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H/A: Caloric Needs (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
  • The primary aim of this study was, by conducting a meta-analysis combining previous research, to ascertain an overall mean difference in REE between HIV-positive subjects and healthy control subjects
  • Two secondary aims were to investigate variations in this mean difference between various clinical subgroups (e.g., persons with lipodystrophy, those who are losing weight, those who are symptomatic and those who are weight stable) and to investigate the effect of potential confounding covariates on that mean difference.
Inclusion Criteria:
  • Studies were conducted in humans
  • Subjects were adults
  • Subjects were measured after an overnight fast or under a strict post-prandial protocol (because diet-induced thermogenesis has been shown to be prolonged past 300 minutes in HIV-positive subjects)
  • Data on body composition were collected
  • Published in English.
Exclusion Criteria:
None.
Description of Study Protocol:

Recruitment

  • Medline, CINAHL, Current Contents Connect, HIV/AIDS database, Expanded Academic Index (from 1981, when AIDS was first described, to September 2004)
  • Search terms: Resting energy expenditure and HIV, resting metabolic rate and HIV, indirect calorimetry and HIV, fat oxidation and HIV.

Design

Meta-analysis.

Statistical Analysis

  • Crude, classical and Bayesian methods of meta-analysis were performed for comparison
  • Crude meta-analysis: To use all of the available data comparing HIV-positive subjects and healthy control subjects when estimates of variance were not provided, this analysis based on the method of Gotzsche was performed. Mean REE of each group was divided by the mean FFM of each group and that value then used to calculate an overall mean difference and 95% CIs.
  • Traditional meta-analysis: Classical framework, comparing REE divided by FFM (kJ per kg) in the HIV-positive and control groups and within the HIV subgroups. The random-effects model based on the method-of-moments estimator was used, with the inverse-variance fixed-effects model shown for comparison.
  • Bayesian random-effects method: Used to estimate the common effect and the between-study variance and to compare this estimate with the estimates obtained by using the method of DerSimonian and Laird. A mixed indirect comparison was performed, which allowed for the incorporation of all available information, regardless of whether there are data for all comparisons. The model was set up to compare the HIV subgroups (i.e., lipodystrophy, weight-losing, weight-stable and symptomatic), with healthy control subjects and within-group comparisons were also modeled.
  • An ancillary analysis was performed on the available individual data to obtain an estimate of REE, adjusted for FFM. This was conducted using the general linear model (analysis of covariance) in SPSS. Two models were employed:
    1. An analysis with HIV-positive or healthy control subjects as the factor
    2. An analysis considering the study site in addition to HIV status of the subject.
  • Heterogeneity was detected by visual inspection and by using chi-square test. Formal investigation of heterogeneity was performed by univariate metaregression with lipodystrophy, technique of body-composition measurement, use of HAART in the HIV-positive group and mean age of subjects as covariates.
  • Publication bias was assessed visually, by using a funnel plot that plots sample size against the treatment effect and that has a funnel shape when publication bias is not present. Formal testing was conducted by using the rank correlation test of Begg and Mazumdar, the regression test of Egger et al, and the "trim and fill" method of Duval and Tweedie (a non-parametric method that estimated the number of missing studies, along with mean and SE difference and then adds in the estimated values, recalculating the overal mean and SE.
  • Sensitivity analysis was conducted on the primary analysis.
Data Collection Summary:

Timing of Measurements

1981 to Sept 2004.

Dependent Variables

REE/FFM.

Independent Variables

  • HIV-symptomatic
  • Lipodystrophy
  • Weight-losing
  • Weight-stable
  • Healthy (HIV-) control.

Control Variables

  • Use of HAART
  • Method of body-composition measurement
  • Age.
Description of Actual Data Sample:

Initial N

  • 58 studies
  • 32 included an HIV-negative control group and they were considered for the primary analysis. 26 of these studies were used to calculate the crude effect estimate. Inclusion of both an estimate and SD or SE allowed formal statistical analysis of 24 studies.
  • Individual data were available for 21 studies, nine of which included a control group. 785 HIV-positive subjects and 403 healthy control subjects.
  • Data were available from only two studies that included groups of HIV-positive subjects without lipodystrophy, who were receiving and not receiving HAART.

