A randomized trial of the impact of multiple micronutrient supplementation on mortality among HIV-infected individuals living in Bangkok. A trial of the effect of micronutrient supplementation on treatment outcome, T cell counts, morbidity, and mortality in adults with pulmonary tuberculosis. Micronutrient supplementation increases CD4 count in HIV-infected individuals on highly active antiretroviral therapy: a prospective, double-blinded, placebo-controlled trial. Micronutrient supplements and mortality of HIV-infected adults with pulmonary TB: a controlled clinical trial. Micronutrient supplementation in the AIDS diarrhoea-wasting syndrome in Zambia: a randomized controlled trial. A randomized controlled trial evaluating nutrition counseling with or without oral supplementation in malnourished HIV-infected patients. Daily multi-micronutrient supplementation during tuberculosis treatment increases weight and grip strength among HIV-uninfected but not HIV-infected patients in Mwanza, Tanzania. Oral supplements as adjunctive treatment to nutritional counseling in malnourished HIV-infected patients: randomized controlled trial. Effect of periodic vitamin A supplementation on mortality and morbidity of human immunodeficiency virus-infected children in Uganda: A controlled clinical trial. Effect of micronutrients and iron supplementation on hemoglobin, iron status, and plasma hepatitis C and HIV RNA levels in female injection drug users: a controlled clinical trial. Nutritional supplements combined with dietary counselling diminish whole body protein catabolism in HIV-infected patients. A randomized trial of vitamin A supplements in relation to mortality among human immunodeficiency virus-infected and uninfected children in Tanzania.
To examine the impact of high-dose multiple micronutrient supplementation on survival and disease progression among HIV-infected individuals in Thailand.
                Randomized placebo-controlled trial.
                Four-hundred and eighty-one HIV-infected men and women living in and around Bangkok with CD4 cell counts in the range 50 x 10(6)- 550 x 10(6)/l were randomized to receive micronutrients or placebo for a period of 48 weeks. Trial participants were examined clinically 12-weekly and tested for CD4 cell count 24-weekly. A subset were tested for HIV plasma viral load at 48 weeks.
                Seventy-nine (16%) trial participants were lost to follow-up and 23 (5%) died. The death rate was lower in the micronutrients arm with the mortality hazard ratios [95% confidence interval (CI)] of 0.53 (0.22-1.25; P = 0.1) overall and 0.37 (0.13-1.06; P = 0.052) and 0.26 (0.07-0.97; P = 0.03) among those with CD4 cell counts < 200 x 10(6)/l and < 100 x 10(6)/l respectively. There was no impact on CD4 cell count or plasma viral load.
                Multiple micronutrient supplementation may enhance the survival of HIV-infected individuals with CD4 cell counts < 200 x 10(6)/l. This could have important public health implications in the developing world where access to antiretrovirals remains poor. The clinical findings need to be reproduced in other settings and the mechanism, which appears to be independent of change in CD4 cell count, merits further investigation. Tuberculosis (TB) often coincides with nutritional deficiencies. The effects of micronutrient supplementation on TB treatment outcomes, clinical complications, and mortality are uncertain.
                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.
                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.
                Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania. To examine the immunologic, metabolic, and clinical effects of broad spectrum micronutrient supplementation in HIV-infected patients taking highly active antiretroviral therapy (HAART).
                A prospective, randomized, double-blinded, placebo-controlled trial.
                Forty HIV-infected patients taking a stavudine and/or didanosine-based HAART regimen were prospectively randomized to receive micronutrients or placebo twice daily for 12 weeks. Data were collected at 4-week intervals including immunologic, metabolic, and clinical measurements. The study examined the effect of micronutrient supplementation on immunologic parameters as the primary end point. The secondary end points were metabolic and clinical effects and distal symmetrical polyneuropathy.
                The mean absolute CD4 count increased by an average of 65 cells in the micronutrient group versus a 6-cell decline in the placebo group at 12 weeks (P = 0.029). The absolute CD4 count increased by an average of 24% in the micronutrient group versus a 0% change in the placebo group (P = 0.01). The mean HIV-1 RNA decreased in the micronutrient supplementation group, although not significantly. Neuropathy scores improved in the micronutrient group by 42% compared with a 33% improvement in the placebo arm. This difference did not reach statistical significance. Fasting serum glucose, insulin, and lipids were not adversely affected in the patients taking the micronutrients.
                Micronutrient supplementation can significantly improve CD4 cell count reconstitution in HIV-infected patients taking HAART. The micronutrient supplement tested was well tolerated and may hold promise as an adjuvant therapy in the treatment of HIV. Further investigation is warranted. Zomba and Blantyre, Malawi, Africa.
                To determine whether daily micronutrient supplementation reduces the mortality of human immunodeficiency virus (HIV) infected adults with pulmonary tuberculosis (TB).
