source: Nutrition 1995 Sep-Oct;11(5 Suppl):684-7

Author: Harakeh S, Jariwalla RJ.

Affiliation: Linus Pauling Institute of Science and Medicine, Palo Alto, CA, USA

Abstract: Ascorbic acid (AA) suppresses the production of HIV in a latently infected T-lymphocytic cell line (ACH-2) following stimulation with the tumor promoter, PMA. To evaluate the effect of ascorbic acid on virus activation following treatment with inflammatory cytokine, the study tested tumor necrosis factor alpha (TNF-alpha) whose levels are elevated in patients with HIV/AIDS.

Role of vitamin C and sulfur- containing micronutrients in HIV

Comparative Study of the Anti-HIV Activities of Ascorbate and Thiol-Containing Reducing Agents in Chronically HIV-Infected Cells.

Source: Am J Clin Nutr. 1991 Dec;54(6 Suppl):1231S-1235S

Author: Harakeh S, Jariwalla RJ

Affiliation: Linus Pauling Institute of Science and Medicine, Palo Alto, Ca , USA

Abstract: To elucidate the action of vitamin C on pathogenic human retroviruses, the study  investigated and compared the effects of noncytoxic concentrations of ascorbic acid (AA), its calcium salt (Ca-ascorbate), and two thiol-based reducing agents [glutathione (GSH) and N-acetyl-L-cysteine (NAC)] against human immunodeficiency virus (HIV)-1 replication in chronically infected T lymphocytes. These results further support the potent antiviral activity of ascorbate and suggest its therapeutic value in controlling HIV infection in combination with thiols.

Vitamin C inhibits HIV replication in vitro

Suppression of Human Immunodeficiency Virus Replication by Ascorbate in Chronically and Acutely Infected Cells.

Source: Proc Natl Acad Sci U S A 1990 Sep;87(18):7245-9 (ISSN: 0027-8424)

Author: Harakeh S; Jariwalla RJ; Pauling L

Affiliation: Linus Pauling Institute of Science and Medicine, Palo Alto, CA, USA

Abstract: The action of ascorbate (vitamin C) on human immunodeficiency virus type 1 (HIV-1) has been studied and the etiological agent clinically associated with AIDS. There was a suppression of virus production and cell fusion in HIV-infected T-lymphocytic cell lines grown in the presence of nontoxic concentrations of ascorbate. In chronically infected cells expressing HIV at peak levels, ascorbate reduced the levels of extracellular reverse transcriptase (RT) activity (by greater than 99%) and of p24 antigen (by 90%) in the culture supernatant.

AIDS and micronutrients

N–Acetyl–Cysteine

N-acetylcysteine, Alpha-lipoic acid, L-glutamine, and L-carnitine.

Source: Alternative Medicine Review 2000; 5(4):290-305

Author: Patrick L.

Affiliation: Associate Editor, Alternative Medicine Review; Private Practice, Tucson, AZ

Abstract: The study discussed the use of L-carnitine and acetyl-L-carnitine in treating mitochondrial toxicity, both in muscle and nerve pathologies as a relevant in nutritional treatment of HIV, given the mitochondrial toxicity of nucleoside analog reverse transcriptase inhibitor therapy. The current use of highly active antiviral therapies, their toxicity, and significant failure rates have created the need for a more conservative reassessment of HIV treatment.

N-Acetylcysteine: Potential for AIDS Therapy

Source: Pharmacology 1993, 46:121-129

Author: Roederer M, Staal FJ, Ela SW, Herzenberg LA, Herzenberg LA.

Affiliation: Department of Genetics, Stanford University, Stanford, Calif., USA

Abstract: People infected with HIV suffer not only from an inflammatory stress but also from depleted glutathione levels have led to a general hypothesis that these two are causally related, and that treatment of AIDS should include thiol-replenishment therapy. In particular, inflammatory stimulations are dependent on intracellular thiol levels, as they are potentiated at low glutathione levels (oxidative stress) and inhibited at high glutathione levels. The study shows that N-acetylcysteine can inhibit inflammatory stimulations, including that of HIV replication. Since N-acetylcysteine can replenish depleted glutathione levels in vivo, the study suggests that it be used as an adjunct in the treatment of AIDS.

N-acetyl-cysteine and L-2-oxathiazolidine-4-carboxylic Acid Enhance Contact-Dependent Growth of HIV in Resting Peripheral Blood Mononuclear Cells (PBMC) in Vitro and Increase Recovery of HIV from Human-PBMC SCID Mice.

