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Effects of High-Intensity Endurance and Resistance Exercise on HIV Metabolic Abnormalities: A Pilot Study F. Patrick Robinson, Lauretta T. Quinn and James H. Rimmer Biol Res Nurs 2007; 8; 177 DOI: 10.1177/1099800406295520 The online version of this article can be found at: http://brn.sagepub.com/cgi/content/abstract/8/3/177

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Effects of High-Intensity Endurance and Resistance Exercise on HIV Metabolic Abnormalities: A Pilot Study F. Patrick Robinson, PhD, RN, ACRN Lauretta T. Quinn, PhD, RN James H. Rimmer, PhD

(±69.88), and insulin sensitivity decreased by 15.7% (±41.7%), neither of which was a statistically significant change. Results suggest that further testing of the combined exercise intervention in a randomized controlled design is warranted.

The purposes of this pilot study were to examine the effects of a 16-week supervised high-intensity combined endurance and resistance exercise training program on HIV-associated metabolic abnormalities (abdominal adiposity, dyslipidemia, and insulin resistance) and to explore methodological issues related to the design and implementation of the research protocol in preparation for a randomized controlled trial. A one-group pretest-posttest design was used, with outcomes measured at baseline and within 1 week after the conclusion of the training program. The exercise program consisted of 16 weeks (preceded by a 2-week phase-in period) of three endurance sessions (20 min at 70%-80% of VO2max) and two resistance sessions per week (one set of 8-10 repetitions at 80% of one-repetition maximum on seven exercises). Outcome measures included lipid levels (total, high-density lipoprotein, and lowdensity lipoprotein cholesterol and triglycerides), visceral and subcutaneous adipose area measured by electron beam tomography, fat and lean mass of trunk and limbs measured by dual-energy X-ray absorptiometry, and insulin sensitivity measured by the homeostatic model assessment. Nine participants were recruited, 5 of whom completed the intervention and had pretest and posttest data available for analyses. Aerobic capacity and strength improved over the course of the intervention. Statistically significant decreases were found for total and trunk fat mass (1,324.9 g [±733.6] and 992.8 g [±733.6], respectively). Triglycerides decreased by 59 mg/dL

F. Patrick Robinson, PhD, RN, ACRN, is an assistant professor at the University of Illinois at Chicago, College of Nursing, Department of Medical-Surgical Nursing. Lauretta T. Quinn, PhD, RN, is an associate professor at the University of Illinois at Chicago, College of Nursing, Department of Medical-Surgical Nursing. James H. Rimmer, PhD, is a professor at the University of Illinois at Chicago College of Applied Health Sciences, Department of Disability and Human Development. Address for correspondence: F. Patrick Robinson, PhD, RN, ACRN, University of Illinois at Chicago College of Nursing, Department of MedicalSurgical Nursing (M/C 802), 845 South Damen Avenue, Room 758, Chicago, IL 60612; e-mail: [email protected].

BIOLOGICAL RESEARCH FOR NURSING Vol. 8, No. 3, January 2007, 177-185 DOI: 10.1177/1099800406295520 Copyright © 2007 Sage Publications

This study was supported by grants from the Honor Society of Nursing Sigma Theta Tau International and the American Nurses Foundation/Hyundai Motors America. The authors wish to thank Kevin Grandfield for editorial assistance.

Key words: HIV, exercise, lipids, metabolism, lipodystrophy, adiposity, insulin resistance

Highly active antiretroviral therapy (HAART), while producing dramatic and sustained suppression of viral replication, improved immune function, and reduced morbidity and mortality (Palella et al., 1998, 2004), has also been associated with metabolic changes (increased abdominal adiposity, dyslipidemia, and insulin resistance) that may increase risk for cardiovascular disease (CVD; Grinspoon, 2005; Grinspoon