                A randomised, controlled clinical trial of micronutrient supplementation for HIV-positive and HIV-negative adults with pulmonary TB. Participants were enrolled at the commencement of chemotherapy for sputum smear-positive pulmonary TB and followed up for 24 months.
                A total of 829 HIV-positive and 573 HIV-negative adults were enrolled. During follow-up, 328 HIV-positive and 17 HIV-negative participants died. The proportion of HIV-positive participants who died in the micronutrient and placebo groups was 38.7% and 40.4%, respectively (P = 0.49). Micronutrient supplementation did not reduce mortality (hazard ratio [HR] 0.93, 95%CI 0.75-1.15) among HIV-positive adults.
                Micronutrient supplementation at the doses used in this study does not reduce mortality in HIV-positive adults with pulmonary TB in Malawi. As HIV has spread through sub-Saharan Africa, persistent diarrhoea has emerged as a major problem in hospitals and in the community in severely affected areas. We have previously demonstrated that antiprotozoal therapy with albendazole reduces diarrhoea in AIDS patients in urban Zambia. This trial was designed to test the hypothesis that the clinical response to albendazole might be improved by oral micronutrient supplementation.
                Randomized, placebo-controlled trial.
                Home care service of Ndola Central Hospital, Zambia.
                HIV-seropositive patients with persistent diarrhoea.
                Patients were randomized to albendazole plus vitamins A, C and E, selenium and zinc orally or albendazole plus placebo, for 2 weeks.
                Time with diarrhoea following completion of treatment; mortality; adverse events.
                Serum vitamin A and E concentrations before treatment were powerful predictors of early mortality, but supplementation did not reduce time with diarrhoea or mortality during the first month, even after taking into account initial vitamin A or E concentrations, CD4 cell count or clinical markers of illness severity. Serum concentrations of vitamins A and E did not increase significantly in supplemented patients compared with those given placebo, and there were no changes in CD4 cell count or haematological parameters. No adverse events were detected except those attributable to underlying disease.
                Although micronutrient deficiency is predictive of early death in Zambian patients with the diarrhoea-wasting syndrome, short-term oral supplementation does not overcome it nor influence morbidity or mortality. To evaluate the effects of nutrition counseling with or without oral supplementation in malnourished patients infected with the human immunodeficiency virus (HIV).
                Randomized controlled trial.
                HIV-infected men (n=118) who were less than 90% of usual weight for height or who had lost more than 10% of body weight.
                Nutrition counseling alone (control group) vs nutrition counseling plus enteral supplementation (supplement group) for 6 weeks. All patients were instructed to consume a diet that exceeded estimated total energy expenditure by 960 kcal/day.
                Weight, skinfold thickness, fat-free mass, grip strength, quality of life, and cognitive function (Buschke test).
                Differences in baseline variables and outcomes were evaluated using analysis of variance or the Wilcoxon rank sum test.
                Ninety-nine men completed at least 4 weeks of treatment, 49 in the supplement group and 50 in the control group. Half the patients in each treatment group achieved at least 80% of their energy target. No differences in weight, skinfold thickness measurements, or quality of life were observed. Compared with the control group, the supplement group had larger increases in fat-free mass and grip strength, although the differences did not reach statistical significance.
                In the short term, nutrition counseling with or without oral supplementation can achieve a substantial increase in energy intake in about 50% of malnourished HIV-infected patients. Although further study is needed to evaluate long-term effects, these findings suggest that nutrition counseling has an important role in the management of malnourished HIV-infected patients. Undernutrition is common among tuberculosis (TB) patients. The objective of this study was to assess the effect of multi-micronutrient supplementation during TB treatment on weight, body composition, and handgrip strength. A total of 865 patients with smear-positive (PTB+) or -negative (PTB-) pulmonary TB were randomly allocated to receive a daily biscuit with or without multi-micronutrients for 60 d during the intensive phase of TB treatment. Weight, arm fat area, arm muscle area, and handgrip strength were assessed at baseline and after 2 and 5 mo. At 2 mo, the multi-micronutrient supplementation led to a higher handgrip gain (1.22 kg; 95% CI = 0.50, 1.94; P = 0.001) but had no effects on other outcomes. The effects of multi-micronutrient supplementation were modified by HIV infection (P-interaction = 0.002). Among HIV- patients, multi-micronutrient supplementation increased weight gain by 590 g (95% CI = -40, 1210; P = 0.07) and handgrip strength by 1.6 kg (95% CI = 0.78, 2.47; P < 0.001), whereas among HIV+ patients, it reduced weight gain by 1440 g (95% CI = 290, 2590; P = 0.002) and had no effect on handgrip strength (0.07 kg; 95% CI = -1.30, 1.46; P = 0.91). The reduced weight gain among HIV+ patients receiving multi-micronutrient supplementation seemed to be explained by a higher proportion of patients reporting fever. At 5 mo, the effects on weight were sustained, whereas there was no effect on handgrip strength. In conclusion, multi-micronutrient supplementation given as a biscuit is beneficial among HIV- PTB patients and may be recommended to TB programs. More research is needed to develop an effective supplement for HIV+ PTB patients. To compare nutritional counseling with and without oral supplements in HIV-infected patients with recent weight loss.
