Micronutrients delay immunological progression in treatment-naive patients

Effect of micronutrient supplementation on disease progression in asymptomatic, antiretroviral-naive, HIV-infected adults in Botswana: a randomized clinical trial.

Baum MK, Campa A, Lai S, Sales Martinez S, Tsalaile L, Burns P, Farahani M, Li Y, van Widenfelt E, Page JB, Bussmann H, Fawzi WW, Moyo S, Makhema J, Thior I,Essex M, Marlink R. JAMA. 2013 Nov 27;310(20):2154-63. doi: 10.1001/jama.2013.280923.

Importance: 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.

Design, setting, and participants: 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.

Interventions: Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo.

Main outcomes and measures: 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 (adjust ed 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 and relevance: 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.

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Editor’s notes: Micronutrient deficiencies are prevalent in people living with HIV and have been shown to be associated with disease progression. Previous studies have shown that micronutrient supplementation can improve the markers of disease progression in patients with advanced HIV; however this is the first study to explore this question in patients with early-stage disease. To be eligible for entry into this 24 month, double-blind, placebo-controlled trial patients had to have a CD4 count >350 cells/mm3 i.e., higher than the recommended threshold for initiation of antiretroviral therapy (ART) in Botswana. When compared to placebo, micronutrient supplementation with multivitamins (B, C, E) plus selenium was found to approximately half the risk of immunological decline. Likewise, the risk of disease progression (earliest of CD4 ≤250 cell/ mm3, AIDS-defining condition or death) was significantly reduced. This low cost intervention could act as an incentive to engage patients in pre-ART care, a particularly challenging time period in terms of retention in care.

Africa
Botswana
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