Source: AIDS 1997, 11(1), p 33-41

Author: Chen, Ping; Bauer, Gerhard; Mitchell, James; Factor, Rachel; Markham, Richard; Schwartz, David H.

Affiliation: Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.

Abstract: The study evaluates the effects of N-acetyl-cysteine (NAC) and L-2-oxothiazolidine-4-carboxylic acid (OTC) on HIV replication in resting T lymphocytes mixed with chronically infected U1 promonocytic cells; examines the phenotypes of NAC- and OTC-treated cells; and monitors HIV recovery from hu-PBMC SCID mice. At concentrations ≤5 mM, NAC and OTC potentiate HIV growth in unstimulated PBMC in vitro and in SCID mice. Caution in the use of these agents as antiviral monotherapies is advisable.

Vitamin A deficiency in HIV infected women

Maternal Vitamin A Status and Mother-to-Child Transmission of HIV in West Africa.

Source: AIDS:Volume 14(7)5 May 2000p 908

Author: Castetbon, Katia ab; Manigart, Olivier c; Bonard, Dominique d; Thomas, Marie-Josee e; Dumon, Marie-France e; Malvy, Denis af; Perre, Philippe Van de c; Dabis, Francois

Affiliation: DITRAME Study Group

Abstract: Vitamin A deficit in HIV-infected women is multifactorial: intake reduction; impaired release of retinol binding protein (RBP); and excess urinary loss of retinol. These factors could act differently according to the background of endemic vitamin A deficit and the stage of HIV disease. Observations in different settings could therefore be useful to obtain a better understanding of the relationship between vitamin A and MTCT of HIV.

The Relationship Between Vitamin A and HIV Infection

Source: Pakistan J. Med. Res. Vol. 43 No.2, 2004

Author: Oguntibeju OO, Van Schalkywk FE & Van Den  Heever WMJ

Affiliation: School of Health Technology, Technikon Free State, P/Bag X20539, Bloemfontein 9300, South Africa

Abstract: Vitamin A may enhance (and their deficiency impair) the immune response in HIV-infected patients.  Of the micronutrients, the role of vitamin A in HIV infection has received prominent attention.  Although the total number of subjects in this study is relatively small, the data suggest an association between HIV infection and vitamin A and is consistent with deterioration of vitamin A status with advancing HIV infection.

Maternal Vitamin A Deficiency and Mother-to-Child Transmission of HIV-1

Source: Lancet 1994 Jun 25; 343(8913):1593-7

Author: Semba RD; Miotti PG; Chiphangwi JD; Saah AJ; Canner JK; Dallabetta GA; Hoover DR

Affiliation: Dana Center, Department of Immunology and Infectious Diseases, Baltimore, MD 21287-9019

Abstract: The study examined a vitamin A status in pregnant women as a risk factor for mother-to-child transmission of HIV in Malawi. Serum vitamin A, height, weight, CD4 T-cell counts, and duration of breastfeeding were measured in 338 HIV-positive mothers whose infant's HIV serostatus was known. The study suggests that maternal vitamin A deficiency contributes to mother-to-child transmission of HIV.

Vitamin A Deficiency and the Acute Phase Response Among HIV-1-Infected and -Uninfected Women in Kenya.

Source: Acquir Immune Defic Syndr 2002 Oct 1;31(2):243-9

Author: Baeten JM; McClelland RS; Richardson BA; Bankson DD; Lavreys L; Wener MH; Overbaugh J; Mandaliya K; Ndinya-Achola JO; Bwayo JJ; Kreiss JK

Affiliation: Department of Epidemiology, University of Washington, Seattle 98104-2499, USA. jbaeten@u.washington.edu.

Abstract: Vitamin A deficiency has been associated with faster disease progression and greater infectivity in observational studies. Serum levels increased significantly among women without an acute phase response, although not to normal levels among women who were deficient at baseline. Among HIV-1-infected individuals, it is likely that low serum vitamin A concentrations reflect more active infection and the acute phase response. These results provide possible explanations for the disparity between observational studies and randomized trials of vitamin A for HIV-1 infection.

The Effect of Antenatal Vitamin A and Beta-Carotene Supplementation on Gut Integrity of Infants of HIV-Infected South African Women.

