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H/A: Physical Activity (2009)

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

The purpose of this study was to examine relationships between lipolysis and fatty acid (FA) oxidation during rest, moderate exercise and recovery, and measures of insulin sensitivity or glucose tolerance and fat redistribution in HIV-positive subjects taking RTV, HAART but no PI and HIV-seronegative controls.

Inclusion Criteria:

HIV-infected and HIV-seronegative men and women

Exclusion Criteria:

Taking medications or dietary supplements that affect lipid or glucose metabolism or peak heart rate (i.e. statin, fibrate, sulfonylurea, corticosteroids and beta-adrenergic blockers)

Description of Study Protocol:


HIV-infected and HIV-seronegative men and women were recruited from the AIDS Clinical Trials Unit, the Infectious Disease Clinics, and the Volunteers for Health Program at Washington University School of Medicine and from the surrounding community.



Blinding used (if applicable)

Implied for laboratory measures

Intervention (if applicable)

Comparison groups were:

  1. HIV-seropositive subjects presently taking HAART, including the PI RTV (HIV + RTV)
  2. HIV-seropositive subjects taking HAART, not including a PI (HIV+ No PI)
  3. HIV-serognegative controls matched for age, gender and activity level.

Statistical Analysis

  • Pearson product moment correlations were used to evaluate relationships between descriptive and physiological variables
  • One-way ANOVA with Tukey honestly significant differences post-hoc tests were used to compare descriptive peak aerobic fitness and body composition parameters among groups
  • Two-way ANOVA (group x condition) with repeated measures and Tukey HSD were used to compare substrate kinetics and hormone concentrations among groups during each condition (i.e., rest, exercise and recovery)
  • Confounding variables identified through Pearson product moment correlation were statistically controlled for by means of analyses of covariance
  • A P-value ≤0.05 was considered statistically significant
  • All data are expressed as means ± SD unless specified otherwise.
Data Collection Summary:

Timing of Measurements

  • Date(s) of study conducted not given
  • Cross-sectional except for the exercise portion which was conducted at rest, during exercise and during recovery after exercise.

Dependent Variables

  • Body composition: Whole body, trunk and limb fat mass (FM) and fat-free mass (FFM) were quantified using a Hologic Discovery enhanced-array dual-energy X-ray absorptiometer (DEXA). Fat distribution was described as a ration of trunk FM to limb FM. Thigh subcutaneous fat and abdominal [subcutaneous (SAT) and visceral adipose tissue (VAT)] fat areas were quantified using proton magnetic resonance imaging. Total abdominal adipose tissue was calculated as the sum of SAT and VAT.
  • Serum metabolic and endocrine parameters
  • Lipid kinetics: Standardized meal containing 12kcal/kg body weight and 55% carbohydrate, 30% fat and 15% protein at 1,800 hours. At 1,900, subjects ingested a high-carbohydrate liquid beverage (80g carbohydrates, 12.2g fat, 17.6g protein; Ensure) to ensure adequate muscle and hepatic glycogen stores. Subjects then fasted overnight and until completion of the study the following day. Isotopic infusions of NaH13CO2 and [1-13C]palmitate at 06:00 followed by beginning of exercise testing at 09:00. Blood samples were measured for glycerol and palmitate tracer-to-trace ratios (TTRs) and plasma substrate and hormone concentrations.

Independent Variables 

  • HIV-seropositive subjects presently taking HAART, including the PI RTV (HIV + RTV)
  • HIV-seropositive subjects taking HAART, not including a PI (HIV+ No PI)
  • HIV-serognegative controls matched for age, gender and activity level.

Control Variables

Confounding variables identified through Pearson product moment correlation were statistically controlled for by means of analyses of covariances.

Description of Actual Data Sample:

Initial N

  • 32 men and women
  • 10 (two women) in HIV seronegative; 10 (two women) in HIV + No PI; 12 (two women) in HIV + RTV

Attrition (final N)



Ranged from 38 to years of age


Not listed

Other relevant demographics

None listed


  • BMI (kg/m2): HIV seronegative 25.7±3.4; HIV + No PI 24.7±4.2; HIV + RTV 27.1±5
  • Resting EE (kcal per minute): HIV seronegative 1.1±0.2; HIV + No PI 1.2±0.2; HIV + RTV 1.2±0.2
  • Peak VO2 (mL*kg-1*minimum-1): HIV seronegative 33.1±9.7; HIV + No PI 27.7±6.0; HIV + RTV 26.4±5.4


AIDS Clinical Trials Unit, the Infectious Disease Clinics and the Volunteers for Health Program at Washington University School of Medicine and from the surrounding community

Summary of Results:

 Table 2. Body composition parameters (significant differences only)

Variable HIV Seronegative HIV+No PI HIV+RTV
Trunk/limb ratio 0.9±0.2 1.4±0.6 1.6±0.8*

