H/A: Body Composition Measurement (2009)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To compare total and regional body composition in HIV-positive men and women according to highly active antiretroviral therapy (HAART), as well as the duration of HAART and its association with body composition.

Inclusion Criteria:
  • English-speaking
  • HIV-seropositive men and women
  • Age older than 18 years.
Exclusion Criteria:

Subjects without dual-energy x-ray absorptiometry DXA scans available.

Description of Study Protocol:

Recruitment

Subjects studied were enrolled in a longitudinal study (Nutrition for Healthy Living), which began in February 1995. Subjects were recruited through postings in hospitals, health centers and community centers that serve the HIV-positive population; through community outreach education programs; and by participant referral.

Design

Cross-sectional analysis of a cohort.

Statistical Analysis

  • Patients were classified by the medication regimen reported at the time of their DXA scan
  • Body composition was compared by Student's t test, Kruskal-Wallis test or chi-square test as appropriate between those reporting HAART use and those not reporting HAART
  • Two-factor analysis of variance determined that no interaction existed between sex and HAART use or duration
  • With use of general linear regression models, adjustments were made for age, participation in strength training, duration of HAART use, race, body mass index (BMI), and total body weight or total body fat
  • Specific medications taken at the time of the DXA scan were also examined for effects on regional fat mass, with adjustments made for age, participation in strength training and BMI.
Data Collection Summary:

Timing of Measurements

  • On enrollment in the study, medication history for the previous 12 months was determined by patient recall
  • Subjects were telephoned monthly to track subsequent changes in medication and health status
  • Subjects were seen monthly for two baseline appointments, then biannually for the remainder of the study
  • Starting in 1997, total and regional body composition was measured on all subjects at specified visits.

Dependent Variables

Total and regional body composition measured by DXA.

Independent Variables

  • HIV infection, CD4 count and HIV RNA 
  • Medication and health history collected by interviewer-administered questionnaires
  • Antiretroviral drug regimens reported at each visit were classified as HAART or non-HAART
  • HAART regimens included
    1. Two protease inhibitors
    2. Two nucleoside reverse transcriptase inhibitors with one protease inhibitor, or
    3. Two nucleoside reverse transcriptase inhibitors with one non-nucleoside reverse transcriptase inhibitor.

Control Variables

  • Age
  • Participation in strength-training
  • Duration of HAART use
  • Race
  • BMI
  • Total body weight
  • Total body fat.

 

Description of Actual Data Sample:

Initial N

265 HIV-positive subjects (203 men, 62 women) underwent a DXA scan before July 22, 1999.  

Attrition (final N)

As above.

Age and Ethnicity

Men, no HAART (n=65): Mean age, 42.1±7.8 years; 26 black, 30 white, five Hispanic, fou other

Men, HAART (n=138): Mean age, 43.2±7.0 years, 17 black, 105 white, seven Hispanic, nine other

Women, no HAART (n=27): Mean age, 39.0±5.0 years, 15 black, eight white, two Hispanic, two other

Women, HAART (n=35): Mean age, 39.4±7.7 years; 17 black, 14 white, four Hispanic, zero other.

Other Relevant Demographics

Men, no HAART (n=65): Mean CD4+,399.7x103cells per L±206.7x103cells per L; median HIV RNA 3.5x103log10copies per L 

Men, HAART (n=138): Mean CD4+, 409.7x103cells per L±266.7x103cells per L; median HIV RNA 2.7x103log10copies per L 

Women, no HAART (n=27): Mean CD4+, 489.2x103cells per L±414.1x103cells per L; median HIV RNA 3.5x103log10copies per L 

Women, HAART (n=35): Mean CD4+, 434.7x103cells per L± 260.1x103cells per L; median HIV RNA 2.3x103log10copies per L.

Anthropometrics

Sex and race distributions of the populations studied were similar to those in the Massachusetts Department of Public Health AIDS surveillance data.

Location

Massachusetts.

