EAL

H/A: Physical Activity (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine the nature and severity of impaired physical functioning in older HIV-infected adults on HAART using standard gerontological measures of physical activity and exercise treadmill testing
To investigate the association of age and reduced aerobic capacity in this patient population.

Inclusion Criteria:

HIV-infected male veterans aged 40 to 69 years. Subjects had to be free of any AIDS-defining illness for six months prior to enrollment to minimize confounding by effects of opportunistic infections
Healthy male controls were sedentary men aged 51 to 79 years who had been enrolled in previous longitudinal exercise studies
Smokers were included since 70% of clinic patients were active smokers.

Exclusion Criteria:

Comorbid conditions that would prevent the subject from safely undergoing treadmill exercise testing, such as angina, severe anemia (hematocrit less than 25%), symptomatic peripheral arterial disease, renal failure, cirrhosis, poorly controlled hypertension (blood pressure systolic more than 180mm Hg and diastolic more than 95mm Hg) and congestive heart failure
Patients who were actively training aerobically
Healthy controls had no history of coronary artery disease, stroke, diabetes and end-stage renal, liver and pulmonary disease studied at the 1996 longitudinal follow-up visit.

Description of Study Protocol:

Recruitment

HIV-infected men 40 years and older were recruited from the HIV Clinic at the Baltimore VA Medical Center. Healthy controls were 167 nonsmoking men enrolled into longitudinal exercise studies between 1985 and 1993.

Design

Case-control study.

Intervention

Functional performance testing including treadmill testing was completed in HIV-infected male veterans and controls.

Statistical Analysis

To evaluate the association of age with functional performance, HIV-infected subjects were classified as younger (40 to 49 years, N=12) or older age (50+ years, N=20)
Student's T-test or Mann-Whitney U test and chi-squared test or Fischer's exact test were used to assess differences in patient characteristics between age groups for continuous and categorical variables
To test the association of physical functioning with age and clinical factors, Student's T-test or ANOVA was used with different outcome measures
Linear regression was used to assess differences in aerobic capacity for patient characteristics using peak aerobic capacity as the outcome
Characteristics that were statistically significant were included in the multivariate analysis
To investigate the loss of peak aerobic capacity with age in HIV-infected vs. healthy subjects, the difference in the Pearson's correlation coefficient for each group was tested usign Fischer's R-to-Z transformation.

Data Collection Summary:

Timing of Measurements

All subjects received a baseline history and physical and electrocardiogram (EKG).

Dependent Variables

Functional performance testing included measures of strength, activities of daily living and cardiorespiratory fitness
Grip strength measured with Lafayette hand dynamometer
Six-minute walk distance
Graded exercise testing on a motorized treadmill while open circuit spirometry measured oxygen consumption, carbon dioxide production and minute ventilation.

Independent Variables

HIV infection
Age.

Control Variables

Information on physical activity, smoking history, past medical history, ADI and HAART history obtained through questionnaires, subject self-report and review of the patients' electronic medical record.

Description of Actual Data Sample:

Initial N: 32 HIV-infected male veterans, 47 healthy male controls
Attrition (final N): As above. 12 were aged 40 to 49 years, 20 were aged over 50 years.
Age: Veterans aged 40 to 69 years
Ethnicity: HIV-infected male veterans (90.6% African American, 9.4% white)

Other Relevant Demographics

Mean CD4 count: 347 (range 18 to 1,401) cells per ml
Mean viral load: 11,609±32,749 copies per ml
Mean BMI: 24.3±4.6
88% were currently on HAART.

Anthropometrics

Cumulative HAART exposure by drug class was not different between the age groups. Mean hematocrit and serum albumin were lower in the older age group.

Location

Baltimore, Maryland.

Summary of Results:

Factor	Total (N=32)	Aged 40 to 49 Years (N=12)	Aged > 50 Years (N=20)	P-value
Six-minute walk distance (m)	539.0±81.6	558.1±84.8	527.6±79.6	0.3
Grip strength (kg)	41.6±7.3	46.2±6.6	38.8±6.4	<0.01
Peak aerobic capacity (L per minute)	1.6±0.5	1.9±0.4	1.4±0.5	0.01
Peak aerobic capacity (ml per kg per minute)	21.4±5.9	25.2±4.2	19.1±5.7	<0.01
Reduced peak aerobic capacity (percent)	41.1±15.3	35.5±10.5	44.6±16.8	0.1
Predicted maximum heart rate (percent)	83.6±11.0	86.0±11.3	82.2±10.9	0.3

Other Findings

Peak aerobic capacity was significantly reduced in the older vs. younger HIV subjects (19.1±5.7 ml per kg per minute vs. 25.2±4.2, P<0.01).

Peak aerobic capacity was reduced 41%±15% in HIV-infected subjects compared to expected values from age-matched healthy controls (21.4±5.9 ml per kg per minute vs. 36.2±2.8, P<0.01).

Regression analyses show a similar decline in peak aerobic capacity with age in HIV-infected and healthy controls.

Mean six-minute walk distance was not significantly different between the HIV-infected age groups, and was reduced only 8% compared to expected values for healthy adults.

Current CD4 count and HAART exposure were similar in the two age groups and were not significantly associated with peak aerobic capacity.

Anemia (HCT less than 35%) was significantly associated with reduced peak aerobic capacity (P=0.02) but this association was not independent of the effect of age (P=0.1).

Author Conclusion:

We conclude that older HIV-infected adults have markedly impaired aerobic capacity but maintain the capacity to undertake day-to-day activities. Additional physiologic and metabolic testing is needed to measure the effect of HAART toxicity and primary aging on aerobic capacity, and to determine if older HIV-infected adults are at greater risk.

Funding Source:

Government:

NIH, NCRR, NIA

University/Hospital:

University of MD GCRC Grant M01 RR 16500

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Subjects were smokers and controls were nonsmokers, and were studied at different times. Authors note the following strengths and limitations:

Strengths:
- First study focusing on the effect of aging on aerobic capacity and functional performance in HIV-infected adults
- Recruited and characterized HIV patients who receive HIV care from VA, complete data available
Limitations:
- HIV-infected men represent a selected group who volunteered for the study and may not be representative of the population of patients with HIV
- Small sample size also limits generalizability
- Difference in non-HIV medical comorbidities between HIV-infected and non-infected controls
- Older HIV subjects may have been infected for a longer period of time than the younger subjects.

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?		No
	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?	???
	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.)	No
	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?	N/A
	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?	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