EAL

H/A: Physical Activity (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine the effects of human immunodeficiency virus (HIV) and highly active anti-retroviral therapy (HAART) on oxygen on-kinetics in HIV-positive persons.

Inclusion Criteria:

Asymptomatic HIV infection (US Centers of Disease Control and Prevention stages A1 or A2)
Sedentary lifestyle: Defined as not having participated in an exercise program during the past six months or routinely engaged in employment or other activity that would cause perspiration on the average of once a week.

Exclusion Criteria:

Diagnosis of acquired immune deficiency syndrome (AIDS), defined as currently having or having a history of an opportunistic infection or a CD4 count below 200.

Description of Study Protocol:

Recruitment

Recruited from an infectious disease clinic by their physician or nurse practitioner and evaluated for inclusion in the study
Non-infected sedentary controls were recruited from a convenience sample from the surrounding community.

Design

Case-control study

Blinding used (if applicable)

Assumed for lab measures

Intervention (if applicable)

Comparison groups were

Infected with HIV taking HAART (HIV+/Med+)
Infected with HIV not taking HAART (HIV+/Med-)
Non-infected controls.

Statistical Analysis

Pearson product-moment correlation coefficients were calculated to identify significant relationships among group and subject descriptive data and dependent variables
Descriptive data were then assessed for intergroup differences by using analyses of variance (ANOVAs) and demographic variables
Three-way ANOVAs were used to determine the main effect influences of group (HIV on HAART, HIV not on HAART, controls), gender (female, male) and race (African American, Caucasian) and their interactions on oxygen on-kinetics and cardiorespiratory response
Separate ANOVAs were used for the 3.0 METS (fixed work) and 70% peak VO₂ (variable work, relative work) analyses
Tukey post-hoc analyses of individual treatment means with certainty set at an alpha of 0.05 and least square means and post-hoc analyses followed the finding of a significant F ratio in analyses when the number of comparisons was greater than two
Statistical and biologic plausibility for confounding covariance was determined as a result of variability associated with power output (watts).

Data Collection Summary:

Timing of Measurements

One-time measurement

Dependent Variables

Trackster treadmill with a microprocessor interface was used for both sub-maximal and maximal exercise tests
VO₂ and oxygen on-kinetic measurements were made by using a Medgraphics CPX/D metabolic cart
Oxygen on-kinetics: MRT, delta VO₂, oxygen deficit, sum of VO₂, ORI
- Calculated by MedGraphics Breeze software for both sub-maximal tests
- MRT: Mean response time, a reported index of the rate at which the steady-state or asymptotic phase can be attained is calculated as a time constant from a monoexponential fit of VO₂ from baseline VO₂ to its asymptotic phase of the oxygen on-kinetics curve. Takes into account both the phase I and phase II time constants and represents a mean fit of both. At six minutes of exercise and calculated as 63% of the phase II VO₂ time curve, or the total time from rest or previous workload minus 20 seconds (phase I) times 0.63.
- Delta VO₂: Change in VO₂ from baseline to the asymptotic phase of the oxygen-time curve III, represents the ability of the oxidative system to increase VO₂ to meet the energy demands of a particular workload. Change in VO₂ from baseline value at time zero (either rest or previous exercise intensity) and VO₂ at six minutes.
- Oxygen deficit: Determined by the equation (t x change VO₂) - sum of VO₂; t=time from rest of previous workload to steady state
- Sum of VO₂: Calculated as the integral of the VO₂ time curve, which approximates the sum of consumed oxygen from rest to exercise cessation at six minutes
- ORI: Oxidative response index-the combined ratio of delta VO₂ and MRT may reveal the physiologic capacity to consume oxygen per unit of time from baseline to the onset of phase III on the oxygen on-kinetics curve and may serve as index of the responsiveness of the oxidative metabolic system.
Cardiorespiratory response: VO₂, cardiac output, Vs, heart rate, a-VO₂
- Cardiac output: Determined by the indirect Fick method using the equations described by Jones (1997)
- V_s: Cardiac stroke volume was determined as the ratio of cardiac output and heart rate
BSA: Body surface area was determined by the equation: 0.20247 x height (m)⁰^.725 x weight (kg)^0.425
BMI: Body mass index was determined by the equation: Weight (kg)/height (m)²
Lactate: Arterialized fingerstick lactate sampling and analysis.

Independent Variables

Infected with HIV taking HAART (HIV+/Med+)
Infected with HIV not taking HAART (HIV+/Med-)
Non-infected controls.

Control Variables

Race and gender

Description of Actual Data Sample:

Initial N

39 (13 per comparison group; eight men and five women per group)

Attrition (final N)

Age

Means ranged from 32.8 to 36.1 years

Ethnicity

Not stated

Other relevant demographics

Anthropometrics

BMI (kg/m²): HIV+/Med+ 26.3±1.2; HIV+/Med- 25.8±1.6; Control 25.0±0.6
BSA: HIV+/Med+ 2.0±0.11; HIV+/Med- 1.9±0.06; Control 2.0±0.6
No significant differences among the groups in age, height, weight, BMI or BSA.

