EAL

H/A: Caloric Needs (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The aims of this study were to examine the accuracy of prediction equations based on height, weight and age and those based on fat-free mass for assessing REE and to determine their utility in men with HIV/AIDS in the era of highly active antiretroviral therapy
A secondary aim of this study was to determine if REE calculated to account for body composition is significantly different in those reporting lipodystrophy
The authors also wanted to determine if REE was affected by weight loss in this patient group and they wanted to examine any correlations between REE and the markers of disease progression.

Inclusion Criteria:

Participation in HIV-related nutrition studies at the centers.

Exclusion Criteria:

None given.

Description of Study Protocol:

Recruitment

HIV-positive men were recruited from the Royal Prince Alfred Hospital HIV/AIDS service and the Albion Street Centre, an ambulatory care facility for people with HIV/AIDS
Subjects were participating in HIV-related nutrition studies at these centers
A convenience sample of healthy male control subjects with similar age and weight to the initial HIV subjects was recruited from the staff at the centers.

Design

Cross-sectional.

Blinding Used

Implied for measurements.

Intervention

None.

Statistical Analysis

Variables between groups were compared using independent sample T-tests
Analysis of variance was used when there were more than two groups for comparison with post-hoc analysis using Tukey's test
Multiple linear regression was used to determine the relationship between variables and to develop the prediction equations. Variables of interest were included in the model as well as potential confounding variables (age, intake, smoking, activity levels, viral load, CD4 T-cell count and WHR).
Forward stepwise regression analysis was used to determine the best model for the prediction equation. A bootstrap resampling procedure was used to calculate the true prediction error of the best model.
Bias was determined and paired T-tests were used to ascertain if the differences between measured REE and the predicted value were significant for the REE prediction equations
Analysis of covariance was used to determine if dietary intake was significantly different between the three HIV-positive groups when age, weight, height and activity level were added as covariates
To compare HIV-positive and control groups, the general linear model procedure was used to estimate adjusted means in a univariate analysis of covariance. Interaction terms were initially included in the analysis to evaluate the homogeneity of slopes assumption.
Fat mass was also adjusted for by using analysis of covariance.
Post-hoc analysis of main effects was conducted with a Bonferroni adjustment for multiple comparisons.

Data Collection Summary:

Timing of Measurements

Baseline measures
All measures except dietary intake and activity level were conducted on the same day after a 12-hour overnight fast.

Dependent Variables

Weight and height
Fat-free mass estimated using bioelectrical impedance analysis
Fat mass calculated by arithmetic deduction from body weight and expressed as a percentage thereof
Dietary intake was assessed using a three-day estimated food record:

Subjects recorded weight and described the contents of all items consumed (food and fluid)
Portion sizes were estimated when weight was unavailable.

Activity levels were assessed using a three-day exercise diary where subjects documented periods of physical activity: Activity levels were then estimated on a scale of one to five, to match the descriptions provided with the Harris & Benedict equation
REE measured by indirect calorimetry, using a DeltaTrac II Metabolic Monitor.

Independent Variables

HIV-positive subjects were divided into three groups a priori:

Clinically documented unintentional ongoing weight loss of 5% or more of usual body weight within the last six months, without evidence of lipodystrophy
Those with lipodystrophy who were weight-stable (±5% usual weight)
Those without lipodystrophy who were weight stable (±5% usual weight).

Comparison groups

HIV-positive (total)
Weight-stable: ±5% of usual weight
Lipodystrophy (LD): Defined as peripheral subcutaneous fat wasting or visceral adiposity and confirmed by clinical examination
Weight loss: At least 5% of usual weight within six months
Control.

Control Variables

Age
Intake
Smoking
Activity levels
Viral load
CD4 T-cell count
WHR.

Description of Actual Data Sample:

Initial N: 70 HIV-positive males and 16 healthy male controls
Attrition (final N): 70 and 16
Age: 37 to 44 years
Ethnicity: Not given
Other relevant demographics: Not given.

Anthropometrics

See Table Two in Summary of Results for anthropometric information
Disease information: 62 of the HIV-positive subjects were taking antiretroviral therapy; seven were antiretroviral naive; one was having a planned treatment interruption and currently not using HAART.

