Nutritional deficiencies and the progression of hIV-positive individuals to AIDS.

An optimal nutritional status as well as adequate vitamin levels are known to be by themselves enough to prevent the development of AIDS in people who react positively on the tests for HIV (57-64).

For example, regarding vitamins in HIV disease progression and vertical transmission, researchers from the Harvard School of Public Health state: “The higher rates of HIV progression and vertical transmission in developing countries coincide with similarly higher rates of malnutrition and vitamin deficiencies, indicating that HIV infection, may be modified by nutritional status.” “Numerous observational studies report inverse association between vitamin status, measured bio-chemically or as levels of dietary intake, and the risk of disease progression or vertical transmission.” “Adequate vitamin status may also reduce vertical transmission through the intra-partum and breastfeeding routes by reducing HIV viral load in lower genital secretions and breast milk,” and “Vitamin supplements may be one of the few potential treatments that are inexpensive enough to be made available to HIV-infected persons in developing countries” (65).

Macronutrient (carbohydrates, proteins, fat, and fiber) deficiencies have been associated with low CD4 cell counts in HIV-positive individuals. HIV-positive individuals with low mean weight and low arm and muscle circumference (48,66) and HIV-positive children with growth impairment were shown to have low CD4 cell counts (48,67).

Wasting, particularly loss of lean body mass, is associated with early mortality (68,69) and susceptibility to opportunistic infections (48,69). In a case control study nested within a follow up study, HIV-positive IV drug users with wasting (more than 10% loss of weight from baseline to last visit before death; mean follow-up, 2.4 years) had an approximately 8 fold higher risk of mortality compared with controls, after adjusting for CD4 cell counts (48,55).

Higher mortality has been associated with low serum albumin (48,70). Low lean body mass index and high plasma levels of C-reactive proteins were also significant predictors of mortality among HIV-positive individuals followed for 42 months (48,71). Serum albumin and hemoglobin levels are also predictors of prognosis in HIV-positive children (48,72). Micronutrient deficiencies in HIV-positive individuals are associated with faster progression to AIDS (73).

A growing number of scientific trials implicate low serum vitamin A levels as a risk factor for HIV-positive individuals to progress into the clinical manifestations of AIDS (74-86).

“The risk of death among HIV-infected subjects with adequate serum vitamin A levels was 78% less, when compared with Vitamin A-deficient subjects” (65,78).

“In a study carried out among HIV-positive homosexual men, development of Vitamin A deficiency over an 18-month period was associated with a decline in CD4 cell count, widely used as a marker of HIV immune impairment. Normalization of vitamin A was associated with higher CD4 cell counts” (55,65).

“Lower serum levels of vitamin A were associated with a faster rate of progression among men who participated in the Multicenter AIDS Cohort Study (MACS)” (60,65).

In a nested case-control study, HIV-positive individuals with vitamin A deficiency had a fourfold higher risk of death than controls after adjusting for CD4 cell counts (48,55).

In a longitudinal study among HIV-positive IV drug users in Baltimore, low serum retinal levels were associated with a fourfold increase in risk for mortality after adjusting for CD4 cells counts (48,54).

In Rwanda higher likelihood of survival was noted among HIV-positive women with higher serum retinol levels (48,87).

On the other hand: “Among well nourished HIV seropositive men who participated in the San Francisco Men’s Health Study, high energy-adjusted vitamin A intake at baseline was associated with higher CD4 cell count at baseline, as well as with lower risk of developing AIDS during the 6 year period follow up” (62,65).

Development of vitamin A or B12 deficiency was significantly associated with a decline in CD4 cell count in a longitudinal study in HIV-positive gay men (48,88). In the same study, normalization of vitamin A, vitamin B12, and zinc was significantly associated with higher CD4 cell count, a finding that was not affected by the use of AZT.

In a randomized trial, daily supplementation with 180 mg of beta-carotene for 4 weeks was associated with a small increase in total white blood cell count, an increase in CD4 cell count, and a beneficial change in CD4/CD8 ratio compared with study participants receiving a placebo. These parameters decreased when participants in the beta-carotene arm were switched to the placebo arm (48,89).

Daily supplementation with selenium or beta-carotene for 1 year led to significant increases in glutathion peroxidase activity at 3 and 6 months among HIV-positive men and women in France (48,90).

In Thailand, HIV-positive pregnant women in the first trimester with CD4 counts less than 200 cells/cubic mm had mean serum vitamin A beta-carotene levels 37% lower than those in HIV-negative individuals (48,91).

In a longitudinal study in Miami, HIV-positive women with CD4 counts less than 200/cubic mm were more likely to have lower levels of plasma selenium and vitamin A an E than men with similar CD4 cell counts (48,92).

In a placebo-controlled trial in South Africa among children born to HIV-positive women, Vitamin A supplements resulted in approximately 50% reduction in diarrheal morbidity and progression to AIDS among HIV-positive children (65,77). Increased number of natural killer cells in HIV-infected children has also been observed following vitamin A supplementation in South Africa (48,93).

In addition to vitamin A, a growing number of studies show that “HIV-positive” individuals are at higher risk of deficiency of vitamins B1, B2, B6, B12, C, D, and E (65,94-101). Furthermore, deficiencies of B-complex vitamins, vitamin C, vitamin E and vitamin D increment the risk of progression of “HIV-positive” individuals to AIDS (65,94-101). For example, Vitamin B6 deficiency in “HIV-positive” individuals has been associated with reduced natural killer cell cytotoxicity and impaired mitogen-induced lymphocyte proliferation (102).

In a randomized, placebo-controlled, double-blind study in Canada, a significant reduction in viral load was achieved after 3 months of supplementation with large daily doses of vitamins C and E (48,103).

In the MACS study (104) and in a study in San Francisco (105), high levels of vitamin C, thiamin, or niacin intake were associated with a reduced risk of progression to AIDS (48).

Also in the MACS study, high dietary intake of vitamins B1, B2, B6, and niacin were associated with increased survival time of up to 1.3 years (48,106).

Increase intake of iron, vitamin E, and riboflavin significantly reduced the hazard for AIDS (48,105).

Lower vitamin E levels increased the risk of progression to AIDS (48,107). In the same study population, low serum vitamin B12 levels were associated with a twofold increase in the risk for progression (48,108).

Plasma zinc and magnesium levels were shown to be significant predictors of CD4 cell count among HIV-positive individuals in the United States (48,109).

In San Francisco, higher dietary intake of zinc, thiamine, niacin, and riboflavin were positively related to CD4 cell counts (48,105).

In a case-control study nested in the MACS study, patients who progressed to AIDS had significantly lower levels of serum zinc compared with nonprogressors and HIV-negative participants (48,110).

Selenium deficiency in HIV-positive individuals has been observed to increase risk of death among adults (48,111,112).