SAT/TAT, percentage


69±17 65±18*

VAT/TAT, percentage


31±17 35±18


Table 4. Metabolic and endocrine parameters during rest, exercise and recovery (significant differences only)

Variable HIV Seronegative HIV+No PI HIV+RTV
Insulin, uU/ml      
 70-minute exercise 4.6±2.3


 60-minute recovery 3.8±2.1 6.0±6.8 9.2±6.6
Epinephrine, pM      
 70-minute exercise  125.9±58.6* 103.3±49.6*  145.3±142.2* 
 60-minute recovery  45.2±24.1*** 33.8±29.9*** 62.5±62.4*** 
Norepinephrine, nM      
 70-minute exercise 737.6±258.1   578.4±255.7* 747.1±462.1* 
 60-minute recovery  192.0±52.2*** 167.8±68.1***   302.6±167.4***
Lactate, umol/L      
 70-minute exercise  1,396±824.2 946.4±1,141.8* 2,307.9±1,337.6* 

*P<0.05 rest to exercise; **P<0.02 vs. HIV + No PI and Control; ***P<0.05 exercise to recovery.

 Other Findings

  • No significant differences in body mass index, FFM total body FM, limb and trunk FMs (DEXA), thigh and subcutaneous fat (MRI), and IMCL, extramyocellular lipid content and liver fat content among groups
  • HIV + RTV had significantly greater trunk fat-to-limb fat ratio (Table 2), greater trunk fat as a percentage of total FM (Control: 47±5%; HIV + No PI 57±9%; HIV + RTV: 58±11%; P<0.05), a significantly greater percentage of VAT to TAT (Table 2), significantly lower limb fat as a percentage of total fat (Control: 53±5%; HIV + No PI: 43±9%; HIV ± RTV: 43±11%, P<0.05), and SAT/TAT than Control (Table 2).
  • HIV + No PI had a trend toward greater trunk fat-to-total fat (P<0.97) and significantly lower limb fat-to-total fat ratio (P<0.05) compared with Control but were not different than HIV + RTV
  • VO2 peak was not different among the groups; however, HIV-positive subjects had an 18% lower peak than Controls (P<0.03; data was not included)
  • At rest, no significant differences in glucose, insulin, C-peptide, FFA, epinephrine, norepinephrine or energy expenditure between groups
  • HIV-positive subjects tended (P=0.12; data was not included) to have higher insulin levels than Controls
  • HIV + RTV but not HIV + No PI tended to have greater serum TG and lower HDL and LDL than Control
  • In HIV +RTV, insulin levels were lower during exercise than at rest but did not change in the other groups (Table 4)
  • Epinephrine and norepinephrine levels increased in all groups during exercise
  • Blood lactate levels during exercise increased more in both HIV-positive groups than in the Control group (Table 4)
  • FFA levels increased from rest to sub-maximal exercise in Control, but not in either HIV-infected group
  • No significant differences in glucose, insulin, C-peptide, epinephrine or norepinephrine were observed between groups during exercise
  • During recovery from exercise, epinephrine and norepinephrine returned to baseline levels in all groups. Blood lactate also returned to baseline levels in both HIV-infected groups. Insulin and C-peptide during recovery were greater in HIV + RTV than HIV + No PI and Control.
  • The glycerol rate of appearance was not different among groups during rest or recovery; however, the increase in appearance during exercise was less in both HIV + RTV and HIV + No PI compared with Control. The rate of appearance for palmitate followed a similar trend to glycerol. 
  • During exercise, Control subjects had increased palmitate, FFA and total FA oxidation rates (~50%) and these returned to resting levels after 60-minute recovery. This pattern was also seen in both HIV-infected groups. The magnitude of increase in palmitate and plasma FA oxidation rates during exercise was less in the HIV-infected groups.
  • No difference among groups for the average percent palmitate uptake oxidized among groups during any condition
  • Lower lipolytic rates during exercise were not associated with lower limb or trunk fat as measured by DEXA or lower SAT or VAT as measured by MRI
  • Glycerol rate of appearance was correlated with plasma FA oxidation (r=0.86, P<0.001)
  • No significant correlations between substrate kinetics and measures of insulin resistance or glucose tolerance during any condition 
Author Conclusion:
  • Patients with well-controlled HIV infection receiving HAART had a markedly blunted ability to oxidize FA during exercise at an intensity that corresponds to instrumental activities of daily living
  • Defects in FA oxidation were primarily due to decreased FFA delivery and a lesser contribution from impaired intramuscular TG oxidation
  • Further investigations into adipose tissue depot-specific responses to exercise-induced lipolysis and FA oxidation in HIV-positive subjects taking HAART are warranted.
Funding Source:
Government: NIH
Reviewer Comments:

Low numbers of women to men in each group (only two per group). Is there a difference in lipid metabolism between men and women, especially with HIV infection? This study could not address this to low sample size.

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.) No
  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? N/A
  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? ???
  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? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? Yes
  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? Yes
  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)? No
  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