A big boost of vitamins won’t help outcomes in HIV for individuals starting treatment, a trial showed.
High-dose daily multivitamins started at the initiation of highly-active antiretroviral treatment (HAART) had no impact on AIDS-related mortality (4% versus 4%, RR 1.14, 95% CI 0.82 to 1.58) or on disease progression compared with a standard multivitamin providing only the daily recommended amounts, Sheila Isanaka, ScD, of Harvard School of Public Health, and colleagues found.
Other markers like CD4 count and plasma viral load also showed no advantage for the higher vitamin dose, while there was a signal for concern with elevated liver enzymes, they reported in the Oct. 17 issue of the Journal of the American Medical Association.
Multivitamins do play a crucial role in supporting the immune system, but more may not be better, the researchers concluded.
“In the absence of clear evidence of the benefit of high-dose micronutrient supplementation on morbidity and mortality in adults receiving HAART, it is prudent to follow current recommendations to promote and support adequate dietary intake of micronutrients at recommended daily allowance levels,” they wrote.
Prior trials had shown high-dose supplements to improve outcomes among infected individuals not yet on HAART, but results have been mixed in the small randomized studies that had been done in the context of HAART.
For an adequately powered look at safety and efficacy, Isanaka’s group randomized 3,418 patients to double-blind multivitamin supplementation starting at the time of HAART initiation at one of seven clinics in Dar es Salaam, Tanzania.
Based on some observational evidence that HIV patients needed higher intakes to achieve normal serum concentrations, the high-dose multivitamin contained two to 21 times the recommended daily allowance (RDA) for the B vitamins, double the daily recommended level of vitamin E, and 6 times the daily requirement of vitamin C.
The control group got a daily supplement containing just the recommended daily allowance of these vitamins “rather than placebo, to increase the generalizability of our findings to patients in developed and developing countries where a standard RDA multivitamin supplement may be consumed.”
The study had to be stopped early after 15 months due to elevated alanine transaminase levels in the high-dose group. Overall, 38% of the patients had levels above normal, which was 44% more likely with the high-dose multivitamin (P=0.006).
The researchers called this a concern but noted that there’s no plausible mechanism, since prior studies have not shown such an effect in any setting with high-dose multivitamins.
The only other difference in adverse events between the groups was neuropathy, which was actually less common in the high-dose supplement group (incidence rate ratio 0.81, P=0.004), possibly because vitamin E deficiency has been linked to peripheral neuropathy.
The primary endpoint of HIV progression or death from any cause occurred in an identical 72% of patients in both groups.
Other endpoints came out similar for the high-dose versus standard-dose groups as well:
All-cause mortality (14% versus 13%, risk ratio 1.06, 95% CI 0.89 to 1.26)
CD4 count (mean difference −6/μL, 95% CI −16 to 4/μL)
Plasma viral load (mean difference −0.1 log copies/mL, 95% CI −0.4 to 0.3 log copies/mL)
However, one subanalysis suggested a 36% higher risk of death, albeit nonsignificant, among severely malnourished HIV patients taking high-dose multivitamins compared with the standard dose (38% versus 28% died, P=0.11).
HIV-associated wasting may disturb the body’s ability to cope with the extra vitamins akin to “re-feeding syndrome,” so holding multivitamins until after a period of stabilization on antiretrovirals might need to be considered, the investigators suggested.
The lack of benefit in this study of extra vitamins compared with prior studies may reflect the choice of comparator regimens, since placebo rather than the standard RDA had been used in the prior trials, Isanaka’s group pointed out.
“As different doses may have different effects, dose-finding trials with a placebo control are warranted to confirm the potential benefits of multivitamin supplementation on clinical outcomes, and to identify the lowest safe and effective dose in the context of HAART,” they wrote.
The study was supported by a grant from the National Institute of Child Health and Human Development.
The researchers reported having no conflicts of interest to disclose.
Primary source: Journal of the American Medical Association
Isanaka S, et al “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” JAMA 2012; 308 (15): 1535-1544.