                Randomized non-blinded controlled trial, stratified for change in antiretroviral treatment at baseline.
                HIV-infected patients with recent weight loss (> 5% of total, and >3% in the last month).
                Nutritional counseling to increase dietary intake by 600 kcal/day over 8 weeks; in group A (n=24) by normal food, and in group B (n=26) by a range of fortified drink supplements with a calorific value of 0.6 to 1.5 kcal/ml.
                Body composition by bioelectrical impedance analysis, dietary intake by 24 h recall.
                Fat free mass increased from baseline to week 8 (P<0.05) with no difference between groups A and B (P=0.97). Body cell mass and weight gain were not significant and equal between groups. Assessed at weeks 2 and 4, group B patients consumed 11 +/- 6 kcal/kg as supplements, and their total energy intake was 6 kcal/kg higher than in group A (P<0.01). Total energy intake was not different between groups at weeks 6 and 8.
                Nutritional counseling and oral supplements are both feasible methods to restore food energy intake in malnourished HIV-infected patients. Although normal food intake is partially replaced, oral supplements may improve the adherence to a weight gain regimen.
                Copyright 1999 Harcourt Publishers Ltd. We investigated whether vitamin A supplementation would decrease mortality and morbidity rates in children infected with the human immunodeficiency virus (HIV).
                We conducted a randomized, double-blind, placebo-controlled clinical trial at Mulago Hospital, a large hospital that serves the urban and semiurban populations of Kampala, Uganda. One hundred eighty-one HIV-infected children were enrolled at 6 mo and randomized to receive vitamin A supplementation, 60 mg retinol equivalent, or placebo every 3 mo from ages 15 to 36 mo. Morbidity was assessed through a 7-d morbidity history every 3 mo, and vital events were measured. Children received daily trimethoprim-sulfamethoxazole prophylactic therapy.
                After age 15 mo, children were followed for a median of 17.8 mo (interquartile range = 11.1 to 21.0 mo). The trial was stopped when there was a new policy to implement a program of mass supplementation of vitamin A in the country. Mortality rates among 87 children in the vitamin A group and 94 children in the control group were 20.6% and 32.9%, respectively, yielding a relative risk of 0.54 (95% confidence interval, 0.30 to 0.98; P = 0.044) after adjusting for baseline weight-for-height Z score. Children who received vitamin A had lower modified point prevalences of persistent cough (odds ratio, 0.47; 95% confidence interval, 0.23 to 0.96; P = 0.038) and chronic diarrhea (odds ratio, 0.48; 95% confidence interval, 0.19 to 1.18; P = 0.11) and a shorter duration of ear discharge (P = 0.03). Vitamin A supplementation had no significant effect on modified point prevalences of fever, ear discharge, bloody stools, or hospitalizations.
                Vitamin A supplementation decreases mortality rate in HIV-infected children and should be considered in the care for these children in developing countries. Iron deficiency is common among female injection drug users, but it is unclear whether iron supplementation can reduce anemia and improve iron status without increasing plasma hepatitis C virus (HCV) or HIV RNA levels.
                We conducted a phase 3, double-blind, randomized, controlled clinical trial of daily micronutrients with 18 mg of iron (iron group) versus micronutrients without iron (control group) for 12 months among hepatitis C-positive female injection drug users in Baltimore, Maryland. The main outcome measures were hemoglobin, markers of iron status, plasma HCV RNA, plasma HIV RNA, and liver enzymes at 6 and 12 months of follow-up.
                Four hundred fifty-eight women (320 HIV-negative and 138 HIV-positive) enrolled in the trial. There were no significant differences in the proportion of women with anemia, ferritin<30 ng/mL, log10 plasma HCV RNA, or log10 plasma HIV RNA between treatment groups at enrollment. The proportion with anemia in the iron and control groups, respectively, was 20.7% versus 31.3% (P=0.026) at 6 months and 26.2% versus 30.4% (P=0.5) at 12 months; with ferritin<30 ng/mL, the proportion was 29.2% versus 55.5% (P<0.0001) at 6 months and 26.2% versus 46.9% (P=0.0018) at 12 months. In the iron and control groups, respectively, mean log10 plasma HCV RNA (IU/mL) was 5.2 versus 5.2 (P=0.86) at 6 months and 5.4 versus 5.3 (P=0.6) at 12 months. Among HIV-positive subjects, mean log10 plasma RNA (copies/mL) in the iron and placebo groups, respectively, was 3.8 versus 3.7 (P=0.75) at 6 months and 3.7 versus 4.1 (P=0.19) at 12 months. There were no significant differences in liver enzyme levels between the treatment groups at enrollment, 6 months, and 12 months.