Source: Pediatr Gastroenterol Nutr 2001 Apr;32(4):464-70

Author: Filteau SM; Rollins NC; Coutsoudis A; Sullivan KR; Willumsen JF; Tomkins AM

Affiliation: Centre for International Child Health, Institute of Child Health, London, United Kingdom. sfilteau@ich.ucl.ac.uk.

Abstract: Supplementation with vitamin A is important for protection against diarrhea, and may benefit gut function of infants of HIV-infected mothers. The study involved 238 infants of HIV-infected South African pregnant women. Vitamin A supplementation of HIV-infected pregnant women may prevent the deterioration in gut integrity in the subgroup of their infants who themselves become infected. Improving vitamin A status of HIV-infected infants may decrease their gastrointestinal morbidity.

The Effects of Vitamin A Supplementation on the Morbidity of Children Born to HIV-Infected Women.

Source: Am J Public Health. 1995 Aug;85(8 Pt 1):1049-51.

Author: Coutsoudis A, Bobat RA, Coovadia HM, Kuhn L, Tsai WY, Stein ZA.

Affiliation: Department of Paediatrics and Child Health, University of Natal, Durban, South Africa

Abstract: A randomized, placebo-controlled trial of vitamin A supplementation was carried out in 118 offspring of HIV-infected women in Durban, South Africa. The effects of vitamin A supplementation on morbidity of children born to human immunodeficiency virus (HIV)-infected women were evaluated in a population where vitamin A deficiency is not endemic. In a population not generally vitamin A deficient, vitamin A supplementation for children of HIV-infected women appeared to be beneficial, reducing morbidity. The benefit was observed particularly for diarrhea among HIV-infected children.

Effect of Multivitamin and Vitamin A Supplements on Weight Gain During Pregnancy Among HIV-1-Infected Women.

Source: Am J Clin Nutr. 2002, Nov;76(5):1082-90

Author: Villamor E, Msamanga G, Spiegelman D, Antelman G, Peterson KE, Hunter DJ, Fawzi WW.

Affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. evillamo@hsph.harvard.edu

Abstract: Multivitamin supplementation was shown to be effective in preventing adverse pregnancy outcomes among HIV-positive women. These protective effects could be mediated in part by an improvement in the pattern of gestational weight gain. Multivitamins including vitamin A were protective against low weight gain during the second trimester compared with multivitamins alone. Multivitamin supplementation during pregnancy improves the pattern of weight gain among HIV-infected women.

Infant Mortality and Maternal Vitamin A Deficiency During Human Immunodeficiency Virus Infection

Source: Clin Infect Dis 1995 Oct;21(4):966-72

Author: Semba RD; Miotti PG; Chiphangwi JD; Liomba G; Yang LP; Saah AJ; Dallabetta GA; Hoover DR

Affiliation: Department of Ophthalmology, Johns Hopkins Schools of Medicine and Hygiene and Public Health, Baltimore, Maryland, USA.

Abstract: The maternal factors that contribute to high mortality rates among infants born to women with human immunodeficiency virus (HIV) are unclear. The study followed 474 HIV-infected mothers and their infants in Malawi from pregnancy through the infants' 12th month of life. Maternal vitamin A deficiency during HIV infection may contribute to increased infant mortality.

Impact of Massive Dose of Vitamin A Given to Preschool Children with Acute Diarrhea on Subsequent Respiratory and Diarrhoeal Morbidity

Source: BMJ 1994 Nov 26;309(6966):1404-7

Author: Bhandari N; Bhan MK; Sazawal S

Affiliation: Department of Paediatrics, All India Institute of Medical Sciences, New Delhi.

Abstract: The impact of vitamin A supplementation on morbidity from acute respiratory tract infections and diarrhea in children aged 12-60 months. Double blind randomised placebo controlled field trial of 900 children from urban slum area in New Delhi, India. Results were consistent with a lack of impact on acute lower respiratory tract related mortality after vitamin A supplementation and a possible reduction in the severity of diarrhea.

Serum Vitamin A and Beta-Carotene Levels in Pregnant Women Infected with Human Immunodeficiency Virus-1.

Source: Obstetrics and Gynecology 1996 Apr; 87 (4); p. 564-7

Author: Phuapradit W; Chaturachinda K; Taneepanichskul S; Sirivarasry J; Khupulsup K; Lerdvuthisopon N

Affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Abstract: The study of 74 pregnant women seropositive for HIV-1 infection (17 with CD4 count below 200 cells/microliter) and 148 pregnant seronegative controls in the first trimester to determine if low levels of serum vitamin A and beta-carotene are present in pregnant women with human immunodeficiency virus-1 (HIV-1) infection. Compared with levels in uninfected women, serum vitamin A and beta-carotene are decreased in HIV-1-infected pregnant women in the first trimester with CD4 counts lower than 200 cells/microliter. These micronutrient concentrations also correlate with CD4 count.

