EAL

H/A: Micronutrient Supplementation (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The objective of this study was to determine the prevalence of low serum retinol, alpha tocopherol, zinc and selenium in HIV-infected subjects taking HAART and to assess the association of micronutrient levels with HIV disease status.

Inclusion Criteria:

HIV-infected adults 18 years of age or older
Taking part in the Nutrition for Healthy Living study in either Boston, Massachusetts or Providence, RI
Taking highly active antiretroviral therapy (HAART)
Seen in the clinic between September, 2000 and November, 2003
Frozen serum for micronutrient analysis
Men must have a C-reactive protein determination on the visit for the micronutrient analyses.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

Subjects were recruited through the Nutrition for Healthy Living study.

Design

Cross-sectional analysis of cohort data.

Statistical Analysis

Means and proportions for demographic, laboratory and other variables were calculated and compared between micronutrient quartiles using the Student T-test, Wilcoxon nonparametric test or Chi Square test
Association of micronutient quartiles with CD4 cell count, CD4 count less than 200 cells per mm³, HIV viral load (VL) and undetectable VL was assessed using adjusted multivariate regression
Statistical tests were two-sided; P-values were considered significant if less than 0.05.

Data Collection Summary:

Timing of Measurements

Blood was drawn at a NFHL study visit and serum was stored until analyses were completed. Analysis for the micronutrients retinol, alpha tocopherol, zinc and selenium were determined.

Dependent Variables

Serum retinol and alpha tocopherol levels
Serum zinc levels
Serum selenium levels
Dietary intake ascertained using a three-day food record or one-day or two-day dietary recall.

Independent Variables

HIV infection, CD4 count, log viral load.

Control Variables

Age
Gender
Race
Housing insecurity
Poverty levels.

Description of Actual Data Sample:

Initial N: 171 males, 117 females
Attrition (final N): As above
Age: Mean age for men, 44.9±7.5 years; women, 43.7±6.7 years.

Ethnicity

Men: 61% white, 26% African American, 8% Hispanic, 5% other
Women: 33% white, 48% African American , 13% Hispanic, 6% other.

Other Relevant Demographics

36% of men were below poverty index, 69 % of women were below poverty index.

Anthropometrics

Men: Mean CD4 count, 454±290 cells per mm³; mean log viral load, 2.82±0.93 copies per ml
Women: Mean CD4 count, 428±248 cells per mm³; mean log viral load, 2.92±0.94 copies per mL.

Location

Boston, MA and Providence, RI.

Summary of Results:

Micronutrient (Percentage of Low Serum Levels)	Men	Women
Retinol	5.3	13.7
Alpha tocopherol	7.1	0
Zinc	40	36
Selenium	7.7	3.4

Other Findings

No micronutrient was associated with CD4 cell-count-related disease status (total CD4 count or percentage with CD4 count less than 200 cells per mm³) in the multivariate models
Subjects in the upper quartiles of zinc had lower log viral load levels than those in the lowest quartile (significant for women)
In men, only zinc showed a trend for difference in disease status by quartiles
Log viral load was significantly lower among women in zinc quartile two (-0.60, P<0.01), quartile three (-0.77, P<0.01) and quartile four (-0.43, P<0.01)
Subjects in the upper quartiles of selenium also tended to have lower viral load levels compared with those in the lowest quartile
In women, viral load was higher among those in the upper three retinol quartiles compared with those in the lowest quartile (difference in mean log viral load was 0.81 in quartile two (P<0.01), 0.46 in quartile four (P<0.5)
The level of CD4 cell count influenced the association of retinol with log viral load in men, however
In men with CD4 counts higher than 350 cells per mm³, those with higher retinol had higher log viral loads compared with the lowest quartile, whereas in men with CD4 counts lower than 350, those with higher retinol levels had lower log viral loads compared with the lowest quartile.

Author Conclusion:

Low retinol, alpha tocopherol and selenium are uncommon in HIV-infected subjects on HAART. Most of our participants had adequate serum levels of retinol, alpha tocopherol and selenium. Zinc deficiency remains common, however. Decreased retinol levels in women and in men with CD4 counts higher than 350 cells per mm³ and increased zinc and selenium levels in both genders may be associated with improved virologic control. Although micronutrient supplement use was relatively common, it was not significantly associated with improved HIV disease status. There was no evidence that a higher dietary intake of zinc was harmful.

Funding Source:

Government:	National Institutes of Health, National Institute on Drug Abuse
University/Hospital:	Tufts University, Boston MA, Harvard University, Boston MA, Johns Hopkins University School of Medicine, Baltimore MD

Reviewer Comments:

Men and women had blood drawn and analyses completed at separate institutions and by different techniques.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	Yes
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	Yes
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	Yes
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	N/A
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes