Antiretroviral therapy, gradually becoming the standard of care in developing countries, confers enormous benefits and yet substantial morbidity remains in HIV-positive populations. Multivitamin supplements have immune-enhancing effects, and high-dose supplements were found to improve immunologic status and reduce morbidity and mortality among HIV-positive Tanzanian women in pre-HAART stages of disease. High doses of these supplements are thought to be required to restore adequate nutrient levels in the context of HIV infection. Therefore, we propose a double-blind, placebo- controlled, randomized trial of the same high-dose multivitamin supplements (containing B-vitamins, C, and E) to determine their efficacy in slowing disease progression, indicated by increased CD4 count, weight gain, and improved quality of life, and decreased morbidity, mortality, and drug-related adverse events (i.e. peripheral neuropathy, anemia, and diarrhea). We will enroll 400 men and women in the rural Kayunga district of Uganda, who are receiving or have recently initiated HAART. At baseline and monthly thereafter, research physicians and nurses at two study clinics will assess each participant's clinical status and undertake study procedures. Each participant will be followed for 18 months or until his /her death or loss to follow-up. Home visits will be conducted if participants miss their scheduled clinic appointments. We will perform nutritional assessments (anthropometry and dietary intake) at enrollment and several follow-up points, and laboratory measurements (CD4 cell counts and complete blood counts) every six months. Importantly, all study participants will continue receiving the standard of care according to national guidelines for the entire study period. Multivitamins could be a low-cost, adjunct therapy for helping to alleviate disease burden and elevate quality of life in HIV-infected individuals on HAART. At the same time, their efficacy could help preserve limited drug regimens in developing settings by postponing the need for switches to second line regimens of HAART. Our application represents collaboration between the Harvard School of Public Health, Walter Reed Program and Makerere University in Kampala, Uganda. The widespread use of antiretroviral drugs in developing settings is becoming a reality, yet these potent, life-saving drugs have recognized limitations. Multivitamin supplements represent a possible low-cost, adjunct therapy with immune-enhancing properties that could slow disease progression among HIV-infected individuals on HAART. In particular, multivitamins might confer important clinical benefits that would help preserve limited drug regimens in developing countries amidst increasing viral resistant HIV strains.

Public Health Relevance

The widespread use of antiretroviral drugs in developing settings is becoming a reality, yet these potent, life-saving drugs have recognized limitations. Multivitamin supplements represent a possible low-cost, adjunct therapy with immune-enhancing properties that could slow disease progression among HIV-infected individuals on HAART. In particular, multivitamins might confer important clinical benefits that would help preserve limited drug regimens in developing countries amidst increasing viral resistant HIV strains.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD060333-05
Application #
8307372
Study Section
Special Emphasis Panel (ZHD1-DSR-A (22))
Program Officer
Raiten, Daniel J
Project Start
2008-09-30
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$303,999
Indirect Cost
$54,222
Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Kyeyune, Rachel; Saathoff, Elmar; Ezeamama, Amara E et al. (2014) Prevalence and correlates of cytopenias in HIV-infected adults initiating highly active antiretroviral therapy in Uganda. BMC Infect Dis 14:496