Effect of high-dose vs standard-dose multivitamin supplementation at the initiation of HAART on HIV disease progression and mortality in Tanzania: a randomized controlled trial.
BACKGROUND
Large randomized trials have previously shown that high-dose micronutrient supplementation can increase CD4 counts and reduce human immunodeficiency virus (HIV) disease progression and mortality among individuals not receiving highly active antiretroviral therapy (HAART); however, the safety and efficacy of such supplementation has not been established in the context of HAART.


OBJECTIVE
To test the hypothesis that high-dose multivitamin supplementation vs standard-dose multivitamin supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients with HIV initiating HAART.


METHODS
A randomized, double-blind, controlled trial of high-dose vs standard-dose multivitamin supplementation for 24 months in 3418 patients with HIV initiating HAART between November 2006 and November 2008 in 7 clinics in Dar es Salaam, Tanzania. INTERVENTION The provision of daily oral supplements of vitamin B complex, vitamin C, and vitamin E at high levels or standard levels of the recommended dietary allowance.


METHODS
The composite of HIV disease progression or death from any cause.


RESULTS
The study was stopped early in March 2009 because of evidence of increased levels of alanine transaminase (ALT) in patients receiving the high-dose multivitamin supplement. At the time of stopping, 3418 patients were enrolled (median follow-up, 15 months), and there were 2374 HIV disease progression events and 453 observed deaths (2460 total combined events). Compared with standard-dose multivitamin supplementation, high-dose supplementation did not reduce the risk of HIV disease progression or death. The absolute risk of HIV progression or death was 72% in the high-dose group vs 72% in the standard-dose group (risk ratio [RR], 1.00; 95% CI, 0.96-1.04). High-dose supplementation had no effect on CD4 count, plasma viral load, body mass index, or hemoglobin level concentration, but increased the risk of ALT elevations (1239 events per 1215 person-years vs 879 events per 1236 person-years; RR, 1.44; 95% CI, 1.11-1.87) vs standard-dose supplementation. CONCLUSION In adults receiving HAART, use of high-dose multivitamin supplements compared with standard-dose multivitamin supplements did not result in a decrease in HIV disease progression or death but may have resulted in an increase in ALT levels.


BACKGROUND
Clinicaltrials.gov Identifier: NCT00383669.
Departments of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. sisanaka@hsph.harvard.edu
Sheila
S
Isanaka
Ferdinand
F
Mugusi
Claudia
C
Hawkins
Donna
D
Spiegelman
James
J
Okuma
Said
S
Aboud
Chalamilla
C
Guerino
Wafaie W
WW
Fawzi
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001205:Ascorbic Acid / Q000008:administration & dosage*; D015992:Body Mass Index; D018791:CD4 Lymphocyte Count; D019587:Dietary Supplements; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D009752:Nutritional Status; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load; D014803:Vitamin B Complex / Q000008:administration & dosage*; D014810:Vitamin E / Q000008:administration & dosage*; D014815:Vitamins / Q000008:administration & dosage*
D014815:Vitamins; D014803:Vitamin B Complex; D014810:Vitamin E; D001205:Ascorbic Acid