Abnormal T–cell Subset Proportions in Vitamin–A–Deficient Children

Source: Lancet 1993 Jan 2; 341(8836):5-8

Author: Semba RD; Muhilal; Ward BJ; Griffin DE; Scott AL; Natadisastra G; West KP; Sommer A

Affiliation: Dana Center for Preventive Ophthalmology, Wilmer Institute, Baltimore, Maryland 21287-9019

Abstract: VitaminA supplementation can reduce childhood mortality from infectious diseases, the underlying biological mechanisms are largely unknown. The randomised, double-masked, placebo-controlled clinical trial of 55 children aged 3-6 years –30 with xerophthalmia and 25 without in West Java, Indonesia. Vitamin-A-deficient children have underlying immune abnormalities in T-cell subsets and these abnormalities are reversible with vitaminA supplementation.

A Randomized Trial of Vitamin A Supplements in Relation to Mortality Among Human Immunodeficiency Virus–Infected and Uninfected Children in Tanzania

Source: The Pediatric Infectious Disease Journal 1999; Volume: 18 (2); p. 127-33

Author: Fawzi WW; Mbise RL; Hertzmark E; Fataki MR; Herrera MG; Ndossi G; Spiegelman D

Affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. mina@hsph.harvard.edu

Abstract: Randomized, double blind, placebo-controlled trial. 687 children age 6 months to 5 years who were admitted to the hospital with pneumonia.Vitamin A deficiency, which is common among children in many developing countries, is particularly severe among HIV-infected children. Our findings indicate that vitamin A supplements, a low cost intervention, reduce mortality of HIV-infected children.

Relation of Vitamin A and Carotenoid Status to Growth Failure and Mortality Among Ugandan Infants with Human Immunodeficiency Virus.

Source: Nutrition 2001; VOL: 17 (7-8); p. 567-72

Author: Melikian G; Mmiro F; Ndugwa C; Perry R; Jackson JB; Garrett E; Tielsch J; Semba RD

Affiliation: Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Abstract: A longitudinal study of 194 HIV-infected infants in Kampala, Uganda. Plasma vitamin A, carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin), and vitamin E were measured at age 14 wk, and weight and height were followed up to age 12 months. These data suggest that low concentrations of plasma carotenoids are associated with increased risk of death during HIV infection among infants in Uganda.

Vitamin B-12 Abnormalities in HIV-Infected Patients

Source: European Journal of Haematology 1991 Jul;47(1):60-4

Author: Remacha AF; Riera A; Cadafalch J; Gimferrer E

Affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Abstract: A prospective study of 60 consecutively admitted patients with HIV infection was performed to document the prevalence, etiology and manifestations of low serum vitamin B-12 in such patients. Low serum B-12 levels were found in 10 patients (16.7%). low serum vitamin B-12 is often found in HIV-infected patients and it could be related to malabsorption, but clear megaloblastic abnormalities and treatment response could not be demonstrated. A decreased concentration of the serum binders due to disturbances in the leukocytes and related immunocompetent cell may play an additional role.

Vitamin B12 Malabsorption in Patients with Acquired Immunodeficiency Syndrome.

Source: Archives of Internal medicine 1989; 149 (9); p. 2039-41

Author: Harriman GR; Smith PD; Horne MK; Fox CH; Koenig S; Lack EE; Lane HC; Fauci AS

Affiliation: Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892

Abstract: The study examined 11 patients with the acquired immunodeficiency syndrome (AIDS) for evidence of subclinical vitamin B12 malabsorption. The study suggest that vitamin B12 malabsorption is common in patients with AIDS and may be a very early manifestation of infection with HIV-1.

Clinical Correlates of Subnormal Vitamin B12 Levels in Patients Infected with the Human Immunodeficiency Virus.

