Abstract

Tuberculosis is one of the leading causes of mortality worldwide, accounting for an estimated three million deaths annually. Micronutrient deficiencies are common during HIV infection and during pulmonary tuberculosis, and micronutrient deficiencies are associated with impaired immunity and increased morbidity and mortality. Despite adequate chemotherapy for tuberculosis, the morbidity and mortality of HIV-infected adults with pulmonary tuberculosis remains extremely high. The goal of this ongoing Phase III randomized, double-blind, controlled clinical trial is to determine whether a daily multivitamin (vitamins and minerals) supplement can reduce morbidity and mortality of HIV-infected adults with pulmonary tuberculosis in Malawi. All participants receive standard tuberculosis chemotherapy for eight months as per the Malawi National Tuberculosis Control Programme, and the total duration of follow-up in the trial is twenty-four months. The trial has a Community Advisory Board which consists of local community members and participants. The original sample size of the trial was reduced to 500 HIV-infected adults in order to complete enrollment within the study period and deal with a budget reduction. Interim analyses conducted for the NIAID HIV Therapeutic Clinical Trials Data and Safety Monitoring Board (DSMB) at NIH show that the trial has been conducted with steady enrollment, good adherence to supplementation, and high follow-up. The DSMB has recommended that the sample size of this trial be increased to have at least 80% power to detect a 20% reduction in mortality. To meet this recommendation, we propose to increase the sample size to 840 HIV-infected adults with pulmonary tuberculosis. The trial also includes 300 HIV-negative adults with pulmonary tuberculosis in order to reduce stigmatization. If this study demonstrates that a multivitamin supplement can reduce morbidity and mortality of HIV-infected adults with pulmonary tuberculosis, this appropriate, low cost intervention could be integrated with tuberculosis treatment to improve health and survival of HIV-infected individuals in developing countries.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI041956-07
Application #
6776988
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Laughon, Barbara E
Project Start
1998-09-15
Project End
2006-02-28
Budget Start
2004-03-01
Budget End
2005-02-28
Support Year
7
Fiscal Year
2004
Total Cost
$618,234
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Dayhoff-Brannigan, Margaret; Ferrucci, Luigi; Sun, Kai et al. (2008) Oxidative protein damage is associated with elevated serum interleukin-6 levels among older moderately to severely disabled women living in the community. J Gerontol A Biol Sci Med Sci 63:179-83
Beck, Justine; Ferrucci, Luigi; Sun, Kai et al. (2008) Circulating oxidized low-density lipoproteins are associated with overweight, obesity, and low serum carotenoids in older community-dwelling women. Nutrition 24:964-8
Semba, Richard D; Varadhan, Ravi; Bartali, Benedetta et al. (2007) Low serum carotenoids and development of severe walking disability among older women living in the community: the women's health and aging study I. Age Ageing 36:62-7
Semba, Richard D; Ricks, Michelle O; Ferrucci, Luigi et al. (2007) Types of anemia and mortality among older disabled women living in the community: the Women's Health and Aging Study I. Aging Clin Exp Res 19:259-64
Semba, R D; Kumwenda, J; Zijlstra, E et al. (2007) Micronutrient supplements and mortality of HIV-infected adults with pulmonary TB: a controlled clinical trial. Int J Tuberc Lung Dis 11:854-9
Bartali, Benedetta; Semba, Richard D; Frongillo, Edward A et al. (2006) Low micronutrient levels as a predictor of incident disability in older women. Arch Intern Med 166:2335-40
Semba, Richard D; Bartali, Benedetta; Zhou, Jing et al. (2006) Low serum micronutrient concentrations predict frailty among older women living in the community. J Gerontol A Biol Sci Med Sci 61:594-9
Ray, Amanda L; Semba, Richard D; Walston, Jeremy et al. (2006) Low serum selenium and total carotenoids predict mortality among older women living in the community: the women's health and aging studies. J Nutr 136:172-6
Michelon, Elisabete; Blaum, Caroline; Semba, Richard D et al. (2006) Vitamin and carotenoid status in older women: associations with the frailty syndrome. J Gerontol A Biol Sci Med Sci 61:600-7
Semba, R D; Blaum, C S; Bartali, B et al. (2006) Denture use, malnutrition, frailty, and mortality among older women living in the community. J Nutr Health Aging 10:161-7

Showing the most recent 10 out of 39 publications