A trial of the effect of micronutrient supplementation on treatment outcome, T cell counts, morbidity, and mortality in adults with pulmonary tuberculosis.

BACKGROUND: Tuberculosis (TB) often coincides with nutritional deficiencies. The effects of micronutrient supplementation on TB treatment outcomes, clinical complications, and mortality are uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of micronutrients (vitamins A, B complex, C, and E, as well as selenium) in Dar es Salaam, Tanzania. We enrolled 471 human immunodeficiency virus (HIV)-infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months. RESULTS: Micronutrients decreased the risk ofTB recurrence by 45% overall (95% confidence interval [CI], 7% to 67%; P = .02) and by 63% in HIV-infected patients (95% CI, 8% to 85%; P = .02). There were no significant effects on mortality overall; however, we noted a marginally significant 64% reduction of deaths in HIV-negative subjects (95% CI, -14% to 88%; P = .08). Supplementation increased CD3+ and CD4+ cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients. Micronutrients reduced the incidence of peripheral neuropathy by 57% (95% CI, 41% to 69%; P < .001), irrespective of HIV status. There were no significant effects on weight gain, body composition, anemia, or HIV load. CONCLUSIONS: Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania.

Effects of maternal vitamin supplements on malaria in children born to HIV-infected women.

Vitamin deficiencies are frequent in children suffering from malaria. The effects of maternal multivitamin supplementation on the risk of malaria in children are unknown. We examined the impact of providing multivitamins or vitamin A/beta-carotene supplements during pregnancy and lactation to HIV-infected women on their children's risk of malaria up to 2 years of age, in a randomized, placebo-controlled trial. Tanzanian women (N = 829) received one of four daily oral regimens during pregnancy and after delivery: 1) vitamins B, C, and E (multivitamins); 2) vitamin A and beta-carotene (VA/BC); 3) multivitamins including VA/BC; or 4) placebo. After 6 months of age, all children received 6-monthly oral vitamin A supplements irrespective of treatment arm. The incidence of childhood malaria was assessed through three-monthly blood smears and at monthly and interim clinic visits from birth to 24 months of age. Compared with placebo, multivitamins excluding VA/BC reduced the incidence of clinical malaria by 71% (95% CI = 11-91%; P = 0.02), whereas VA/BC alone resulted in a nonsignificant 63% reduction (95% CI = -4% to 87%; P = 0.06). Multivitamins including VA/BC significantly reduced the incidence of high parasitemia by 43% (95% CI = 2-67%; P = 0.04). The effects did not vary according to the children's HIV status. Supplementation of pregnant and lactating HIV-infected women with vitamins B, C, and E might be a useful, inexpensive intervention to decrease the burden of malaria in children born to HIV-infected women in sub-Saharan Africa.

Vitamin supplements, socioeconomic status, and morbidity events as predictors of wasting in HIV-infected women from Tanzania.

BACKGROUND: Wasting is a strong independent predictor of mortality in HIV-infected persons. Vitamin supplements delay the disease progression, but their effect on wasting is not known. Data are lacking on the risk factors for wasting in African HIV-infected persons. OBJECTIVES: The objectives were to examine the effect of vitamin supplements on wasting in HIV-infected women and to assess the effects of sociodemographic characteristics, morbidity events, and immunologic progression on the risk of wasting. DESIGN: HIV-infected women (n = 1078) from Tanzania were randomly assigned to receive 1 of 4 daily oral regimens: multivitamins (B complex, C, and E), vitamin A plus beta-carotene, multivitamins that included vitamin A plus beta-carotene, or placebo. The endpoints of the study included first episodes of a midupper arm circumference <22 cm or a body mass index (BMI; in kg/m2) <18 and the incidence of weight loss episodes during a median 5.3 y of follow-up. RESULTS: Multivitamins alone significantly reduced the risk of a first episode of a midupper arm circumference <22 cm (relative risk: 0.66; 95% CI: 0.47, 0.94; P = 0.02). In multivariate-adjusted Cox models, the woman's age, education level, and height were inversely related to the incidence of wasting. Episodes of diarrhea, nausea or vomiting, lower respiratory tract infections, oral ulcers, thrush, severe anemia, and low CD4+ cell counts were each significantly related to an increased risk of wasting. CONCLUSIONS: Vitamins C and E and the vitamin B complex have a protective effect on wasting in HIV-infected women. Prevention of diarrhea, severe respiratory tract infections, and anemia are likely to decrease the burden of wasting.

Anemia is an independent predictor of mortality and immunologic progression of disease among women with HIV in Tanzania.