Source: American Journal of Hematology 1995; 49 (4); p. 318-22

Author: Paltiel O; Falutz J; Veilleux M; Rosenblatt DS; Gordon K

Affiliation: Department of Medicine, Montreal General Hospital, McGill University, Quebec, Canada

Abstract: The study determine the prevalence and describe the clinical correlates of subnormal cobalamin levels in subjects infected with the human immunodeficiency virus (HIV), and assesses its relationship to virus-mediated immunosuppression and/or anti-viral therapy. Decreased cobalamin levels are found frequently in HIV disease, especially among those treated with zidovudine. Evidence of B12 malabsorption is found among those with more advanced disease and gastrointestinal symptoms

Reversal of Apparent AIDS Dementia Complex Following Treatment with Vitamin B12.

Source: Journal of Internal Medicine 1993; 233 (6); p. 495-7

Author: Herzlich BC; Schiano TD

Affiliation: Department of Medicine, Maimonides Medical Center, Brooklyn, New York

Abstract: The human immunodeficiency virus (HIV)-associated dementia complex is characterized by difficulties in concentration and memory followed by apathy, social withdrawal and motor dysfunction. Decreased serum vitamin B12 levels occur in up to 20% of patients with AIDS and may adversely contribute to the haematologic and neurologic dysfunction which is frequently attributed to the human immunodeficiency virus. The AIDS dementia complex represented a reversible adverse synergistic interaction between the human immunodeficiency virus and vitamin B12 deficiency.

Abnormal Vitamin B12 Metabolism in Human Immunodeficiency Virus Infection. Association with Neurological Dysfunction.

Source: Archives of Neurology 1991; 48 (3); p. 312-4

Author: Kieburtz KD; Giang DW; Schiffer RB; Vakil N

Affiliation: Department of Neurology, University of Rochester, School of Medicine, NY 14642

Abstract: An increased prevalence of vitamin B12 deficiency has been reported in patients infected by the human immunodeficiency virus (HIV). The unexpectedly high prevalence (20%) of such abnormal vitamin B12 metabolism in a population of HIV-infected patients referred for neurological evaluation. Vitamin B12 deficiency may be a frequent and treatable cause of neurological dysfunction in patients with HIV infection.

Supplemental Multivitamins or Vitamin B Complex Significantly Delay Progression to AIDS and Death in South African Patients Infected with HIV.

Source: NLM Gateway, A service of the US National Institutes of Health
Conference on Retroviruses and Opportunistic Infections.

Author: Kanter AS, Spencer D, Steinberg M

Affiliation:

Abstract: A large retrospective, observational database containing detailed medical records on over 2100 HIV-positive patients spanning twelve years, who attended the Johannesburg General Hospital HIV Clinic. Encouraging result may represent a cost-effective treatment in HIV patient population and should be confirmed in a prospective, controlled study.

Vitamin Supplementation for Prevention of Mother-to-Child Transmission of HIV and Pre-term Delivery: a Systematic Review of Randomized Trial Including More than 2800 Women

Source: AIDS Research and Therapy 2005, 2(1):4

Author: Edward J Mills, Ping Wu, Dugald Seely, Gordon H. Guyatt

Affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada. millsej@mcmaster.ca

Abstract: Observational studies have suggested that low serum vitamin levels are associated with increased mother-to-child transmission (MTCT) of HIV and increased preterm delivery. The study determines the efficacy of vitamins on the prevention of MTCT and preterm delivery by systematically reviewing the available randomized controlled trials.

Supplemental Vitamin B and Progression to AIDS and Death in Black South African Patients Infected with HIV

Source: Journal Of Acquired Immune Deficiency Syndrome, 1999, Jul 1;21(3):252-3.

Author: Kanter A.S.,1 Spencer D.C.,2 Steinberg M.H.,3 Soltysik R,4 Yarnold P.R.,5 Graham N.M. 6

Affiliation: Wolfson College, University of Cambridge, Cambridge, U.K., 1 University of Witwatersrand School of Medicine, Johannesburg, South Africa, 2 HIV Management Services, Johannesburg, South Africa, 3 Intelligent Medical Objects, Chicago, Illinois, USA, 4 Northwestern University School of Medicine, Chicago, Illinois, USA, 5 Glaxo-Wellcome Inc., Research Triangle, North Carolina, USA 6

Abstract: A case control study of 175 pairs of Black HIV-positive patients. The median survival period for patients without vitamins was 144.8 weeks; for those who took vitamin B, 264.6 weeks (p = 0.0014). This demonstrates the vitamin's effect on both humoral and cellular immunity. The analyses demonstrate a positive relationship between therapeutic vitamin B use and delay of AIDS progression and death in Black HIV-positive patients in South Africa.