178 BIOLOGICAL RESEARCH FOR NURSING Vol. 8, No. 3, January 2007

& Carr, 2005; Robinson, 2004; Shlay et al., 2005). The link between HAART and metabolic abnormalities is unclear and may be a direct result of drug toxicity, immune reconstitution, or longer term survival. Furthermore, HIV itself likely contributes to the etiology of metabolic abnormalities (El-Sadr et al., 2005). Although a matter of concern, existing data do not suggest that the risks of antiretroviral therapy outweigh the benefits. Much to the contrary, disability and death are the highly probable outcomes of untreated HIV infection, whereas the risk of CVD remains small (Bozzette, Ake, Tam, Chang, & Louis, 2003). However, the pathogenesis of CVD occurs over decades, and the current HIV-infected population has been exposed to HAART for a relatively short duration. Longer survival coupled with a high prevalence of traditional CVD risk factors in this same population (age, gender, smoking; Hadigan et al., 2001; Riddler et al., 2003) will likely increase the incidence of CVD associated with HIV disease. Pharmacological interventions, including the use of certain statins, fibrates, metformin, and thiazolidinediones, are commonly used to manage dyslipidemia and glucose intolerance within the context of HIV disease (Hadigan et al., 2000; Visnegarwala et al., 2004). Although data suggest that these pharmacological agents are safe and modestly effective, they are not without side effects and potential toxicities. Moreover, some patients on HAART must follow complex drug regimens; adding more medications increases patient burden and the likelihood of nonadherence. Investigation into lifestyle/behavioral changes that may ameliorate metabolic abnormalities in HIV is therefore needed to reduce CVD risk while avoiding the use of CVD medications. Participation in regular moderate- to high-intensity exercise may prove to be an effective first-line treatment strategy for HIV metabolic abnormalities. Clinical and epidemiological research suggests that increased physical activity is associated with improved lipid levels, glucose tolerance, and insulin sensitivity, along with decreased adiposity (Buemann & Tremblay, 1996; Durstine et al., 2001; Ivy, 1997; Ross, Freeman, & Janssen, 2000). Various groups have investigated exercise as a first-line treatment for HIV-related metabolic abnormalities. Endurance or resistance training alone has produced decreases in triglycerides (Thoni et al., 2002; Yarasheski et al., 2001) and reductions in indices of adiposity (Roubenoff, McDermott, et al., 1999; Smith et al., 2001; Thoni et al., 2002).

Likewise, in small, uncontrolled studies, combined endurance and resistance training has been shown to reduce triglyceride levels and trunk adiposity (Jones, Doran, Leatt, Maher, & Pirmohamed, 2001; Roubenoff, Weiss, et al., 1999). The purposes of this pilot study for a randomized controlled trial were to determine the effects of high-intensity endurance and resistance training on HIV-associated fat redistribution, dyslipidemia, and insulin resistance and to explore methodological issues related to the design and implementation of the protocol.

Methods Design A one-group pretest-posttest design was used with outcome variables measured at baseline and at the conclusion of a 16-week combined endurance and resistance exercise intervention. Outcome variables were measured the week prior to the start of the phase-in period and during the week following the last exercise session. Sample A convenience sample that met the following criteria was recruited: (a) HIV seropositive, (b) treatment with a HAART regimen for at least 24 months, (c) CD4+ lymphocyte number ≥100 cells/mm3, (d) viral load ≤150 000 copies/mm3, (e) aged 30 to 55 years, (f) sedentary (i.e., exercising ≤1 time per week for ≤15 min), (g) evidence of abdominal adipose tissue accumulation using the HIV Outpatient Study cohort assessment (Lichtenstein et al., 2001), and (h) willing and able to exercise 3 days a week. Exclusion criteria included (a) use of lipid-lowering, insulin-sensitizing, or hypoglycemic drugs, anabolic steroids, growth hormone, or megestrol acetate (must be off drug for at least 4 weeks before study entry); (b) current opportunistic infection; (c) diagnosis of diabetes mellitus or coronary artery disease; and (d) orthopedic, muscular, or joint problem that would prevent exercise. Exercise Intervention Individuals participated in a 16-week structured endurance and resistance exercise program consisting of 3 supervised sessions per week (48 sessions). All training sessions took place at a research fitness center


Robinson et al. / Exercise in HIV 179 Table 1. Week

Exercise Intervention Prescription Sessions/Week

Session

–1

3

0

3

1-16

3

1 2 3 1 2 3 1, 2 3

Endurance

Resistance 6-8 repetitions at 60% of 1-RM 8-10 repetitions at 60% of 1-RM

15 min at 50%-60% of VO2max 20 min at 50%-60% of VO2max 20 min at 50%-60% of VO2max 20 min at 60%-70% of VO2max 20 min at 60%-70% of VO2max 20 min at 60%-70% of VO2max 20 min at 70%-80% of VO2max 20 min at 70%-80% of VO2max

6-8 repetitions at 70% of 1-RM 8-10 repetitions at 70% of 1-RM 8-10 repetitions at 80% of 1-RM

NOTE: Weeks –1 and 0 represent a 2-week phase-in period. Weeks 1 to 16 represent the intervention. 1-RM = one-repetition maximum.

Table 2.

Resistance Exercises With Muscles Affected

Exercise Upper body Lat pull down Seated row Shoulder press Bench press Lower body Leg press Calf press Seated leg curl

Primary Muscles

Secondary Muscles

Latissimus dorsi Latissimus dorsi, rhomboids Ant deltoids Pectoralis major

Biceps Trapezius, post deltoids, teres minor, teres major, biceps Med deltoids, triceps Ant deltoids, triceps