Location

Royal Prince Alfred Hospital HIV/AIDS service and the Albion Street Centre, an ambulatory care facility for people with HIV/AIDS.

Summary of Results:

Table Two: Subject Characteristics

Variables	HIV-Positive (N=70)	Weight Stable (N=23)	LD (N=30)	Weight Loss (N=17)	Control (N=16)
Age (Years)	42.67±11.17	41.00±11.18	44.10±12.11	42.41±9.62	37.25±5.84
Weight (kg)	68.44±11.12	70.42±10.14	70.33±10.14	62.42±10.72^a	74.14±7.74^a
BMI (kg/m²)	22.03±2.80	22.40±2.67	22.70±2.62^a	20.37±2.76^ab	23.26±2.01^b
FFM (kg)	54.01±7.95	54.84±7.09^a	56.66±7.09^b	46.70±7.06^abc	56.42±5.23^c
FM (kg)	14.79±5.69	15.58±5.71	13.67±5.89	15.72±5.71	17.72±4.51
Fat Mass (Percentage)	20.67±6.12	21.82±5.18	18.98±6.80^ab	24.79±5.41^a	23.70±4.43^b
CD4 Cells per uL	328±191	309±204	306±157	402±231
Viral Load (Log Copies per ml)	3.33±1.14	3.22±1.29	3.27±1.11	3.61±1.03
Dietary Intake (kJ)*	10,709±2,486	10,713±2,535	11,108±2,631	10,060±2,131
Dietary Intake (Percentage of Estimated Requirements HBE)	116.1±26.3	115.6±28.8	116.3±29.3	116.3±18.4

^a-d Values with the same superscript are significantly different (one-way ANOVA)
* Dietary intake comparison between the three groups adjusted for weight, height, age and activity level, using ANCOVA; P=0.437 between groups. Adjusted means for groups presented.

Table Three: A Comparison of Resting Energy Expenditure Measurements in HIV-Positive and Control Subjects

[Note: Due to the large size of the table; data for individual methods was not transferred from manuscript.]

Variable (Mean±SD)	HIV-Positive (N=70)	Weight Stable (N=23)	LD (N=30)	Weight Loss (N=17)	Control (N=16)
REE Measured, kJ (kcal)	7,201±1,226 (1,721±293)	7,535±1,205 (1,801±288)^a	7,489±1,054 (1,790±252)^b	6,247±1,092 (1,493±261)^ab	6,858±983 (1,639±235)
REE FFM, kJ/kg (kcal/kg)	134.80±15.09 (31.97±3.71)*	138.11±16.21 (33.01±3.87)^a	132.72±14.90 (31.74±3.63)	133.98±13.92 (32.07±3.30)	121.48±12.48 (29.04±2.98)^a
REE FFM + 11.90 kg, kJ/kg (kcal/kg)	109.84±12.08 (26.25±2.89)*	113.04±12.64 (27.02±3.02)^a	109.38±11.91 (26.14±2.85)	106.31±11.13 (25.41±2.66)	100.22±10.49 (23.96±2.51)^a
REE Adjusted for FFM⁺, kJ (kcal)	7,258±810 (1,735±194)*	7,460±886 (1,782±212)^a	7,222±826 (1,726±197)	7,046±642 (1,684±154)	6,617±695 (1,582±166)^a
REE Adjusted for FFM/FM⁺, kJ (kcal)	7,279±754 (1,740±180)*	7,454±765 (1,781±183)^a	7,370±778 (1,761±186)^b	6,899±631 (1,646±151)	6,501±645 (1,553±154)^ab

* HIV-positive group was significantly different from control group (P<0.05), using independent sample T-test
⁺ Assessed using analysis of covariance for all subjects combined. Presented both as the value adjusted for FFM in kJ and by adding the value of y at the x intercept (11.90kg), in order to adjuste for the non-zero intercepts and the value adjusted, using ANCOVA.
^a-b Values with the same superscript are significantly different.