Effect of Multivitamin and Vitamin A Supplements on Weight Gain During Pregnancy Among HIV–1–Infected Women

Source: Am J Clin Nutr 2002 Nov;76(5):1082-90

Author: Villamor E; Msamanga G; Spiegelman D; Antelman G; Peterson KE; Hunter DJ; Fawzi WW

Affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. evillamo@hsph.harvard.edu.

Abstract: The study examined the effects of multivitamin and vitamin A supplements on weight gain during the second and third trimesters of pregnancy among HIV-infected women. The mean rate of weight gain was 306 g/wk during the second trimester and 247 g/wk during the third trimester. During the third trimester, average weight gain was significantly greater (by 304 g; 95% CI: 17, 590; P = 0.04) and the risk of low rate of weight gain (<or= 100 g/wk) was significantly lower (relative risk: 0.73; 95% CI: 0.58, 0.93) in women who received multivitamins than in women who did not..Multivitamins including vitamin A were protective against low weight gain during the second trimester compared with multivitamins alone.

Increased Uptake and Accumulation of Vitamin C in Human Immunodeficiency Virus 1-Infected Hematopoietic Cell Lines.

Source: J Biol Chem 1997 Feb 28;272(9):5814-20

Author: Rivas CI; Vera JC; Guaiquil VH; Velasquez FV; Borquez-Ojeda OA; Carcamo JG; Concha II; Golde DW

Affiliation: Program in Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

Abstract: The study analyzed vitamin C uptake and its effects on virus production and cellular proliferation in HIV-infected and uninfected human lymphoid, myeloid, and mononuclear phagocyte cell lines. Chronic or acute infection of these cell lines by HIV-1 led to increased expression of glucose transporter 1, associated with increased transport and accumulation of vitamin C. Infected cells also showed increased transport of glucose analogs. High concentrations of vitamin C were preferentially toxic to HIV-infected host defense cell lines in vitro.

Effects of Vitamin E and C Supplementation on Oxidative Stress and Viral Load in HIV-Infected Subjects

Source: AIDS 1998 Sep 10;12(13):1653-9

Author: Allard JP; Aghdassi E; Chau J; Tam C; Kovacs CM; Salit IE; Walmsley SL

Affiliation: Department of Medicine, University of Toronto, Ontario, Canada.

Abstract: A randomized placebo-controlled, double-blind study that assessed the effect of antioxidant vitamin supplementation on lipid peroxidation, a measure of oxidative stress, and viral load in humans. Forty-nine HIV-positive patients were randomized to receive supplements of both DL-alpha-tocopherol acetate (800 IU daily) and vitamin C (1000 mg daily), or matched placebo, for 3 months. Supplements of vitamin E and C reduce oxidative stress in HIV and produce a trend towards a reduction in viral load. This is worthy of larger clinical trials, especially in HIV-infected persons who cannot afford new combination therapies.

Nutritional Assessment of Vitamin E in Malnourished Patients with AIDS

Source: Nutrition 2000, Volume 16, Issue 5, pages 339–343

Author: Jacquline Pontes Monteiro,1,2,3,4 Daniel Ferreira da Cuhna,1,2,3,4 Selma Freire Carvalho Cunha,1,2,3,4 Vitorino Modesto dos Santos,1,2,3,4 Alceu A Jordao,1,2,3,4 Dalmo Correia,1,2,3,4 Mario Leon Silva–Vergara,1,2,3,4 Helio Vannucchi,1,2,3,4 Virmondes R. Junior,1,2,3,4 Maria Lourdes Pires Bianchi1,2,3,4

Affiliation: Nutrition Support Team, Medical School of Uberaba, Uberaba, Brazil, 1 Nutrition Division, Department of Internal Medicine, Medical School of Uberaba, Uberaba, Brazil, 2 Nutrition Division, University of São Paulo, São Paulo, Brazil, 3 Pharmaceutical Division, University of São Paulo, São Paulo, Brazil 4

Abstract: The aims of this study were to compare intake and serum levels of α-tocopherol between malnourished (MN) and non-malnourished (NMN) AIDS patients and to correlate α-tocopherol intake and serum levels. Undernutrition was defined as having a body mass index lower than 18.5 kg/m or a height–creatinine index lower than 70%. Vitamin E intake and serum levels did not show a significant correlation (r = −0.22, P > 0.05). Protein-energy nutrition status and acute-phase response were not factors determining vitamin status among AIDS patients.