Quadriceps Gastrocnemius Hamstrings

Gluteus, hamstrings

under the supervision of a certified exercise specialist. A schema of the intervention is presented in Table 1. Each week contained three endurance training sessions consisting of 5-min warm-up and cool-down periods and a 20-min brisk walk, jog, or run on a treadmill to maintain effort at 70% to 80% of maximal oxygen uptake (VO2max). VO2max was measured via open-circuit spirometry during a maximal exercise test on a treadmill according to American College of Sports Medicine Guidelines (Franklin, 2000) using a modified Bruce protocol (Franklin, 2000). The 70% to 80% VO2max corresponded to a target heart rate (HR) range (determined by the observed HR at VO2max during the maximal exercise test). This prescribed intensity is labeled high (American College of Sports Medicine & Roitman, 2001). HR was monitored during each session with a heart rate monitor (chest-band transmitter and wristwatch display). Two of the three endurance sessions were followed immediately by dynamic resistance training sessions consisting of one set of 8 to 10 repetitions for seven exercises (four upper body and three lower body) performed on stacked-weight machines at an intensity of 80% of one maximal repetition (1-RM; the maximal weight that can be lifted in proper form one

time for a specific exercise). Descriptions of each resistance exercise and the affected muscle groups are contained in Table 2. The 1-RM testing was conducted by a certified exercise specialist and retested at the midpoint of the intervention (Week 8), and weight was adjusted to maintain the resistance at 80%. Preceding the actual 16-week intervention was a 2-week graded phase-in period during which participants increased the intensity and duration of exercises to reach the desired prescription by the end of the 2nd week. The purpose of the phase-in period was to allow participants to acclimate gradually to the exercise prescription. The phase-in period followed the same schedule as the intervention. A high-intensity endurance prescription was chosen because it has been shown to positively effect dyslipidemia (Durstine et al., 2001) in non-HIV-infected samples. It is not known whether the same is true in HIV, so this prescription seemed logical for pilot work. In regard to the resistance prescription, cumulative evidence suggests that there is little difference in strength gain or muscle hypertrophy between training with one versus multiple sets of repetitions (Carpinelli & Otto, 1998). One set has the added benefit of time efficiency. Published exercise studies that investigated


180 BIOLOGICAL RESEARCH FOR NURSING Vol. 8, No. 3, January 2007

HIV-related metabolic abnormalities reported positive effects around 12 weeks. Therefore, a 16-week time frame was chosen to determine additional gains. Outcome Variables Fat Area Visceral and subcutaneous fat areas were measured by electron beam tomography (EBT) with a GE Imatron-150 EBT scanner (GE Imatron, South San Francisco, CA). Participants were examined in the supine position with both arms stretched above the head. The scan was performed at the L4-L5 vertebrae level using a scout image of the body to establish the precise scanning position (DeNino et al., 2001; Poehlman, Dvorak, DeNino, Brochu, & Ades, 2000). This position encompasses the largest percentage of fat in the body and best allows differentiation of visceral from subcutaneous fat (Borkan et al., 1982). A single 3or 6-mm slice was taken during suspended respiration after a normal expiration. After the acquisition, the scan was transferred to an AccuImage image analysis workstation where abdominal adipose tissue areas were measured using the AccuAnalyzer module. Total abdominal fat was calculated by delineating the body surface with a stylus and then computing the adipose tissue surfaces with an attenuation range of –190 to –30 Hounsfield units (DeNino et al., 2001; Poehlman et al., 2000). The visceral fat area was quantified by delineating with a stylus the abdominal cavity at the internal-most aspect of the abdominal wall (transversalis fascia) and the posterior aspect of the vertebral body. The subcutaneous fat area was calculated by subtracting the visceral area from the total area. Determination of visceral fat from a single scan at L4-L5 is highly correlated to total visceral fat volume in both genders (Kvist, Chowdhury, Grangard, Tylen, & Sjostrom, 1988). Excellent reproducibility of fat measurements using this technique was shown by a high correlation between duplicate measurements (r = .99) and by small precision errors: 1.2% for total, 1.9% for subcutaneous, and 3.9% visceral (Thaete, Colberg, Burke, & Kelley, 1995). Fat Mass Total, trunk, and limb fat and fat-free masses were determined from the whole-body dual-energy X-ray absorptiometry (DXA) scan, which uses a threecompartment model: (a) whole-body fat mass, (b) whole-body bone-free lean tissue mass, and (c)

