DIETARY SUPPLEMENTATION's EFFECT ON HIV PROGRESSION

DIETARY SUPPLEMENTATION's EFFECT ON HIV PROGRESSION is the aim of a proposed 10,000-participant trial announced by Julie Buring, MD, Brigham and Women's Hospital, at the Nov. 10 Conference on Oxidative Stress in HIV/AIDS, held in Bethesda, Md. The proposed trial is intended to "evaluate the effects of nutritional supplementation with a number of agents such as vitamin E, C, B[6], B[12], beta carotene and/or zinc alone and in combination on AIDS progression among asymptomatic, HIV-positive individuals," Buring explained. A randomized, double-blind clinical trial, Buring's proposed study would be conducted entirely by mail, with an introductory letter sent to eligible participants explaining the trial's 2 factorial design and objectives. According to Buring, progression to disease is targeted as the trial's endpoint, rather than mortality. In an attempt to determine compliance, three months of "recognizant" pills (not the active agent) will be given to willing participants. At the end of the period, people taking the pills at least two-thirds of the time will then be randomized for treatment. Patients will be given monthly calendar pill packs with appropriate dosage marked per day, which, Buring stated, "helps with compliance, especially for asymptomatic participants." A follow-up questionnaire will be sent every six months "asking about compliance of the regimen, relevant medical outcomes and the use of other medications and side effects," Buring noted. Instead of receiving placebo, the control group for each agent will be given, in the form of a multivitamin, the Recommended Dietary Allowance (RDA) of the agents involved. According to Buring, the participants will be divided into 128 groups of equal size, with all groups receiving multivitamins, and 127 receiving one or more single vitamin supplements. Commenting on the statistical power of the trial, Buring noted that "any one of these six agents is being tested at an adequate power to detect a 20% benefit . . . for each agent alone," adding that "in combination, we begin to get to the point that what we could do is suggest that two agents are better than one, or three, or all the antioxidants are better than the B vitamins." Buring also stressed the importance of such a large sample size to legitimately detect an advantageous result from the many possible combinations. The funding sources for the study have not yet been defined. Although the National Institutes of Health has expressed interest in the trial, Buring noted that NIH is "richer on interest than [it is] on money." She added, however, that the trial organizers are "working with AmFAR [the American Foundation for AIDS Research] and trying to get [support] from a number of different directions." The estimated yearly cost of the trial is $ 800,000 -- $ 80 per participant. The proposed trial drew strong support from conference chairman Howard Greenspan, MD, LGD Biomedical Group. Referring to the trial's design as "wonderful," Greenspan stated at a press session following the conference that "it's the kind of trial that really needs to be done to . . . start understanding the effects of [vitamin] supplementation" on HIV progression. Although Greenspan acknowledged that the overall cost is high and a funding commitment is difficult to obtain, he declared: "Nevertheless, I don't think it's out of the realm of possibility . . . and in the interim maybe we look at other smaller trials -- other doctors are doing 150-patient trials or 200-patient trials with beta carotene or with vitamin E." He suggested that investigators look at [the nutrients] individually [to see] if any one [agent] has some effect [but] still continue looking at the combination." "I really do believe," Greenspan continued, "that it's a combination of therapies that is going to make a difference because the therapies are synergistic, but [regardless], they're all therapies aimed at returning oxidative balance to HIV- infected patients." In a related conference presentation, Gregg Coodley, Oregon Health Science University, reported the results of a double-blind, placebo-controlled trial "designed to test the efficacy of beta carotene in raising CD4 counts in HIV-infected patients." According to Coodley, 21 randomized, HIV-seropositive patients (20 men and one woman) were given either 180 mg of beta carotene or placebo daily for four weeks, followed by the reverse treatment for the next four weeks. Data demonstrated that the "absolute CD4 count, absolute CD4/CD8 ratio, total and B-lymphocytes all increased on [beta] carotene and fell during placebo," although the "differences did not reach statistical significance," according to an abstract. During his address, Coodley noted the controversy surrounding the question of whether the benefit obtained from beta carotene is through "a retinoid (vitamin A) or an alternative mechanism." Based on his study results, Coodley maintained that beta carotene has "an independent effect from vitamin A." However, he also suggested the need for further study in this area. Also at the conference, Herbert Pierson, MS/PhD, Preventive Nutrition Consultants, Inc., expounded the value of licorice root and garlic as antioxidant-containing "designer foods" against HIV. Using the results of past studies as evidence, Pierson stated that some of the phytochemicals in licorice root extract (i.e., triterpenoids, isoflavones, chalcones, flavonoids and acetophenomes) and garlic extract (i.e., S-allyl cysteine, diallyl disulfide, F4 protein, gamma-glutamyl alkenyl cysteines, fructans and vinyl dithiins) "help inhibit the virus; some help restore lost cellular functions; some possess direct antioxidant activity; and others stimulate endogenous antioxidant defenses and immunity."