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