whole-body bone mass. Regions of interest were delineated using a stylus. At tissue thickness ranging from 5 to 25 cm, errors in measurement of fat for whole-body scans were less than 3% (Blake, Wahner, & Fogelman, 1999). The standard errors for the measurement of body composition are 1.9 kg for fat mass and 2.7 kg for lean body mass (Blake et al., 1999). The short-term precision (coefficient of variation %) of DXA in adults has been reported as 4.9% for fat, 4.6% for fat mass, and 1.5% for lean body mass (Blake et al., 1999). Although not yet a gold standard, there is good agreement between DXA measurement of body composition and other methods, such as underwater weighing and densitometry (Pritchard et al., 1993; Wang et al., 1996; Wellens et al., 1994). Lipid Levels Lipid levels were measured from fasting sera by standard clinical laboratory procedures. Analyses were performed in a Clinical Laboratory Improvement Amendments–certified laboratory. The triglyceride levels were determined using the glycerol kinase/peroxidase technique. High-density lipoprotein and lowdensity lipoprotein (LDL) cholesterol were determined using dextran sulfate precipitation oxidase and enzymatic techniques, respectively. Insulin Sensitivity The homeostatic model assessment (HOMA; Matthews et al., 1985) was used to yield an estimate of insulin sensitivity from one-time fasting plasma insulin (determined via chemiluminescent immunoassay) and glucose (determined via hexokinase spectrophotometry) concentrations. The predictions used in the model arise from experimental data in humans and animals. The equation for percentage sensitivity is S% = (FPI × FPG)/22.5 and for percentage β-cell function is β% = (20 × FPI)/(FPG – 3.5), where FPI is fasting plasma insulin concentration (mU/L) and FPG is fasting plasma glucose (mmol/L). Strong correlations have been demonstrated among the HOMA, the hyperinsulinemic-euglycemic clamp (R2 = .82.88; Bonora et al., 2000; Matthews et al., 1985), and the minimal model assessment (r = .7; Garcia-Estevez, Araujo-Vilar, Fiestras-Janiero, Saavedra-Gonzalez, & Cabezas-Cerrato, 2003). The HOMA has been shown to be sensitive to change and able to detect insulin sensitivity longitudinally (Wallace, Levy, & Matthews, 2004).


Robinson et al. / Exercise in HIV 181 Table 3.

Sample Demographics and HIV Disease-Related Characteristics Completers (n = 5)

Variable Gender Male Female Age (years) Race African American Caucasian HIV risk factors MSM Heterosexual IDU Current or past smoker Duration of HIV infection (years) CD4+ cell number (cells/mm3) Viral load Undetectable Detectable HAART regimen NRTI, PI NRTI, NNRTI NRTI, NNRTI, PI

Noncompleters (n = 4)

4 1 44 ± 3.8

4 0 40.5 ± 7.1

2 3

1 3

4 1 0 2 6.4 ± 2.7 505 ± 296.5

3 0 1 2 11 ± 3.8 538 ± 380.6

3 2a

2 2b

3 2 0

2 1 1

NOTE: Data are mean ± standard deviation for continuous variables and frequencies for categorical variables. MSM = men who have sex with men; IDU = injecting drug user; HAART = highly active antiretroviral therapy; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; NNRTI = nonnucleoside reverse transcriptase inhibitor. a. Actual values were 60 and 1,500 cells/mm3. b. Actual values were 55 and 1,000 cells/mm3.

Results A total of 9 participants were recruited; however, only 5 completed the 16-week intervention and had preintervention and postintervention data available for analysis. Demographic and HIV disease-related characteristics for all recruited participants are shown in Table 3. The mean number of exercise sessions attended by participants who completed the intervention was 43 ± 3.7. All participants were able to exercise at the prescribed duration and intensity without difficulty. Participants who completed the intervention had significantly higher baseline total cholesterol than those who did not complete it (242.8 ± 54.3 vs. 178.8 ± 39.4 mg/dL, respectively). Completers and noncompleters did not significantly differ on other baseline measurements (data not shown). Of those who did not complete the intervention, 2 were lost to follow-up, 1 could not continue because of peripheral neuropathy, and 1 found the time commitment too burdensome. Mean improvement in aerobic capacity (VO2max) was 3.4 ± 3.2 ml/kg/min (from 31.1 ± 5.9 to 34.5 ± 6.8 ml/kg/min; z = –1.75, p = .08), and mean increase in strength was 227.6 ± 84.8 lb, which represents a mean sum of increases in 1-RM for all seven resistance

exercises (from 1,254 ± 341.8 to 1,482.5 ± 299.3 lb; z = –2.02, p = .04). Mean and percentage changes from preintervention to postintervention in outcome measures along with results from paired Wilcoxon rank sum tests are found in Table 4.

Discussion Participants entered the study in an aerobically deconditioned state that improved with training, as evidenced by the increase in aerobic capacity. Strength was significantly improved over the course of the 16week intervention, as shown by the mean sum increase in 1-RM. The only statistically significant outcome measure changes were a decrease in total body and trunk fat as measured by DXA. These two variables are highly correlated, and the loss of trunk fat likely accounts for the significance in loss of total fat. Given the pilot status of these data, the small sample size, and lack of control, definitive conclusions cannot be drawn. However, some intriguing trends were noted that support further testing of exercise in this patient population. In addition, particular methodological issues emerged that can and should be addressed in future testing.


