Efficacy of vitamin D3supplementation in reducing incidence of pulmonary tuberculosis and mortality among HIV-infected Tanzanian adults initiating antiretroviral therapy: study protocol for a randomized controlled trial.
HIV-infected adults initiating antiretroviral therapy (ART) in sub-Saharan Africa continue to experience high rates of morbidity and mortality during the initial months of treatment. Observational studies in high-income and resource-limited settings indicate that HIV-infected adults with low vitamin D levels may be at increased risk of mortality, HIV disease progression, and incidence of pulmonary tuberculosis (TB). As a result, vitamin D3supplementation may improve survival and treatment outcomes for HIV-infected adults initiating ART.



The Trial of Vitamins-4 (ToV4) is an individually randomized, double-blind, placebo-controlled trial of vitamin D3(cholecalciferol) supplementation conducted among 4000 HIV-infected adults with low vitamin D levels [25-hydroxyvitamin D (25(OH)D) <30 ng/mL] initiating ART in Dar es Salaam, Tanzania. The two primary aims of the trial are to determine the effect of a vitamin D3supplementation regimen on incidence of (1) mortality and (2) pulmonary TB as compared to a matching placebo regimen. The primary safety outcome of the study is incident hypercalcemia. The investigational vitamin D3regimen consists of oral supplements containing 50,000 IU vitamin D3taken under direct observation at randomization and once a week for 3 weeks (four doses) followed by daily oral supplements containing 2000 IU vitamin D3taken at home from the fourth week until trial discharge at 1 year post ART initiation. Trial participants are followed up at weekly clinic visits during the first month of ART and at monthly clinic visits thereafter until trial discharge at 1 year post ART initiation. Secondary aims of the trial are to examine the effect of the vitamin D3regimen on CD4 T cell reconstitution, incidence of non-TB comorbidities, body mass index (BMI), depression and anxiety, physical activity, bone health, and immunologic biomarkers.



The ToV4 will provide causal evidence on the effect of vitamin D3supplementation on incidence of pulmonary TB and mortality among HIV-infected Tanzanian adults initiating ART. The trial will also give insight to whether vitamin D3supplementation trials for the prevention of pulmonary TB should be pursued in HIV-uninfected populations.



ClinicalTrials.gov, NCT01798680 . Registered on 21 February 2013.
Department of Global Health and Population, Harvard T.H. Chan School of Public Health, 665 Huntington Ave, Building I Room 1104C, Boston, MA, 02115, USA. csudfeld@hsph.harvard.edu.
Christopher R
CR
Sudfeld
Management and Development for Health, Dar es Salaam, Tanzania.|Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Ferdinand
F
Mugusi
Management and Development for Health, Dar es Salaam, Tanzania.|Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Said
S
Aboud
Management and Development for Health, Dar es Salaam, Tanzania.|Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Tumaini J
TJ
Nagu
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Molin
M
Wang
Department of Global Health and Population, Harvard T.H. Chan School of Public Health, 665 Huntington Ave, Building I Room 1104C, Boston, MA, 02115, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.|Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Wafaie W
WW
Fawzi
D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D000284:Administration, Oral; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000009:adverse effects; D002985:Clinical Protocols; D060085:Coinfection; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D016867:Immunocompromised Host; D015994:Incidence; D009752:Nutritional Status; D065840:Protective Factors; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D013636:Tanzania / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D014808:Vitamin D Deficiency / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality
D044966:Anti-Retroviral Agents; D002762:Cholecalciferol
Cholecalciferol; HIV; Micronutrient; Nutrition; Tanzania; Tuberculosis; Vitamin D