Other Findings

17 HIV-positive subjects had documented weight loss (mean 7.17±3.61kg)
30 HIV-positive subjects reported lipodystrophy. This was supported by a higher waist-to-hip ratio (0.95±0.07 vs. 0.89±0.13, P=0.03) in those reporting lipodystrophy.
Fasting cholesterol (5.9±1 vs. 5.5±1.1mmol per L, P=0.012) and triglycerides (4.0±6.3 vs. 1.8±1.0mmol per L, P=0.047) were significantly higher in those reporting lipodystrophy
All subjects reporting LD had previously taken or were currently taking a protease inhibitor for more than six months
Of those reporting lipodystrophy, 11 reported lipoatrophy alone, four reported visceral adiposity alone and 15 reported both lipoatrophy and visceral adiposity. The emaining 23 subjects were body contour (self-report) and weight-stable
Differences in activity level and the proportion of patients using HAART were not significantly different between the three HIV-positive groups
Measured REE was not significantly different between the group of HIV-positive (1,721±293kcal) and control subjects (1,639±235kcal; P=0.299)
Within HIV-positive subjects, those with weight loss (1,493±261kcal) had a significantly lower measured absolute REE than the weight-stable (1,801±288kcal) and LD (1,790±252kcal) groups
All the prediction equations used gave an estimated value for REE which was significantly different from the measured value for the HIV-positive subjects

HBE bias: -519±828kJ, P<0.001
SE bias: -305±870kJ, P=0.005
CE bias: -807±828kJ, P<0.001
M91 bias: +925±820kJ, P<0.001
M93 bias: +774±816kJ, P<0.001.

The bias for REE, estimated using the HBE, was statistically significant in the control subjects (+360±653kJ, P=0.044)
When the absolute REE was expressed as a ratio to the predicted REE, HIV-positive subjects had significantly higher observed-to-predicted REE
Comparison of predicted vs. measured energy expenditure indicated that the weight-stable and LD HIV-positive groups were hypermetabolic, compared with the weight-losing HIV-positive group and controls
No statistically significant differences existed within the HIV-positive subjects when the lipodystrophy subdivisions were included (i.e., weight-stable, weight-loss, lipoatrophy, visceral adiposity and mixed syndrome, P>0.05)
Absolute REE correlated with FFM (R=0.750, P<0.001) and FM (R=0.425, P<0.001), but not with percentage fat mass (R=0.0932, P=0.443)
REE per kg FFM correlated with VL (R=0.2462, P=0.05)

REE adjusted for FFM tended to correlate with VL (R=0.239, P=0.060)
The significance decreased when the partial correlation accounted for both fat-free and fat mass (R=0.206, P=0.107).

REE (absolute or adjusted for FFM and FM) did not correlate with age or CD4 count
In the regression model, which included confounding variables, only FFM (P<0.001) and FM (P=0.001) were significantly associated with REE

REE (kJ)=912+102 FFM+57 FM
The standard error of the estimate was 757.29kJ, with an R² of 63.0% and an adjusted R² value of 61.9%.

Author Conclusion:

Main findings were that the existing published prediction equations for estimating energy expenditure were not accurate for estimating REE in HIV-positive men in the HAART era
Our results show that REE, adjusted for body composition, is not elevated in HIV-positive subjects with lipodystrophy (when the groups were pooled), when compared with HIV-positive subjects without the syndrome
The lack of a formal definition of lipodystrophy and differences in the recruitment criteria and body composition methodology may explain the differences in the results between this study and others
The etiology of this hypermetabolism requires investigation, preferably in a longitudinal study
Heterogeneity in body composition within subgroups of HIV-infected men made standard prediction equations for estimating REE invalid in this patient group. Prediction equations taking into account the body composition are recommended for use in HIV-positive subjects.

Funding Source:

Reviewer Comments:

Author Limitations

Unable to reliably establish the independent effect of HAART use, as only eight of the HIV-positive subjects were not taking HAART therapy
Use of bioelectrical impedance.

Limitations from Reviewer

No dietary intake information for controls.

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?	Yes
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.)	Yes
	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?	N/A
	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%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	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?	Yes
	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?	N/A
	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?	N/A
	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