Micronutrient deficiency and treatment adherence in a randomized controlled trial of micronutrient supplementation in ART-naïve persons with HIV.
BACKGROUND
The MAINTAIN study is an on-going RCT comparing high-dose micronutrient and anti-oxidant supplementation versus recommended daily allowance (RDA) vitamins in slowing HIV immune deficiency progression in ART-naïve people with HIV infection.


OBJECTIVE
We planned analysis of the first 127 participants to determine the baseline prevalence of serum micronutrient deficiencies and correlates, as well as tolerance and adherence to study interventions.


METHODS
Participants receive eight capsules twice daily of 1) high-dose or 2) RDA supplements for two years and are followed-up quarterly for measures of immune deficiency progression, safety and tolerability. Regression analysis was used to identify correlates of micronutrient levels at baseline. Adherence was measured by residual pill count, self-report using the General Treatment Scale (GTS) and short-term recall HIV Adherence Treatment Scale (HATS).


RESULTS
Prior micronutrient supplementation (within 30 days) was 27% at screening and 10% of study population, and was not correlated with baseline micronutrient levels. Low levels were frequent for carotene (24%<1 nmol/L), vitamin D (24%<40 nmol/L) and serum folate (20%<15 nmol/L). The proportion with B12 deficiency (<133 pmol/L) was 2.4%. Lower baseline levels of B12 correlated lower baseline CD4 count (r = 0.21, p = 0.02) with a 21 pmol/L reduction in B12 per 100 cells/µL CD4. Vitamin D levels were higher in men (p<0.001). After a median follow-up of 1.63 years, there were 19 (15%) early withdrawals from the study treatment. Mean treatment adherence using pill count was 88%. Subjective adherence by the GTS was 81% and was moderately but significantly correlated with pill count (r = 0.29, p<0.001). Adherence based on short-term recall (HATS) was >80% in 75% of participants.


CONCLUSIONS
Micronutrient levels in asymptomatic HIV+ persons are in keeping with population norms, but micronutrient deficiencies are frequent. Adherence levels are high, and will permit a valid evaluation of treatment effects.


BACKGROUND
ClinicalTrials.gov NCT00798772.
CIHR Canadian HIV Trials Network (CTN), Vancouver, British Columbia, Canada ; Division of Infectious Diseases, Department of Medicine, University of Ottawa at the Ottawa Hospital, Ottawa, Ontario, Canada.
Louise
L
Balfour
CIHR Canadian HIV Trials Network (CTN), Vancouver, British Columbia, Canada ; Clinical Epidemiology Program, University of Ottawa at The Ottawa Hospital Research Institute (OHRI), Ottawa, Ontario, Canada.
Johanna N
JN
Spaans
Clinical Epidemiology Program, University of Ottawa at The Ottawa Hospital Research Institute (OHRI), Ottawa, Ontario, Canada.
Dean
D
Fergusson
Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada.
Harold
H
Huff
Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada.
Edward J
EJ
Mills
Division of Infectious Diseases, Department of Medicine, University of Ottawa at the Ottawa Hospital, Ottawa, Ontario, Canada ; Clinical Epidemiology Program, University of Ottawa at The Ottawa Hospital Research Institute (OHRI), Ottawa, Ontario, Canada.
Charles J
CJ
la Porte
CIHR Canadian HIV Trials Network (CTN), Vancouver, British Columbia, Canada ; Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Sharon
S
Walmsley
CIHR Canadian HIV Trials Network (CTN), Vancouver, British Columbia, Canada ; Clinical Epidemiology Program, University of Ottawa at The Ottawa Hospital Research Institute (OHRI), Ottawa, Ontario, Canada.
Neera
N
Singhal
CIHR Canadian HIV Trials Network (CTN), Vancouver, British Columbia, Canada.
Ron
R
Rosenes
CIHR Canadian HIV Trials Network (CTN), Vancouver, British Columbia, Canada ; Division of Infectious Diseases, Department of Medicine, University of Ottawa at the Ottawa Hospital, Ottawa, Ontario, Canada.
Nancy
N
Tremblay
CIHR Canadian HIV Trials Network (CTN), Vancouver, British Columbia, Canada ; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
M John
MJ
Gill
CIHR Canadian HIV Trials Network (CTN), Vancouver, British Columbia, Canada ; Department of Medicine, The University of Ottawa, Ottawa, Ontario, Canada.
Hugues
H
Loemba
CIHR Canadian HIV Trials Network (CTN), Vancouver, British Columbia, Canada ; Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
Brian
B
Conway
CIHR Canadian HIV Trials Network (CTN), Vancouver, British Columbia, Canada ; Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Anita
A
Rachlis
CIHR Canadian HIV Trials Network (CTN), Vancouver, British Columbia, Canada ; Division of Infectious Diseases, Department of Medicine, University of Western Ontario, London, Ontario, Canada.
Edward
E
Ralph
CIHR Canadian HIV Trials Network (CTN), Vancouver, British Columbia, Canada ; Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Mona
M
Loutfy
Ottawa Methods Centre, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Ranjeeta
R
Mallick
Clinical Epidemiology Program, University of Ottawa at The Ottawa Hospital Research Institute (OHRI), Ottawa, Ontario, Canada.
Rika
R
Moorhouse
CIHR Canadian HIV Trials Network (CTN), Vancouver, British Columbia, Canada ; Division of Infectious Diseases, Department of Medicine, University of Ottawa at the Ottawa Hospital, Ottawa, Ontario, Canada ; Clinical Epidemiology Program, University of Ottawa at The Ottawa Hospital Research Institute (OHRI), Ottawa, Ontario, Canada.
D
D
William Cameron
D000328:Adult; D019380:Anti-HIV Agents; D018791:CD4 Lymphocyte Count; D002338:Carotenoids / Q000008:administration & dosage / Q000097:blood; D004032:Diet; D019587:Dietary Supplements; D018450:Disease Progression; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood; D015658:HIV Infections / Q000150:complications / Q000178:diet therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D008297:Male; D018977:Micronutrients / Q000008:administration & dosage*; D008875:Middle Aged; D010349:Patient Compliance; D064167:Recommended Dietary Allowances; D057566:Self Report; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000097:blood; D014806:Vitamin B 12 Deficiency / Q000150:complications / Q000178:diet therapy* / Q000276:immunology / Q000821:virology; D014807:Vitamin D / Q000008:administration & dosage / Q000097:blood; D014808:Vitamin D Deficiency / Q000150:complications / Q000178:diet therapy* / Q000276:immunology / Q000821:virology
D019380:Anti-HIV Agents; D018977:Micronutrients; D014807:Vitamin D; D002338:Carotenoids; D005492:Folic Acid; D014805:Vitamin B 12