Summary of Results:

 

Variable
Men, No HAART (n=65) Men, HAART (n=138) P-value Women, No HAART (n=27) Women, HAART (n=35) P-value
Unadjusted mean±SD
Unadjusted mean±SD

Weight (kg)

75.7±7.8 74.9±7.0 0.66 64.5±16.4 70.0±19.2 0.23
Percentage body fat (%) 21.9±7.6 20.0±7.5 0.09 32.6±9.8 34.8±12.3 0.44
Total fat mass (kg) 17.0±7.5 15.5±8.1 0.20 22.3±11.6 26.0±14.9 0.28
Total lean body mass (kg) 55.9±7.8 56.9±7.9 0.43 40.1±6.2 41.8±7.4 0.33
Total bone mineral content (kg) 2.8±0.05 2.5±0.04 0.001 2.2±0.03 2.2±0.04 0.67
Trunk fat mass (kg) 8.0±4.4 8.2±5.0 0.77 9.3±5.8 12.7±8.6 0.07
Trunk lean body mass (kg) 28.3±4.1 29.0±4.1 0.21 21.1±3.2 22.0±3.7 0.28
Trunk bone mineral content (g) 725±0.02 660±0.02 0.004 553±0.01 582±0.01 0.33
Appendicular fat mass (kg) 8.1±3.5 6.4±3.7 0.002 12.2±6.1 12.4±6.8 0.89
Appendicular lean body mass (kg) 23.1±4.1 24.2±39.6 0.72 15.9±3.2 16.5±3.7 0.48
Appendicular bone mineral content (g) 1,528±311 1,359±0.03 <0.001 1,110±0.02 1,110±0.02 0.86
Leg fat mass (kg) 6.2±0.3 4.7±2.9 0.001 9.5±5.0 9.2±5.1 0.82

Leg lean body mass (kg)

17.4±2.9

17.8±2.9

0.46 12.3±2.7 12.8±2.9

0.52

Leg bone mineral content (g) 1,109±0.02 989±0.02 <0.001 826±0.01 820±0.02 0.87

Other Findings

After adjustment for age, weight, race and exercise habits, total weight and fat mass did not differ significantly in men or women by HAART

Trunk fat was greater in men (1.0kg, P<0.001) and women (1.4kg, P=0.005) and leg fat was lower in men (-1.0kg, P<0.001) and women (-1.5kg, P=0.005) receiving HAART than in those not receiving HAART.

This corresponded to a greater percentage of total fat mass located in the trunk (men: 7.5%, P<0.001; women: 5.1%, P=0.02).

Lean mass was also greater with longer duration of HAART in men (P<0.002).

In men receiving HAART, total and regional bone mineral content were less than in the men not receiving HAART (P<0.001); these effects increased with longer duration of HAART.

Protease inhibitors were associated with the largest differences in regional fat.   

Author Conclusion:

HAART is associated with redistribution of fat mass from the legs to the trunk, despite no significant differences in total fat mass or weight. In men, HAART is also associated with a reduction in bone mineral content, suggesting that HAART increases the risk of central obesity and osteoporosis. The mechanism of the syndrome of central adiposity remains elusive. The major focus of studies of this syndrome has been abdominal adiposity, but our findings suggest that peripheral fat wasting, primarily in the legs; increases in lean mass; and decreases in bone mineral content are as strongly associated with HAART use in a diverse HIV-seropositive population. Thus, in future studies of this syndrome, it will be important to separately analyze arms and legs, as well as fat, lean and bone mass.

Funding Source:
Government: NIDDK grants P01-DK45734 and P30-DK46200, NIH grant M01-RR00054
Reviewer Comments:

Authors note the following limitations:

  • DXA was used as a compromise between more expensive imaging methods (such as magnetic resonance imaging and computed tomography) and less accurate methods (anthropometry and bioelectrical impedance). Use of  DXA for regional analysis has several limitations.
  • Results of the study do not prove causality by HAART regimens.
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) N/A
  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) N/A
 
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? 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? 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? 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? 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