Micronutrient supplements delay HIV disease progression for patients with higher CD4 cell counts

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Long-term micronutrient supplementation delays HIV disease progression in people with higher CD4 cell counts, results of a study published in the Journal of the American Medical Association shows. The research was conducted in Botswana and involved antiretroviral-naive people with CD4 cell counts above 350 cells/mm3. Supplementation with vitamins B, C and E plus selenium significantly slowed the rate of HIV disease progression.

“A single supplement providing the combination of multivitamins with B vitamins, vitamins C and E, and selenium, as compared with placebo, administered early in HIV disease, reduced the risk of reaching a CD4 cell count of 250 cell/mm3 or less in two years,” write the authors. “The benefit was also evident with an earlier end point of a CD4 cell count of 350 cells/mm3 or less, which is the current standard for starting ART [antiretroviral therapy] in Botswana.”

Vitamins B, C and E support immunity and selenium has been shown to reduce HIV replication in test tube studies.


disease progression

The worsening of a disease.


A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.


In HIV, an individual who is ‘treatment naive’ has never taken anti-HIV treatment before.

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.


A clinical trial where neither the researchers nor participants know which assigned treatment an individual participant in the trial is taking until after the end of the trial. This reduces the risk of biased results. 

Earlier research showed that micronutrient supplements slow the rate of HIV disease progression in people with advanced HIV disease. Supplementation with selenium alone has also shown benefits in a randomised trial. An international team of investigators wanted to see if supplementation was also beneficial for people with higher CD4 cell counts, and in particular, whether it might delay the need for antiretroviral treatment in this group of people with HIV.

They designed a double-blind, placebo-controlled study involving 878 antiretroviral-naive people (people who had not previously taken HIV treatment) in Botswana. All had HIV-1 subtype C, had a CD4 cell count above 350 cells/mm3, were of normal body weight and were asymptomatic.

The participants were randomised into four study arms:

  • Placebo.
  • Multivitamins (B, D and E) alone (thiamin 20mg; riboflavin 20mg; niacin 100mg; vitamin B6 25mg; vitamin B12 50μg; folic acid 800μg; vitamin C 500mg; and vitamin E 30mg).
  • Selenium alone (200μg per day)
  • Multivitamins plus selenium.

Micronutrients were taken daily.

The study was conducted between 2004 and 2009 and follow-up lasted 24 months. The main outcome was progression to a CD4 cell count below 250 cells/mm3. Secondary outcomes were progression to a combined outcome of a CD4 cell count below 250 cells/mm3, an AIDS-events or AIDS-related death, or a CD4 cell count below 350 cells/mm3.

Participants in the study had a median CD4 cell count of 420 cells/mm3 at baseline and a third had a count above 500 cells/mm3. Median baseline viral load was approximately 15,000 copies/ml.

Outcomes clearly showed the benefits of supplementation.

Compared to people in the placebo arm, individuals who received multivitamins alone or multivitamins plus selenium were significantly less likely to experience a fall in their CD4 cell count to below 250 cells/mm3 (p = 0.04 and p = 0.02, respectively). Selenium supplementation alone did not reduce the risk of the CD4 cell count falling below this threshold.

For secondary outcomes, only supplementation with multivitamins and selenium reduced the risk of progressing to the composite outcome of CD4 cell count below 250 cells/mm3, AIDS-events or AIDS-related death (p = 0.04). Similarly, only combined therapy with the multivitamins and selenium were shown to reduce the risk of progression to a CD4 cell count below 350 cells/mm3 (p = 0.04).

Multivariate analysis controlling for age, sex, and baseline characteristics including CD4 cell count and viral load confirmed that supplementation with multivitamins plus selenium reduced the risk of CD4 cell count falling to below 250 cells/mm3 (p = 0.01) and also the risk of progressing to secondary outcomes (p = 0.03). Neither multivitamins alone nor selenium alone reduced the risk of disease progression.

Supplementation had no effect on viral load.

No adverse events were related to any of the study medication, and 90% of participants had high levels of medication adherence (at least 96% of doses taken).

“These results…demonstrate the effectiveness and safety of multivitamins and selenium when administered together in a single supplement in slowing HIV disease progression in the early stage of disease prior to ART,” comment the investigators. “The evidence from our study presented herein supports the provision of low-cost supplementation with multivitamins combined with selenium for HIV-infected individuals in early stages of the disease who are ART-naïve to prolong adequate immune response and prevent AIDS-defining conditions.”


Baum MK et al. Effect of micronutrient supplementation on disease progression in asymptomatic, antiretroviral-naïve, HIV-infected adults in Botswana: a randomized clinical trial. JAMA 310: 2154-63, 2013. (Full text article freely available).