EAL

H/A: Physical Activity (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine the extent of neuromuscular activation of the knee extensors and ankle dorsiflexors of men infected with HIV receiving antiretroviral therapy and its relationship to muscle performance.

Inclusion Criteria:

HIV-infected males
Subjects had been prescribed HAART for more than six months prior to the start of the study.

Exclusion Criteria:

Any AIDS-defining illness within the previous six months
Anabolic steroid use or growth hormone replacement
Major comorbidities that would preclude functional testing
Patients with the following conditions: Myocardial infarction, unstable angina, uncontrolled hypertension, poorly controlled diabetes mellitus, peripheral vascular disease leading to claudication, end-stage liver disease, renal dialysis, severe anemia, severe pulmonary disease-related disability, other neurological impairments or use of home oxygen.

Description of Study Protocol:

Recruitment

30 community-dwelling patients with HIV were recruited from the Baltimore VA Medical Center HIV Clinic.

Design

Cross-sectional study.

Statistical Analysis

Linear regression analyses were performed to determine the strengths of the relationships among the variables of interest
The subjects were divided into two groups post-hoc, based on the quadriceps femoris central activation ratio data, and comparisons between these two groups were evaluated by unpaired T-tests or Wilcoxon tests for nonparametric data
Chi-square tests were used for frequency count data
Linear regression analyses were used to investigate the relationship between quadriceps torque and central activation ratio and muscle cross-sectional area within the low and high central activation ratio groups
Finally, stepwise regression analyses were used to investigate the amount of quadriceps maximum voluntary isometric contractions torque variability explained by the combination of central activation ratio and muscle cross-sectional area for all subjects as well as the low and normal central activation ratio groups.

Data Collection Summary:

Timing of Measurements

All subjects underwent a comprehensive history and physical examination, including blood sampling and electrocardiogram. Blood sampling was performed on the day of enrollment.

Dependent Variables

Central activation ratio was determined using superimposed electrical stimulation during maximum voluntary contractions
Muscle cross-sectional area and composition was evaluated using computed tomography
Muscle performance testing of the ankle dorsiflexors and knee extensors using dynamometer
Aerobic capacity was determined from treadmill exercise testing
Blood sampling for CD4 cell count, HIV viral load, and a polymerase chain reaction assay for the quantification of HIV type 1
Six-minute walk distance.

Independent Variables

HIV infection.

Description of Actual Data Sample:

Initial N: 30 men
Attrition (final N): 27 men. Two subjects disclosed noncompliance with HAART and one transgender subject were excluded.
Age: 48.7±6.5 years
Ethnicity: 93% were African American.

Other Relevant Demographics

Mean CD4 count: 408±293 cells per mm³
Mean viral load: 2.18±0.94 log copies per ml
All subjects were on a nucleoside reverse transcriptase inhibitor-based regimen with 82% receiving a protease inhibitor as a third agent.

Location

Maryland.

Summary of Results:

Variables	All Subjects (N=27)	Low CAR Group (N=11)	Normal CAR Group (N=16)	Statistical Significance of Group Difference
Age (years)	48.7±6.5	48.1±6.8	49.1±6.4	0.70
Weight (kg)	75.7±14.9	72.8±11.3	77.6±16.9	0.44
Height (m)	1.77±0.08	1.76±0.08	1.78±0.08	0.41
BMI	24.2±4.1	24.1±4.4	24.2±4.0	0.92
Quadriceps femoris muscle attentuation (Hounsfield units)	56.0±5.5	57.0±4.8	55.6±6.0	0.51
VO_2peak(ml per kg per minute)	22.6±5.0	21.4±4.4	23.4±5.4	0.30
Maximum heart rate (beats per minute)	142±20	148±18	134±21	0.09
RER	1.08±0.10	1.02±0.1	1.12±0.08	0.01
Treadmill max work rate (W)	125±46	98±31	143±46	0.01
6MWD (m)	593±73	584±83	599±67	0.61

Other Findings

The principal finding of this study was that nearly half (approximately 40%) of subjects with HIV on HAART had an impaired ability to activate their knee extensor muscles, which was associated with weakness and decreased specific force, although no deficits in the central activation of the dorsiflexor muscles were observed.

11 of the subjects had an impaired ability to activate the knee extensors (central activation ratio, 0.72±0.12) that was associated with weakness and decreased specific force.

The reduced central activation was not associated with muscle area, body composition, aerobic capacity, CD4 count or medication regimen.

Those individuals with low central activation had higher HIV-1 viral loads and were more likely to have a history of AIDS-defining illness.

The inability of the low central activation ratio group to fully activate their knee extensors was unrelated to muscle size or composition or to VO_2peak.

Author Conclusion:

Overall, the results of this study indicate that impaired central activation may be a problem in a significant proportion of individuals with HIV, although perhaps not in all muscle groups. The subjects with impaired central activation were weaker than those without impairment, but their muscles were of similar sizes. Consequently, impaired central activation was associated with reduced specific force, although mechanisms other than the loss of central activation may well have been at work. Contrary to our hypothesis of a link between aerobic capacity and central activation ratio, the two groups did not differ with regard to VO_2peak, although some form of aerobic impairment may have been present in the low central activation ratio group. These subjects attained similar VO_2peak values to the normal central activation ratio group, while performing at lower work rates. In these subjects, the central activation deficit appeared to be more closely linked to viral loads and past history of AIDS-defining illnesses than to HAART medications, suggesting that this impairment is related to the progression of the disease itself. While such a mechanism would be consistent with existing reports of impaired motor function in HIV-positive individuals, further research is needed to examine this possibility.

Funding Source:

Government:	VA Research Career Scientist Award and VA Geriatric Research, Clinical and Education Center, National Center for Rehabilitation Research, National Institutes on Aging
University/Hospital:	University of Maryland Claude D. Pepper Older Americans Independence Center (P60-AG12583) and University of Maryland GCRC (M01 RR 16500)

Reviewer Comments:

Authors note that the present study is limited by a small homogeneous patient sample and less than one year of HAART data.

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?		???
	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)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	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?	???
	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?	N/A
	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?	No
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