Effects of Vitamin E and C Supplementation on Oxidative Stress and Viral Load in HIV-Infected Subjects

Source: AIDS 1998 Sep 10;12(13):1653-9

Author: Allard JP; Aghdassi E; Chau J; Tam C; Kovacs CM; Salit IE; Walmsley SL

Affiliation: Department of Medicine, University of Toronto, Ontario, Canada.

Abstract: A randomized placebo-controlled, double-blind study that involved 49 HIV-positive patients. They were randomized to receive supplements of both DL-alpha-tocopherol acetate (800 IU daily) and vitamin C (1000 mg daily), or matched placebo, for 3 months. The number of infections reported was nine in the vitamin group and seven in the placebo group. Supplements of vitamin E and C reduce oxidative stress in HIV and produce a trend towards a reduction in viral load. This is worthy of larger clinical trials, especially in HIV-infected persons who cannot afford new combination therapies.

A Randomized Trial of Multivitamin Supplements and HIV Disease Progression and Mortality.

Source: The New England Journal of Medicine, 2004;351(13):1367.

Author: Wafaie W. Fawzi, Dr.P.H., Gernard I. Msamanga, Donna Spiegelman, Ruilan Wei, Saidi Kapiga, Eduardo Villamor, Davis Mwakagile, Ferdinand Mugusi,., Ellen Hertzmark, Max Essex, and David J. Hunter

Affiliation: Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115

Abstract: The study of 1078 pregnant women infected with HIV in a double-blind, placebo-controlled trial in Dar es Salaam, Tanzania, to examine the effects of daily supplements of vitamin A (preformed vitamin A and beta carotene), multivitamins (vitamins B, C, and E), or both on progression of HIV disease, using survival models. The median follow-up with respect to survival was 71 months (interquartile range, 46 to 80). Multivitamin supplements delay the progression of HIV disease and provide an effective, low-cost means of delaying the initiation of antiretroviral therapy in HIV-infected women.

Studies of Vitamins and Minerals and HIV Transmission and Disease Progression

Source: American Society for Nutritional Sciences J. Nutr. 135:938-944, April 2005

Author: Wafaie Fawzi,1,2 Gernard Msamanga,4 Donna Spiegelman,2,3 and David J. Hunter1,2

Affiliation: Departments of Nutrition,1 Epidemiology,2 and Biostatistics,3 Harvard School of Public Health, Boston, MA, and Department of Community Health, Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania4

Abstract: The study shows the efficacy of multivitamin supplements in reducing adverse pregnancy outcomes and early childhood infections, and is currently provided to pregnant HIV-infected pregnant women in many programs. The efficacy of such supplements among HIV-negative pregnant women needs further study. Daily multivitamin supplements were found to reduce HIV disease progression among men and women in several observational studies and randomized trials, and to provide an important low-cost intervention that could be provided to adults in early stages of HIV disease to prolong the time before antiretroviral therapy is recommended.

Relation Among Micronutrient Intakes with CD4 Count in HIV Infected Patients

Source: Nutr Hosp. 2002 Nov-Dec;17(6):285-9.

Author: de Luis DA, Bachiller P, Aller R, de Luis J, Izaola O, Terroba MC, Cuellar L, González Sagrado M.

Affiliation: Sección de Endocrinología y Nutrición Clínica, Unidad de Apoyo a la Investigación, Hospital Río Hortega, Valladolid. dadluis@yahoo.es

Abstract: The aim of the study was to assess the correlation between micronutrients intakes and immune status in 119 HIV infected patients. In all patients the following parameters were assessed; age, sex, treatment with anti-retroviral drugs, performed an anthropometric evaluation (weight, tricipital skinfold, midarm circumference, and body mass index (BMI)) and a biochemical evaluation (glucose, albumin, prealbumin, transferrin, total proteins, limphocytes and count of CD4). Vitamin A, and D intakes were correlated with CD4 count, only vitamin D remained as a independent predictor parameter in a in multivariant model.

Micronutrients and HIV-1 Disease Progression.

Source: AIDS 1995, 9(9):1051-6

Author: Baum MK, Shor-Posner G, Lu Y, Rosner B, Sauberlich HE, Fletcher MA, Szapocznik J, Eisdorfer C, Buring JE, Hennekens CH.

Affiliation: Department of Epidemiology and Public Health, University of Miami School of Medicine, Florida 33101, USA.