Location

Participants infected with HIV were recruited from an infectious disease clinic. Non-infected sedentary controls were recruited from a convenience sample from the surrounding community.

Summary of Results:

Table 2. Serologic characteristics of groups with HIV

	HIV+/MEd+	HIV+/Med-
CD4 (cells/mm3)	476.9±70.5	397.2±48.6
Leukocyte (x10³ uL)	5.2±1.1	5.0±0.4
Viral Load (copies/cm³)	2,511.3±2,121.1	79,353.3±32,159.9^*
Hematocrit (percentage)	39.8±1.1	39.6±1.1
Hemoglobin (mmol/L)	13.6±0.4	13.3±0.4
Duration of HIV (mo)	89.0±16.5	60.0±20.9

Values are mean ± SE. ^*P<0.02.

Table 4. Route of Infection in Groups with HIV

	HIV+/MEd+	HIV+/Med-	Excluded
IVDA	2	5	19
MSM	4	2	7
Heterosexual	7	5	13
Unknown	0	1	9

Abbreviations: IVDS, intravenous drug abuse; MSM, men sex with men; heterosexual, heterosexual contact.

Table 5. Relationships (r) among oxygen on-kinetic and cardiorespiratory variables at six minutes of exercise.

			Oxygen On-Kinetic Values
Cardiorespiratory value	MRT	O₂ Deficit	Change VO₂	SumVO₂	ORI
VO₂	0.47	0.80	0.86	0.71	0.46
Cardiac output	0.41	0.69	0.87	0.62	0.35
Vs	NS	NS	NS	NS	NS
a-VO₂	0.32	0.58	0.62	0.44	0.33
Heart rate	0.49	0.56	0.82	0.50	NS

Note: All values are significant at P<0.001. Abbreviations: NS, not significant.

Table 6. Cardiorespiratory variables at Peak Exercise

	HIV+/Med+	HIV+Med-	Controls
VO₂ (mL/min)	2,063.1±122.0^*	2,127.2±182.1	2,676.7±205.1
VO₂ (mL/min^-1)	26.4±1.6^*	28.6±2.6	34.5±2.2
Cardiac output (L/min)	20.9±1.2	18.0±1.3	20.7±1.4
Vs (mL/beat)	123.7±7.8	99.8±6.6	112.5±7.3
a-VO₂ (vol percentage)	9.9±0.7^*	11.8±0.5	13.0±0.6
RER	1.25±0.03	1.21±0.03	1.32±0.03
Heart rate (bpm)	170.9±4.9^*	179.8±3.4	183.5±2.7
V_T (mL/kg^-1/min^-1)	14.6±0.9	16.2±1.1	16.7±0.8
Lactate (mmol/dL)	6.9±1.1^*	7.5±1.1^*	11.3±0.9

Note: Values are mean ± SE (ANOVA). ^*Significantly different from controls.

Table 10. Oxygen On-Kinetic Variables (above ventilatory threshold)

	HIV+/Med+	HIV+/Med-	Controls
MRT (s)	65.0±3.8	57.2±4.5	63.3±4.2
O₂ deficit (mL)	1,039.2±108.0	901.2±169.5^*	1,378.0±154.2
Change VO₂ (mL)	946.5±68.1^*	871.6±119.6^*	1,265.3±99.8
Sum VO₂ (mL)	2,566.4±381.3^*	2,128.6±510.6^*	4,173.1±510.9
ORI (mL/s)	15.0±1.3^*	15.1±1.7^*	20.8±2.1

^*Significantly different (P<0.05) from controls.

Other Findings

Medication regimen for group with HIV taking HAART: Stavudine (N=5); Didanosine (N=2); Zidovudine (N=7); Lamivudine (N=6); Protease inhibitors (N=4); Non-nucleoside reverse transcriptase inhibitors (N=5); Mean duration of HAART ± SE (mo) 38.3±6.3
All participants stopped exercise because of volitional exhaustion and not for any other reason
Peak power output (with maximal exercise) was higher (P<0.01) in controls (292.5±22.8W) compared with participants with HIV taking HAART (233.5±16.1W) and those not taking HAART (239.1±21.3W)
Peak power output (with sub-maximal exercise) was not different among groups.

Author Conclusion:

Our study found impaired oxygen on-kinetics during sub-maximal exercise above the ventilatory threshold, in participants with HIV compared with a non-HIV-infected control group matched for age, gender and activity level
It appears that HIV infection and not HAART, mediated the impaired oxygen on-kinetics in these individuals
This finding differs from another investigation, which determined that muscle oxygen extraction utilization was diminished by the use of HAART and not HIV infection (Cade et al, 2003). Reasons for this difference remain unknown.

Funding Source:

Other:

unknown

Reviewer Comments:

Funding source not identified
Limitations as stated by the authors:
- Relatively small sample size (N=39)
- Moderate coefficients of variation
- Design of the study; design was used secondary to practical limitations and was meant to describe the relationship between HIV, HAART and oxygen kinetics.

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?		???
	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?		???
	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?	No
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	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.)	???
	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%.)	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?	No
	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.)	???
	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?	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?	Yes
	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?	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