Micronutrient deficiencies less common in people taking antiretrovirals

A study team has found several vitamin and mineral deficiencies, noted as common before the widespread use of antiretrovirals, to be much less common in people on antiretroviral therapy. They also found these deficiencies to have relatively little effect on CD4 cell counts and HIV viral load.

For people with HIV, “which vitamins should I take?” is a simple question with a complicated answer. Most research to date has studied people who are not on antiretroviral treatment. Widespread micronutrient (vitamin and mineral) deficiencies (as measured by low blood serum levels) have been found in these people, and many of these have been associated with worse health outcomes.

Although supplement use is very common among HIV-positive people, studies have often been very inconsistent regarding their benefits, with some even showing worsened outcomes for certain supplements. Little research has been done on micronutrient levels and supplementation in HIV-positive people who are on therapy.

The Nutrition for Healthy Living study

Nutrition for Healthy Living (NFHL) is an ongoing cohort study of nutrition and HIV disease status in HIV-positive adults in Boston, Massachusetts and Providence, Rhode Island. In this component of the NFHL study (published in the December 1^st issue of the Journal of Acquired Immune Deficiency Syndromes), the researchers specifically looked at HIV-positive people on antiretroviral therapy. For each of four specific micronutrients – retinol (vitamin A), α-tocopherol (vitamin E), zinc, and selenium – they asked the following four questions:

• how many people on antiretrovirals are deficient in these micronutrients?
• how do these deficiencies affect viral load and CD4 levels?
• what are the effects of supplementation?
• how do these findings compare with other studies?

The study group was made up of 171 men and 117 women, seen between 2000 and 2003. All were on antiretroviral therapy, and the majority (62 – 69%) had undetectable viral loads. Most were in their mid-40s, and had been infected an average of ten years. The group was quite racially varied, and many were poor.

Specific results for Vitamin E

Serum levels of α-tocopherol (vitamin E) were found to be deficient (defined as less than 500 µg/dL) in 7% of the men and essentially none of the women. Consistent with previous studies, this deficiency did not correlate with any differences in CD4 count or viral load.

What were the results?

Except for zinc, deficiencies were much less common than those seen in people not on antiretrovirals. None of the micronutrient levels significantly affected CD4 counts. Viral loads tended to be slightly lower in people with higher zinc and selenium levels, although these were not statistically strong results. Results for retinol (vitamin A) were more complex, and are described in the ‘retinol’ section below. Supplement use did not have a significant effect on CD4 count or viral load for any of the micronutrients studied.

Selenium

Selenium deficiency was seen in 8% of the men and 3% of the women; much lower than some reported figures for people not on antiretrovirals. (A small study, mostly in injection drug users, reported 77% selenium deficiency rates in 1995.) The NFHL study defined selenium deficiency as serum levels less than 85 µg/L – levels which are definitely associated with increased mortality.

As with zinc, viral load levels varied slightly by selenium levels, and CD4s were not affected. Women with the lowest selenium levels tended to have the highest viral loads; there was no significant difference in men.

For zinc

Of the four nutrients studied, zinc was the only one found to be widely deficient: 40% of the men and 36% of the women had low zinc levels. (The NFHL defined ‘deficiency’ as serum zinc levels less than 670 µg/L: this is in the middle of the range of various levels used in other studies.)

The researchers did not find that zinc deficiency affected CD4 counts or had much effect on viral load. People with higher zinc levels tended to have lower viral loads, but this effect was slight and not statistically significant. While there was no evidence that zinc intake actually increased serum zinc levels, neither was there any indication that it was harmful.

The viral load findings, slight as they were, raise a question about cause and effect: could higher zinc cause better control of HIV viral load? This study cannot answer that question: it could be true, but so could the converse – that lower viral load causes increased zinc levels. (Since HIV itself uses zinc, lower levels of HIV – due to drug treatment – could free up zinc which would otherwise be used by the virus.)

Retinol (Vitamin A)

Serum retinol was deficient in 5% of the men and 14% of the women. (Deficiency was defined as less than 30 µg/dL.)

Effects of low retinol were the study’s oddest and most complex finding. In women, the lowest retinol levels were found in the women with the lowest viral loads; this was a statistically significant result. The same was true only for men with high CD4 counts (>350 cells/mm³). However, for men with lower CD4s (less than 350 cells/mm³), the opposite was true - higher retinol levels were found in those with lower viral loads. There was no explanation for these apparently contradictory findings, However, other studies have found that people with moderate levels of vitamin A intake are less likely to progress to AIDS than those with very low or very high intakes.

Limitations and Comments

The researchers concluded that “most of our participants had adequate serum levels of retinol, α-tocopherol, and selenium. Low serum zinc was common.” They also noted that “although micronutrient supplement use was relatively common, it was not significantly associated with improved HIV disease status.” However, ‘HIV disease status’ was only narrowly measured by CD4 counts and viral loads, and did not include any quality-of-life measures or clinical outcomes. Also, this study only looked at people on antiretroviral therapy, so it adds no knowledge about those who are not on these medications.