Age

Adult studies.

Location

Worldwide studies.

Summary of Results:

Other Findings

  • The mean effect size and 95% CIs for the difference between HIV-positive and healthy control subjects was 11.02kJ per kg FFM (95% CI: 8.03, 14.01)
  • All analyses indicated that REE/FFM was significantly higher in HIV-positive subjects than in healthy control subjects
  • The use of the random-effects classical estimate of the overall mean difference (11.93kJ per kg) and multiplication of that number by the mean FFM in the HIV-positive groups (53kg) gives a daily difference in energy expenditure between HIV-positive and control subjects of approximately 630kJ (classical estimate) or approximately 661kJ (Bayesian random-effects estimate based on the T distribution (12.47kJ per kg). This difference reflects an elevation in REE of approximately 9% when the mean REE/FFM for HIV-positive subjects is divided by the REE/FFM for control subjects.
  • The test for heterogeneity was significant (chi-square=88.73, df=23, P<0.001) and the proportion of variability in the mean difference, due to heterogeneity rather than to sampling error, was 74%
  • Within the HIV-positive subgroups, there was a trend toward higher REE/FFM in the symptomatic subjects than in the weight-stable subjects (P=0.079)
  • All HIV subgroups showed significantly higher REE/FFM than was seen in the control subjects
    • Symptomatic subjects: P=0.012
    • Weight-losing subjects: P=0.020
    • Subjects with lipodystrophy: P<0.001
    • Weight-stable subjects: P<0.001.
  • No significant difference between HIV-positive subjects with lipodystrophy and weight-stable HIV-positive subjects without lipodystrophy
  • Lipodystrophy, method of body-composition measurement, subject age and HAART usage in the HIV-positive group were unable to explain the heterogeneity by using metaregression in either a classical or Bayesian framework
  • The studies in which the subjects were using HAART had an overall mean difference in REE of 15.10kJ per kg FFM, compared with healthy controls, whereas the studies in which the HIV-positive subjects were not using HAART showed a mean difference of 11.02kJ per kg FFM, which equates to an estimated difference of 216kJ per day. No significant difference in metaregression.
Author Conclusion:
  • Overall REE/FFM is higher in HIV-positive subjects than in healthy controls by an estimated 630kJ to 661kJ per day or approximately 9%
  • Within the HIV-positive population, there is evidence that persons with symptomatic infection have significantly higher REE/FFM than do other HIV-positive persons, possibly contributing to the variations reported in the literature. However, further studies are required to confirm these subgroup analyses.
  • The research published to date suggests that REE/FFM in persons with lipodystrophy does not differ significantly from that in other weight-stable HIV-positive persons.
Funding Source:
Reviewer Comments:

Limitations as cited by authors:

  • Number of studies including subjects symptomatic for AIDS was too small to investigate in formal analyses using metaregression
  • Differences in antiretroviral regimens, mean subject ages and other patient factors that are related to lipodystrophy could not be considered in this subanalysis because of the small sample size
  • Definitions of lipodystrophy in the various studies differed
  • Validity of bioelectrical impedance analysis in subjects with lipodystrophy has been challenged and the sample size did not allow a metaregression on the effect of body-composition measurement methods in the lipodystrophy studies alone
  • Only five studies included subjects with HAART.
Quality Criteria Checklist: Review Articles
Relevance Questions
  1. Will the answer if true, have a direct bearing on the health of patients? Yes
  2. Is the outcome or topic something that patients/clients/population groups would care about? Yes
  3. Is the problem addressed in the review one that is relevant to dietetics practice? Yes
  4. Will the information, if true, require a change in practice? Yes
 
Validity Questions
  1. Was the question for the review clearly focused and appropriate? Yes
  2. Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described? Yes
  3. Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased? Yes
  4. Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible? Yes
  5. Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined? Yes
  6. Was the outcome of interest clearly indicated? Were other potential harms and benefits considered? Yes
  7. Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described? Yes
  8. Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included? Yes
  9. Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed? Yes
  10. Was bias due to the review's funding or sponsorship unlikely? Yes