This clinical trial aims to evaluate if natural mixed carotenoids supplementation can improve the health and survival of acquired immunodeficiency syndrome (AIDS) patients.
A placebo-controlled, prospective, randomized, double-blind, multicenter clinical trial.
Community, tertiary care human immunodeficiency virus (HIV) clinics of the Canadian HIV Trials Network (CTN).
Three hundred and thirty-one adults with advanced AIDS on conventional management were recruited during routine clinic visits.
All participants, including 166 controls, received daily oral specially formulated multivitamins including vitamin A and trace elements; 165 treatment group participants received additional daily oral natural mixed carotenoids, equivalent to 120 000 IU (72 mg) of β-carotene daily. Follow-up was quarterly at routine clinic visits.
Mean (s.d.) follow-up was for 13 (6) months. Thirty-six participants died by 18 months. Serum carotene concentration <1.0 μmol/l was present in 16% participants at baseline. Despite variation in carotene content of the treatment medication, serum carotene concentrations increased significantly to twice the baseline levels to 18 months follow-up in participants who received carotenoids treatment compared with controls (P<0.0001). Although not statistically significant, mortality was increased in participants who did not receive carotenoids treatment compared with those who did (HR time to death 1.76, 95% CI 0.89, 3.47, P=0.11). In multivariate analysis, survival was significantly and independently improved in those with higher baseline serum carotene concentrations (P=0.04) or higher baseline CD4 T-lymphocyte counts (P=0.005). Adjusted mortality was also significantly and independently increased in those who did not receive carotenoids treatment compared with those who did (HR time to death 3.15, 95% CI 1.10, 8.98, P=0.03).
Low serum carotene concentration is common in AIDS patients and predicts death. Supplementation with micronutrients and natural mixed carotenoids may improve survival by correction of a micronutrient deficiency. Further studies are needed to corroborate findings and elucidate mechanism of action.
CTN and Community Research Initiative of Toronto (CRIT).
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We acknowledge the contribution of Lori Swick (deceased), The Ottawa Hospital, for assisting in development of the protocol, Dr John McDonald, USANA Health Sciences Inc., for development of the study medication, Dr Chester Myers (deceased) and Dr Ken Luby for designing the multivitamin and trace element preparation, Shideh Khorasheh and Susan Cleary for national coordination of the trial and Dr Dean Fergusson for a helpful review of the draft manuscript. We also wish to thank all study coordinators and participants.
This study was supported by the Canadian HIV Trials Network, Community Research Initiative of Toronto, USANA Health Sciences Inc. and AIDS Program Committee of the Ontario Ministry of Health. DWC received a Career Scientist Award of the Ontario Ministry of Health. The drugs used in this study were kindly provided by USANA Health Sciences Inc., Salt Lake City, Ut, USA.
None of the authors have any declared conflict of interest.
The findings of this study were presented in part at the 9th Canadian Association for HIV Research Conference, Montreal, Quebec, April 27–30, 2000, Abstract #214; and the XIII International AIDS Conference, Durban, South Africa, July 9–14, 2000, Abstract #MoPpB1017.
Guarantor: DW Cameron.
Contributors: DWC and JA are co-principal investigators; DWC is study chair and conceived the idea; NS, DWC and JA wrote the manuscript; DWC, JA, DZ, PMF and JS planned the study; DWC, RV, FS, MJG, SW, IS, JG, WFS, SC, AR, JC, ST, ET and PMF recruited and monitored study participants; JS managed data and methodology; JS and RW analyzed the data; NS and DWC compiled the statistical report and interpreted the results; DZ managed drug approval and study implementation; PP blindly adjudicated all AIDS-defining and adverse events. All authors contributed to the report.
CTN 091/CRIT Carotenoids Study Group
D William Cameron, The Ottawa Hospital, General Campus, Ottawa; David Burdge, Oak Tree Clinic, Vancouver; Shurjeel Choudhri, University of Manitoba; Jeff Cohen, Metropolitan Hospital, Windsor; Raymond Duperval, Sherbrooke Hospital, Sherbrooke; Julian Falutz, Montreal General Hospital, Montreal; Peter Ford, Queen's University, Kingston; John Gill, Foothills Hospital, Calgary; Janet Gilmour, St Joseph's Hospital, London; Patrice Junod, C du Quartier Latin, Montreal; Eric Lefebvre, Clinique L'Actuel, Montreal; Mark Miller, Jewish General Hospital, Montreal; Ann Phillips, St Michaels Hospital, Toronto; Kevin Gough, St Michael's Hospital, Toronto; Anita Rachlis, Sunnybrook Health Sciences Centre, Toronto; Sharon Walmsley and Irving Salit, The Toronto Hospital, Toronto; Roger Sandre, Haven Program, Sudbury; Walter Schlech III, Victoria General, Halifax; Fiona Smaill, McMaster University, Hamilton; Emil Toma, CHUM—Hotel Dieu, Montreal; Sylvie Trottier, Hopital Laval, Quebec City; Robert Voigt, Spectrum Health, Vancouver; Kurt Williams, Royal University Hospital, Saskatoon; James Austin, Community Research Initiative, Toronto; Peter Phillips, St Paul's Hospital, Vancouver. Appendix B Table
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Austin, J., Singhal, N., Voigt, R. et al. A community randomized controlled clinical trial of mixed carotenoids and micronutrient supplementation of patients with acquired immunodeficiency syndrome. Eur J Clin Nutr 60, 1266–1276 (2006). https://doi.org/10.1038/sj.ejcn.1602447
- carotenoids treatment
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