Abstract: A longitudinal study that evaluated the relationship between plasma levels of nutrients and CD4 cell counts, along and in combination with beta 2-microglobulin (beta 2M; AIDS index) over an 18-month follow-up. Biochemical measurements of nutritional status including plasma proteins, zinc, iron and vitamins B1, B2, B6, B12 (cobalamin), A, E, C and folate and immunological markers [lymphocyte subpopulations (CD4) and beta 2M] were obtained in 108 HIV-1-seropositive homosexual men at baseline and over three 6-month time periods. The data suggest that micronutrient deficiencies are associated with HIV-1 disease progression and raise the possibility that normalization might increase symptom-free survival.

Vitamin Supplements May Delay AIDS

Source: Treatment Update. 1998 Apr;10(2):4-5

Author:

Affiliation:

Abstract: A South African study that shows that a multivitamin or B-vitamin complex supplement can delay the development of AIDS and prolong survival compared to not using such supplements. Doctors found that patients using multivitamins took twice as long to develop AIDS than those who did not take supplements, and patients using B-vitamin complex took five times as long

Antioxidant Vitamins and Immunodeficiency

Source: International Journal of Vitamin and Nutrition Research 1996;66(2):141-5

Author: Mastroiacovo P; Ajassa C; Berardelli G; Bruni R; Catania N; Fidanza A; Pace V; Zanzoglous S

Affiliation: Institute of General Physiology, La Sapienza University, Rome, Italy.

Abstract: The study of the plasma of 20 children from 1 to 6 years old with HIV infection. Vitamin assays (vitamin E and beta-carotene), hematochemical assays, and immunoassays were analyzed. The results indicate that in the seropositive children there is a state of hypovitaminosis involving the most important antioxidant vitamins.

AIDS and polyphenols

EGCG Inhibits Binding of HIV to Human T-cells

Source: Original Internist, March, 2004

Author: Luke Huber

Affiliation:

Abstract: The study finds EGCG inhibits the binding of HIV to human T-cells, the first step in HIV infection. The study is the first to describe this effect of the green tea catechin on the attachment of HIV to human T-cells.

Inhibitory effcts of EGCG on HIV replication

Polyphenolic antioxidant (-)-epigallocatechin-3-gallate from Green Tea as a Candidate anti-HIV agent.

Source: AIDS, 2002, Apr 12;16(6):939-41

Author: Fassina G, Buffa A, Benelli R, Varnier OE, Noonan DM, Albini A.

Affiliation: Instituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

Abstract: Epigallocatechin-3-gallate (EGCG), one of the components of green tea, has been suggested to have antiviral activity. EGCG strongly inhibited the replication of both virus strains as determined by reverse transcriptase and p24 assays on the cell supernatants.

Mechanistic aspects of EGCG in HIV

Epigallocatechin gallate, the Main Polyphenol in Green Tea, Binds to the T-cell Receptor, CD4: Potential for HIV-1 Therapy.

Source: J Allergy Clin Immunol. 2006 Dec;118(6):1369-74. Epub 2006 Oct 13

Author: Williamson MP, McCormick TG, Nance CL, Shearer WT.

Affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, United Kingdom

Abstract: The green tea flavonoid, epigallocatechin gallate (EGCG), has been proposed to have an anti-HIV-1 effect by preventing the binding of HIV-1 glycoprotein (gp) 120 to the CD4 molecule on T cells. The study demonstrates clear evidence of high-affinity binding of EGCG to the CD4 molecule with a Kd of approximately 10 nmol/L and inhibition of gp120 binding to human CD4+ T cells. Epigallocatechin gallate has potential use as adjunctive therapy in HIV-1 infection.

How can Epigallocatechin Gallate from Green Tea Prevent HIV-1 Infection? Mechanistic Insights from Computational Modeling and the Implication for Rational Design of Anti-HIV-1 Entry Inhibitors.

Source: J Phys Chem B. 2006 Feb 16;110(6):2910-7

Author: Hamza A, Zhan CG.

Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, Kentucky 40536, USA.

Abstract: Possible inhibitors preventing human immunodeficiency virus type 1 (HIV-1) entry into the cells are recognized as hopeful next-generation anti-HIV-1 drugs. The results reveal that EGCG binds with CD4 in such a way that the calculated binding affinity of gp120 with the CD4-EGCG complex is negligible. The results and insights provide a rational basis for future design of novel, more potent inhibitors to block gp120-CD4 binding.