182 BIOLOGICAL RESEARCH FOR NURSING Vol. 8, No. 3, January 2007 Table 4.

Outcome Measures

Variable Visceral fat area (%)a Subcutaneous fat area (%)a Total fat (g)b Total lean tissue (g)b Trunk fat (g)b Trunk lean tissue (g)b Limb fat (g)c Limb lean (g)c Total cholesterol (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol Triglyceride level (mg/dL) β-cell function (%)d Insulin sensitivity (%)d

Prevalue

Postvalue

Absolute Change in Mean

Percentage Change

Wilcoxon Signed Ranks z Scores

9.5 ± 1.7 40.5 ± 6.3 18,895.2 ± 4,467.8 55,068.3 ± 7,676.35 11,446 ± 2,457 11,446 ± 2,457 7,382.5 ± 1,324.7 23,826.1 ± 3,219.5 242.8 ± 54.3 154 ± 39.4 45.6 ± 10.5 221.6 ± 116.5 143.9 ± 95.5 102.1 ± 56.2

8.7 ± 1.5 31.9 ± 7.9 17,570.2 ± 4,369.3 56,384.2 ± 9,331.14 10,454.2 ± 2,508.2 10,454.2 ± 2,508.2 7,036.3 ± 1,561.7 24,286.4 ± 3,893.7 223.4 ± 20.7 140.6 ± 15.1 49.6 ± 10.2 162.6 ± 62.5 107.8 ± 39.7 86.4 ± 27.4

–0.8 ± 0.2 –8.6 ± 10.5 –1,324.9 ± 733.6 1,989.5 ± 1,315.9 –992.8 ± 764.9 973.41 ± 1,226.1 –346.2 ± 301.4 460.3 ± 832.5 –19.4 ± 36.3 –13.4 ± 27.1 4 ± 6.3 –59 ± 69.9 –36.1 ± 114.1 –15.7 ± 41.7

–8.2 –21.2 –7 3.6 –8.7 8.5 –4.7 1.9 –8 –8.7 8.8 –26.6 –25 –15.4

–1.75 –0.94 –2.02* –1.21 –2.02* –1.48 –1.83 –0.73 –0.94 –1.21 –1.22 –1.48 –0.67 –0.67

NOTE: N = 5. Data are mean ± standard deviation. LDL = low-density lipoprotein; HDL = high-density lipoprotein. a. Measured via electron beam tomography; values reported are percentage of adipose tissue area (cm2 of total area of the slice). b. Measured via dual-energy X-ray absorptiometry. c. Measured via dual-energy X-ray absorptiometry; values reported are sums of all four limbs. d. Measured via computer homeostatic model assessment; values reported are percentage function or sensitivity. *p < .05.

The significant loss of trunk fat accompanied by the trend for increased total and limb lean tissue suggests that exercise training may be effective in reducing abdominal adiposity and increasing muscle mass, which may impart greater whole-body insulin sensitivity (Buemann & Tremblay, 1996; Simoneau, Colberg, Thaete, & Kelley, 1995). Previous pilot work of combined endurance and resistance training produced a similar decrease in trunk fat (Roubenoff, Weiss, et al., 1999). The current data failed to support an effect of exercise on the distribution of fat in the abdominal depots. No changes were noted in the area of visceral fat; however, a small but nonsignificant decrease was found for the subcutaneous fat area. The single previous published study that examined changes in abdominal visceral and subcutaneous fat area (measured with computed tomography [CT] scan) as a result of combined endurance and resistance training in an HIV sample showed significantly decreased visceral fat area without changes in the area of subcutaneous fat (Thoni et al., 2002). In repeated-measures design, precise scanning position is critical to ensuring accuracy of the comparisons across time points. Although we used the L4-L5 vertebrae as our landmark for scanning, the radically different within-subject slice circumferences suggest that greater precision in scanning protocol was warranted. Therefore, we chose to report

the percentage of fat relative to the entire area of the slice as a means to standardize across time points. As such, our results should be interpreted cautiously. The mean baseline values were elevated for total and LDL cholesterol and triglycerides. Although not statistically significant, a 59 mg/dL drop in triglyceride level may be clinically significant. Decreases in triglycerides have been shown to occur in previous small studies of resistance (Yarasheski et al., 2001), endurance (Thoni et al., 2002), and combination (Jones et al., 2001) exercise in HIV samples. A small, nonsignificant decrease was noted in total and LDL cholesterol. Previous research testing endurance training with and without a resistance-training component reported significant reductions in total cholesterol, LDL cholesterol, or both (Jones et al., 2001; Thoni et al., 2002). In terms of insulin sensitivity, on average, the sample had normal percentage sensitivity and β-cell function at baseline. Therefore, it would not be expected that insulin sensitivity would improve with exercise. However, the mean percentage sensitivity and β-cell function actually decreased with exercise, although not significantly. Only 1 participant had percentage insulin sensitivity and β-cell values that indicated some level of insulin resistance. This individual responded in the anticipated direction and achieved normal percentage sensitivity and β-cell function


