- Click here for explanation of classification scheme.

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.

HIV-infected and HIV-seronegative men and women

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)

Recruitment

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.

Design

Case-control

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.

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.

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)

None

Age

Ranged from 38 to years of age

Ethnicity

Not listed

Other relevant demographics

None listed

Anthropometrics

• 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

Location

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

 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	82±8	69±17	65±18*
VAT/TAT, percentage	18±8	31±17	35±18

*P<0.05.

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	4.8±5.4	8.5±5.2
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 

• 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.

Government:

NIH

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.