title: Effect of micronutrient supplementation on disease progression in asymptomatic, antiretroviral-naive, HIV-infected adults in Botswana: a randomized clinical trial.
abstract: OBJECTIVE
  Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive.
  
  
  OBJECTIVE
  To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive.
  
  
  METHODS
  Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), selenium alone, or multivitamins with selenium vs placebo in a factorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009.
  
  
  METHODS
  Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo.
  
  
  METHODS
  Reaching a CD4 cell count less than 200/μL until May 2008; after this date, reaching a CD4 cell count of 250/μL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study.
  
  
  RESULTS
  There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/μL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of combined outcomes for disease progression (CD4 cell count ≤250/μL, AIDS-defining conditions, or AIDS-related death, whichever occurred earlier [adjusted HR, 0.56; 95% CI, 0.33-0.95; P = .03; AER, 6.48/100 person-years; censoring rate, 0.90; 23 events]). There was no effect of supplementation on HIV viral load. Multivitamins alone and selenium supplementation alone were not statistically different from placebo for any end point. Reported adverse events were adjudicated as unlikely to be related to the intervention, and there were no notable differences in incidence of HIV-related and health-related events among study groups.
  
  
  CONCLUSIONS
  In ART-naive HIV-infected adults, 24-month supplementation with a single supplement containing multivitamins and selenium was safe and significantly reduced the risk of immune decline and morbidity. Micronutrient supplementation may be effective when started in the early stages of HIV disease.
authors.affiliation: Florida International University, R. Stempel College of Public Health and Social Work, Miami.
authors.forename: Marianna K
authors.initials: MK
authors.lastname: Baum
authors.forename: Adriana
authors.initials: A
authors.lastname: Campa
authors.forename: Shenghan
authors.initials: S
authors.lastname: Lai
authors.forename: Sabrina
authors.initials: S
authors.lastname: Sales Martinez
authors.forename: Lesedi
authors.initials: L
authors.lastname: Tsalaile
authors.forename: Patricia
authors.initials: P
authors.lastname: Burns
authors.forename: Mansour
authors.initials: M
authors.lastname: Farahani
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
authors.forename: Erik
authors.initials: E
authors.lastname: van Widenfelt
authors.forename: John Bryan
authors.initials: JB
authors.lastname: Page
authors.forename: Hermann
authors.initials: H
authors.lastname: Bussmann
authors.forename: Wafaie W
authors.initials: WW
authors.lastname: Fawzi
authors.forename: Sikhulele
authors.initials: S
authors.lastname: Moyo
authors.forename: Joseph
authors.initials: J
authors.lastname: Makhema
authors.forename: Ibou
authors.initials: I
authors.lastname: Thior
authors.forename: Myron
authors.initials: M
authors.lastname: Essex
authors.forename: Richard
authors.initials: R
authors.lastname: Marlink
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D001902:Botswana; D018791:CD4 Lymphocyte Count; D003677:Deficiency Diseases / Q000150:complications / Q000188:drug therapy*; D019587:Dietary Supplements; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D012643:Selenium / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load; D014815:Vitamins / Q000008:administration & dosage*
chemical_list: D044966:Anti-Retroviral Agents; D014815:Vitamins; D012643:Selenium