                A daily micronutrient supplement with iron can reduce anemia and improve iron status in female injection drug users without increasing plasma HCV or HIV RNA levels or altering liver enzymes. Weight loss and protein malnutrition are frequent complications in HIV-infected patients. The effect of an oral nutritional supplement combined with nutritional counselling on whole body protein metabolism was assessed.
                HIV-infected individuals with a body mass index < 21 kg m-2 or CD4-T cells < 500 micro L-1 in stable clinical condition were randomly allocated to [1] receive either oral nutritional supplements (containing 2510 kJ, complete macro- and micronutrients) and dietary counselling (n = 8), or [2] identical monitoring but no supplements or specific nutritional advice (controls, n = 7). Whole body leucine kinetics and leucine oxidation rate were determined by [1-13C]-leucine infusions and lean and fat mass were measured before and 12 weeks after intervention.
                Leucine oxidation (protein catabolism) decreased in the group receiving nutritional intervention from 0.33 +/- 0.02 to 0.26 +/- 0.02 micromol kg-1 min-1 after 12 weeks (P < 0.05; P < 0.05 vs. control group) but remained unchanged in the control group. Whole body leucine flux showed a tendency to decrease in the intervention group from 1.92 +/- 0.19 to 1.73 +/- 0.14 micromol kg-1 min-1 (P = 0.07) and remained unchanged in the control group (2.21 +/- 0.16 and 2.27 +/- 0.14 micromol kg-1 min-1, respectively). Lean body mass determined by bioelectrical impedance analysis increased in the nutritional intervention group from 84 +/- 2 to 86 +/- 2 per cent (P < 0.05) and fat mass decreased from 17 +/- 2 to 14 +/- 2 per cent (P < 0.05) of total body weight whereas neither mass changed in the control group. Nutritional intervention had no significant effect on lymphocyte CD4 counts, on plasma TNFR 55, TNFR 75 and ILR 2 concentrations and on quality of life.
                The data demonstrate an anticatabolic effect of nutritional supplements combined with dietary counselling in HIV-infected subjects. They suggest that diminished whole body protein catabolism resulted in a change of body composition (increased lean mass, decreased fat mass). To determine whether vitamin A supplements result in reduced mortality among HIV-infected and uninfected children.
                Randomized, double blind, placebo-controlled trial.
                Starting in April, 1993, we randomized 687 children age 6 months to 5 years who were admitted to the hospital with pneumonia. Children who were severely malnourished or had clinical signs of vitamin A deficiency were excluded. At baseline children received placebo or 400 000 IU (or half that for infants) of vitamin A, in addition to standard treatment for pneumonia. They received further doses of the same regimen 4 and 8 months after hospital discharge. Sera from children were tested for HIV antibodies by enzyme-linked immunosorbent assay and Western blot tests. For positive children <15 months of age, HIV infection was confirmed by amplified heat-denatured HIV-p24 antigen assays with confirmatory neutralization assays. HIV status was ascertained for 648 of 687 enrolled children. The mean duration of follow-up was 24.4 months (SD = 12.1).
                Of 648 children 58 (9%) were HIV-infected. Compared with uninfected children, all-cause mortality was higher among HIV-infected children, as was mortality caused by pneumonia or diarrhea (P < 0.001 for each). Overall vitamin A supplements resulted in a 49% reduction in mortality [relative risk (RR), 0.51; 95% confidence interval (CI), 0.29 to 0.90, P = 0.02]. Vitamin A supplements reduced all-cause mortality by 63% among HIV-infected children (RR 0.37; CI 0.14 to 0.95, P = 0.04) and by 42% among uninfected children (RR 0.58, CI 0.28 to 1.19, P = 0.14). Vitamin A supplements were also associated with a 68% reduction in AIDS-related deaths (P = 0.05) and a 92% reduction in diarrhea-related deaths (P = 0.01).
                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.
Given the current evidence base, which is limited to fourteen relatively small trials all evaluating different macronutrient supplements in different populations at different stages of HIV infection and with varying treatment status, no firm conclusions can be drawn about the effects of macronutrient supplementation on morbidity and mortality in people living with HIV. It is, however, promising to see more studies being conducted in low-income countries, and particularly in children, where macronutrient supplementation both pre-antiretroviral treatment and in conjunction with antiretroviral treatment might prove to be beneficial.