Robinson et al. / Exercise in HIV 183

postintervention. The only other study (Thoni et al., 2002) to assess changes in insulin sensitivity with exercise in an HIV sample (also a small pilot of 9 participants) using a HOMA model likewise found no significant changes. Abundant evidence suggests that the independent effects of exercise (i.e., without concomitant weight loss) are related to the last bout of exercise. Therefore, standardized timing of insulin and glucose levels relative to the last bout of exercise is critical for interpretation of results. Levels of glucose and insulin were drawn within a week of the last exercise session. This timing schema was not precise enough to ensure accurate assessment of changes in insulin sensitivity. In relation to participant recruitment, the current data were based on a relatively homogeneous sample that did not accurately reflect current and emerging U.S. epidemiology. In particular, recruitment of a higher proportion of female participants (particularly minorities) will not only allow for greater generalizability but may also highlight potential gender differences in response to exercise. In addition, similar to the majority of laboratory-based exercise studies, retention of participants proved to be a significant problem. Future testing should include a component to promote adherence to the protocol. For example, social support has been shown to enhance adherence to HAART (Berg et al., 2004; Catz, Kelly, Bogart, Benotsch, & McAuliffe, 2000; van Servellen & Lombardi, 2005). It is therefore likely that an exercise intervention conducted in a group format (perhaps peer led) may promote successful protocol adherence. In conclusion, to date, the effect of endurance and resistance exercise on HIV metabolic abnormalities has been studied in mostly small, uncontrolled studies, including this pilot study. Larger randomized trials, such as the one conducted by Smith and colleagues (2001), used manual anthropomorphic measures to show loss of central fat; it is therefore difficult to compare results to studies using DXA or CT (or magnetic resonance imaging) adipose measurement. A series of reports from Driscoll and colleagues (Driscoll, Meininger, Lareau, et al., 2004; Driscoll, Meininger, Ljungquist, et al., 2004) suggests that resistance exercise and combination endurance/ resistance exercise along with metformin is more effective at enhancing insulin sensitivity than metformin alone in HAART-treated individuals with hyperinsulinemia and fat redistribution. Although informative, these data do not address the role that

exercise may play in preventing the need for pharmacological intervention. No fully powered randomized controlled trial of exercise versus usual activity has been conducted in the post-HAART era that examines lipids, insulin sensitivity, or radiographically measured abdominal adiposity. Such studies are urgently needed, as the current piecemeal evidence is insufficient to provide recommendations. We suggest that investigators conducting future clinical trials of exercise in HIV consider the following. Participants need to be well classified in terms of lipid levels, insulin sensitivity, and fat redistribution at study entry. Given the diversity of expression of metabolic abnormalities in the HIV population, it is unlikely that the full constellation of abnormalities will be found in all participants. Therefore, specific inclusion/exclusion criteria related to the variable of interest or exclusion from analysis of participants with normal baseline values for the variable of interest may be warranted to avoid a statistical floor/ceiling effect. Ideally, randomized trials should contain various dose-response arms with various frequencies, intensities, and durations of endurance or resistance exercise or both. Previously tested frequencies, intensities, and durations are based on data from other populations and may or may not be appropriate in the context of HIV disease. Finally, timing of outcome measures is crucial. Given the acute metabolic effects of exercise on metabolic parameters, it may be prudent to measure lipid levels and insulin sensitivity precisely at 12 to 15 hr after the last bout of exercise and again 72 hr later. Data from both time points may be informative and will provide information related to acute exercise effects as well as sustained effects that might occur because of such phenomena as muscle hypertrophy.

References American College of Sports Medicine, & Roitman, J. L. (2001). ACSM’s resource manual for guidelines for exercise testing and prescription (4th ed.). Baltimore: Lippincott Williams & Wilkins. Berg, K. M., Demas, P. A., Howard, A. A., Schoenbaum, E. E., Gourevitch, M. N., & Arnsten, J. H. (2004). Gender differences in factors associated with adherence to antiretroviral therapy. Journal of General Internal Medicine, 19, 1111-1117. Blake, G. L., Wahner, H. W., & Fogelman, I. (1999). The evaluation of osteoporosis: Dual energy X-ray absorptiometry and ultrasound in clinical practise. London: Martin Dunitz. Bonora, E., Targher, G., Alberiche, M., Bonadonna, R. C., Saggiani, F., Zenere, M. B., et al. (2000). Homeostasis model