OBJECTIVES: To examine the association of anemia with mortality and disease progression among a cohort of women with HIV in Dar es Salaam, Tanzania. METHODS: Time to all-cause death, AIDS-related death, and a 50% decrease in CD4 cell count among 1078 HIV-positive pregnant women enrolled in a clinical trial of vitamin supplementation from 1995-2003. RESULTS: Adjusted models showed that anemia was associated with an increased risk of all-cause mortality (relative hazard [RH]: 2.06, 95% CI: 1.52 to 2.79 for moderate anemia and RH: 3.19, 95% CI: 2.23 to 4.56 for severe anemia) and AIDS-related mortality (RH: 2.21, 95% CI: 1.53 to 3.19 for moderate anemia and RH: 3.47, 95% CI: 2.25 to 5.33 for severe anemia), independent of CD4 cell count, World Health Organization clinical stage, age, pregnancy, vitamin supplementation, and body mass index. Anemia was also associated with a more rapid decline in CD4 counts, measured as time to a 50% drop in CD4 cell count from baseline. Erythrocyte characteristics suggestive of iron deficiency were also associated with all-cause and AIDS-related death and a 50% decline in CD4 cell count. CONCLUSIONS: Anemia is an independent predictor of mortality and disease progression in this cohort. Screening for anemia, coupled with prevention and treatment efforts, should be included in HIV care initiatives, particularly those that target women.

Multivitamin supplementation of HIV-positive women during pregnancy reduces hypertension.

Hypertension during pregnancy increases fetal growth retardation, preterm deliveries, and perinatal deaths, and yet its causes remain unclear. In HIV-infected women, preterm birth additionally increases the risk of HIV transmission to the infant. Oxidative stress and endothelial cell dysfunction of the placenta have been implicated in the development of hypertension during pregnancy. Vitamin intake can reduce oxidative stress and improve endothelial function. We therefore evaluated the effect of multivitamin (20 mg thiamine, 20 mg riboflavin, 25 mg B-6, 50 microg B-12, 500 mg C, 30 mg E, and 0.8 mg folic acid) and vitamin A supplements (30 mg beta-carotene plus 5000 IU preformed vitamin A) in relation to hypertension during pregnancy (systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg at any time during pregnancy). In a double-blind, placebo-controlled, randomized, clinical trial, conducted among 1078 HIV-positive pregnant Tanzanian women, those who received multivitamins were 38% less likely to develop hypertension during pregnancy than those who did not [relative risk (RR) = 0.62, 95% CI 0.40-0.94, P = 0.03]. There was no overall effect of vitamin A on hypertension during pregnancy (RR = 1.00, 95% CI 0.66-1.51, P = 0.98). Hypertension during pregnancy was more likely in women with high baseline systolic blood pressure (>120 vs. < or = 120 mm Hg) (RR = 6.02, 95%CI 2.59-13.97, P < 0.001), and those with higher mid-upper arm circumference (RR = 1.12, 95% CI 1.04-1.19, P = 0.002). Taking multivitamins containing vitamins B, C, and E during pregnancy may be an inexpensive and effective strategy to improve the health of the mother and baby.

Vitamin supplementation of HIV-infected women improves postnatal child growth.

BACKGROUND: Linear growth retardation and wasting are common in children born to HIV-infected women. Inexpensive interventions that could improve the postnatal growth pattern of such children are needed. OBJECTIVE: The objective was to examine the effect of supplementing HIV-infected women with multivitamins or vitamin A and beta-carotene, during and after pregnancy, on the growth of their children during the first 2 y of life. DESIGN: We conducted a randomized placebo-controlled trial in 886 mother-infant pairs in Tanzania. At the first prenatal visit, HIV-infected women were randomly assigned to 1 of 4 daily oral regimens in a 2 x 2 factorial fashion: multivitamins (MV: thiamine, riboflavin, vitamin B-6, niacin, vitamin B-12, vitamin C, vitamin E, and folic acid), preformed vitamin A + beta-carotene (VA/BC), MV including VA/BC, or placebo. Supplementation continued during the first 2 y postpartum and thereafter. Children were weighed and measured monthly, and all received vitamin A supplements after 6 mo of age per the standard of care. RESULTS: Multivitamins had a significant positive effect on attained weight (459 g; 95% CI: 35, 882; P = 0.03) and on weight-for-age (0.42; 95% CI: 0.07, 0.77; P = 0.02) and weight-for-length (0.38; 95% CI: 0.07, 0.68; P = 0.01) z scores at 24 mo. VA/BC seemed to reduce the benefits of MV on these outcomes. No significant effects were observed on length, midupper arm circumference, or head circumference. CONCLUSION: Supplementation of HIV-infected women with multivitamins (vitamin B complex, vitamin C, and vitamin E) during pregnancy and lactation is an effective intervention for improving ponderal growth in children.