184 BIOLOGICAL RESEARCH FOR NURSING Vol. 8, No. 3, January 2007 assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care, 23, 57-63. Borkan, G. A., Gerzof, S. G., Robbins, A. H., Hults, D. E., Silbert, C. K., & Silbert, J. E. (1982). Assessment of abdominal fat content by computed tomography. American Journal of Clinical Nutrition, 36, 172-177. Bozzette, S. A., Ake, C. F., Tam, H. K., Chang, S. W., & Louis, T. A. (2003). Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection. New England Journal of Medicine, 348, 702-710. Buemann, B., & Tremblay, A. (1996). Effects of exercise training on abdominal obesity and related metabolic complications. Sports Medicine, 21, 191-212. Carpinelli, R. N., & Otto, R. M. (1998). Strength training: Single versus multiple sets. Sports Medicine, 26, 73-84. Catz, S. L., Kelly, J. A., Bogart, L. M., Benotsch, E. G., & McAuliffe, T. L. (2000). Patterns, correlates, and barriers to medication adherence among persons prescribed new treatments for HIV disease. Health Psychology, 19, 124-133. DeNino, W. F., Tchernof, A., Dionne, I. J., Toth, M. J., Ades, P. A., Sites, C. K., et al. (2001). Contribution of abdominal adiposity to age-related differences in insulin sensitivity and plasma lipids in healthy nonobese women. Diabetes Care, 24, 925-932. Driscoll, S. D., Meininger, G. E., Lareau, M. T., Dolan, S. E., Killilea, K. M., Hadigan, C. M., et al. (2004). Effects of exercise training and metformin on body composition and cardiovascular indices in HIV-infected patients. AIDS, 18, 465-473. Driscoll, S. D., Meininger, G. E., Ljungquist, K., Hadigan, C., Torriani, M., Klibanski, A., et al. (2004). Differential effects of metformin and exercise on muscle adiposity and metabolic indices in human immunodeficiency virus-infected patients. Journal of Clinical Endocrinology & Metabolism, 89, 2171-2178. Durstine, J. L., Grandjean, P. W., Davis, P. G., Ferguson, M. A., Alderson, N. L., & DuBose, K. D. (2001). Blood lipid and lipoprotein adaptations to exercise: A quantitative analysis. Sports Medicine, 31, 1033-1062. El-Sadr, W. M., Mullin, C. M., Carr, A., Gibert, C., Rappoport, C., Visnegarwala, F., et al. (2005). Effects of HIV disease on lipid, glucose and insulin levels: Results from a large antiretroviral-naive cohort. HIV Medicine, 6, 114-121. Franklin, B. A. (Ed.). (2000). ACSM’s guidelines for exercise testing and prescription (6th ed.). Philadelphia: Lippincott Williams & Wilkins. Garcia-Estevez, D. A., Araujo-Vilar, D., Fiestras-Janeiro, G., Saavedra-Gonzalez, A., & Cabezas-Cerrato, J. (2003). Comparison of several insulin sensitivity indices derived from basal plasma insulin and glucose levels with minimal model indices. Hormone & Metabolic Research, 35, 13-17. Grinspoon, S., & Carr, A. (2005). Cardiovascular risk and bodyfat abnormalities in HIV-infected adults. New England Journal of Medicine, 352, 48-62. Grinspoon, S. K. (2005). Metabolic syndrome and cardiovascular disease in patients with human immunodeficiency virus. American Journal of Medicine, 118(Suppl. 2), 23S-28S. Hadigan, C., Corcoran, C., Basgoz, N., Davis, B., Sax, P., & Grinspoon, S. (2000). Metformin in the treatment of HIV

lipodystrophy syndrome: A randomized controlled trial. Journal of the American Medical Association, 284, 472-477. Hadigan, C., Meigs, J. B., Corcoran, C., Rietschel, P., Piecuch, S., Basgoz, N., et al. (2001). Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clinical Infectious Diseases, 32, 130-139. Ivy, J. L. (1997). Role of exercise training in the prevention and treatment of insulin resistance and non-insulin-dependent diabetes mellitus. Sports Medicine, 24, 321-336. Jones, S. P., Doran, D. A., Leatt, P. B., Maher, B., & Pirmohamed, M. (2001). Short-term exercise training improves body composition and hyperlipidaemia in HIV-positive individuals with lipodystrophy. AIDS, 15, 2049-2051. Kvist, H., Chowdhury, B., Grangard, U., Tylen, U., & Sjostrom, L. (1988). Total and visceral adipose-tissue volumes derived from measurements with computed tomography in adult men and women: Predictive equations. American Journal of Clinical Nutrition, 48, 1351-1361. Lichtenstein, K. A., Ward, D. J., Moorman, A. C., Delaney, K. M., Young, B., Palella, F. J., Jr., et al. (2001). Clinical assessment of HIV-associated lipodystrophy in an ambulatory population. AIDS, 15, 1389-1398. Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985). Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 28, 412-419. Palella, F. J., Baker, R., Moorman, A. C., Chmiel, J. S., Wood, K. C., & Holmberg, S. D. (2004, February). Mortality and morbidity in the HAART era: Changing causes of death and disease in the HIV outpatient study. Paper presented at the 11th Conference on Retroviruses and Opportunistic Infections, San Francisco. Palella, F. J., Delaney, K. M., Moorman, A. C., Loveless, M. O., Fuhrer, J., Satten, G. A., et al. (1998). Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. New England Journal of Medicine, 338, 853-860. Poehlman, E. T., Dvorak, R. V., DeNino, W. F., Brochu, M., & Ades, P. A. (2000). Effects of resistance training and endurance training on insulin sensitivity in nonobese, young women: A controlled randomized trial. Journal of Clinical Endocrinology & Metabolism, 85, 2463-2468. Pritchard, J. E., Nowson, C. A., Strauss, B. J., Carlson, J. S., Kaymakci, B., & Wark, J. D. (1993). Evaluation of dual energy X-ray absorptiometry as a method of measurement of body fat. European Journal of Clinical Nutrition, 47, 216-228. Riddler, S. A., Smit, E., Cole, S. R., Li, R., Chmiel, J. S., Dobs, A., et al. (2003). Impact of HIV infection and HAART on serum lipids in men. Journal of the American Medical Association, 289, 2978-2982. Robinson, F. P. (2004). HIV lipodystrophy syndrome: A primer. Journal of the Association of Nurses in AIDS Care, 15, 15-29. Ross, R., Freeman, J. A., & Janssen, I. (2000). Exercise alone is an effective strategy for reducing obesity and related comorbidities. Exercise & Sport Sciences Reviews, 28, 165-170. Roubenoff, R., McDermott, A., Weiss, L., Suri, J., Wood, M., Bloch, R., et al. (1999). Short-term progressive resistance training increases strength and lean body mass in adults


Robinson et al. / Exercise in HIV 185 infected with human immunodeficiency virus. AIDS, 13, 231-239. Roubenoff, R., Weiss, L., McDermott, A., Heflin, T., Cloutier, G. J., Wood, M., et al. (1999). A pilot study of exercise training to reduce trunk fat in adults with HIV-associated fat redistribution. AIDS, 13, 1373-1375. Shlay, J. C., Visnegarwala, F., Bartsch, G., Wang, J., Peng, G., El-Sadr, W. M., et al. (2005). Body composition and metabolic changes in antiretroviral-naive patients randomized to didanosine and stavudine vs. abacavir and lamivudine. Journal of Acquired Immune Deficiency Syndromes, 38, 147-155. Simoneau, J. A., Colberg, S. R., Thaete, F. L., & Kelley, D. E. (1995). Skeletal muscle glycolytic and oxidative enzyme capacities are determinants of insulin sensitivity and muscle composition in obese women. FASEB Journal, 9, 273-278. Smith, B. A., Neidig, J. L., Nickel, J. T., Mitchell, G. L., Para, M. F., & Fass, R. J. (2001). Aerobic exercise: Effects on parameters related to fatigue, dyspnea, weight and body composition in HIV-infected adults. AIDS, 15, 693-701. Thaete, F. L., Colberg, S. R., Burke, T., & Kelley, D. E. (1995). Reproducibility of computed tomography measurement of visceral adipose tissue area. International Journal of Obesity & Related Metabolic Disorders, 19, 464-467. Thoni, G. J., Fedou, C., Brun, J. F., Fabre, J., Renard, E., Reynes, J., et al. (2002). Reduction of fat accumulation and lipid disorders by individualized light aerobic training in human

immunodeficiency virus infected patients with lipodystrophy and/or dyslipidemia. Diabetes & Metabolism, 28, 397-404. van Servellen, G., & Lombardi, E. (2005). Supportive relationships and medication adherence in HIV-infected, low-income Latinos. Western Journal of Nursing Research, 27, 1023-1039. Visnegarwala, F., Maldonado, M., Sajja, P., Minihan, J. L., Rodriguez-Barradas, M. C., Ong, O., et al. (2004). Lipid lowering effects of statins and fibrates in the management of HIV dyslipidemias associated with antiretroviral therapy in HIV clinical practice. Journal of Infection, 49, 283-290. Wallace, T. M., Levy, J. C., & Matthews, D. R. (2004). Use and abuse of HOMA modeling. Diabetes Care, 27, 1487-1495. Wang, Z. M., Visser, M., Ma, R., Baumgartner, R. N., Kotler, D., Gallagher, D., et al. (1996). Skeletal muscle mass: Evaluation of neutron activation and dual-energy X-ray absorptiometry methods. Journal of Applied Physiology, 80, 824-831. Wellens, R., Chumlea, W. C., Guo, S., Roche, A. F., Reo, N. V., & Siervogel, R. M. (1994). Body composition in white adults by dual-energy X-ray absorptiometry, densitometry, and total body water. American Journal of Clinical Nutrition, 59, 547-555. Yarasheski, K. E., Tebas, P., Stanerson, B., Claxton, S., Marin, D., Bae, K., et al. (2001). Resistance exercise training reduces hypertriglyceridemia in HIV-infected men treated with antiviral therapy. Journal of Applied Physiology, 90, 133-138.
