EAL

H/A: Body Composition Measurement (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To compare regional body fat distribution using quantitative computed tomography (CT) and metabolic parameters in a cohort of 154 HIV-infected male patients experiencing various fat distribution disorders and treated with different antiretroviral regimens
Also to evaluate the relative effects of antiretroviral drugs, as well as correlations between insulin levels and viral load, CD4 cell count, lipid and endocrine profiles and adipose tissue areas of the patients.

Inclusion Criteria:

Age older than 18 years
Biologically documented HIV-1 infection (positive HIV-antibody test)
Active follow-up or medical management of their disease during the previous 12 months
Male
Informed consent was obtained
Protocol approved by the Institutional Ethics Committee of the University of Lyon.

Exclusion Criteria:

Unrestricted eligibility; if they met inclusion criteria, they were included.

Description of Study Protocol:

Recruitment

Subjects were recruited at five AIDS clinical trial units to be in LIPOCO cohort. (LIPOCO study is a French observational cohort study of risk factors for the development of changes in body fat distribution.)

Design

Baseline data from an observational cohort study was used in this cross-sectional analysis. Information was obtained from patient charts and patient interviews at enrollment. Patients were divided into four pre-determined clinical categories of fat distribution: lipoatrophy, obesity, mixed condition and normal. Body composition (bioelectrical impedance analysis and skinfold thickness), fat distribution (CT) and laboratory parameters (plasma glucose and insulin concentrations fasting and during an oral glucose tolerance test, endocrine profile and lipid profile) were measured and compared among the four groups. Nutritional intake was also assessed from a self-administered questionnaire that patients recorded for three days preceding study entry.

Statistical Analysis

Data was compared between four clinical categories used to classify patients according to their fat distribution clinical characteristics, and also between patients receiving a zidovudine-containing regimen and patients receiving a stavudine-containing regimen
Statistical Analysis System software was used for statistical analysis
Continuous variables were analyzed by analysis of variance methods. Logistic regression was used to establish multivariate models to the assess odds ratio of developing changes in body fat distribution, lipoatrophy and mixed syndromes according to antiretroviral drugs. Pearson product-moment correlation coefficients were used to quantify associations between two variables.

Data Collection Summary:

Timing of Measurements

Observational study: one-time measurement.

Dependent Variables

Antiretroviral treatment: therapy naive, nucleoside reverse transcriptase inhibitor, protease inhibitor
Physical exam to assess fat distribution pattern (to divide into one of four groups as noted above)
Body fat distribution measured with CT
Body composition assessed with bioelectrical impedance and skinfold caliper measurements
Lipid profile: serum total cholester0l and triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 and B, uric acid and free fatty acids
Measurement of gonadal and adrenal function: plasma testosterone, follicle stimulating hormone, luteinizing hormone, cortisol
CD4 cell count and quantitative HIV-1 RNA
Oral glucose tolerance test.

Independent Variable

HIV infection.

Control Variables

Nutrient intake also assessed by participants completing a self-administered questionnaire for three days prior to study entry.

Description of Actual Data Sample:

Initial N: 214 patients in the LIPOCO cohort (154 men, 60 women)

Attrition (final N): 154 men

Mean Age: 40.24 years

Ethnicity: Not stated

Other relevant demographics: 27.92% with AIDS

Anthropometrics: Mean body mass index (BMI)=23; no significant difference in groups in weight or BMI

Location: Five AIDS clinical trial clinics, France.

Summary of Results:

Disease Status and Antiretroviral Treatment Characteristics

	All Groups (n=154)	Therapy-naive Group (n=15)	Nucleoside Reverse Transcriptase Inhibitor (NRTI) Group (n=39)	Protease Inhibitor (PI) Group (n=100)	P-value
Duration of HIV Infection (years)	7.32±0.55	3.47±0.74**	7.15±0.41	7.91±0.62	**P<0.01 NRTI and PI vs. therapy-naive
Duration of Antiretroviral Therapy (months)	46.48+2.56	N/A	28.25+3.04**	54.51±3.39	**P<0.01 PI vs. NRTI
CD4 count (cellx10⁶/L)	429±17.62	367.90±64.02**	543.90±25.56**	394.30±24.09	**P<0.01 PI vs. NRTI and NRTI vs. therapy-naive
HIV RNA (log₁₀)	3.15±0.11	5.08±0.16**	3.04±0.22	2.90±0.13	**P<0.001 PI vs. therapy-naive, NRTI vs. therapy-naive
AIDS (% of patients)	27.92	0.65**	0.00	27.27	**P<0.001 PI vs. therapy-naive
Cholesterol (mmol/L)		4.75±0.37**	4.86±0.13**	5.95±0.17	**P<0.01 PI vs. therapy-naive and PI vs. NRTI
Triglycerides (mmol/L)		1.3±0.15*	1.95±0.23**	3.08±0.27	P<0.005 PI vs. therapy-naive *P<0.001 PI vs. NRTI
Fat Mass (kg)		12.1±1.17*	11.54±1**	9.47±0.63	P<0.05 PI vs. therapy-naive *P<0.01 PI vs. NRTI
Fat Mass (%)		16.5±1.11*	15.25±0.97	13.5±0.78	*P<0.05 PI vs. therapy-naive

Other Findings

PI patients had higher total cholesterol, low-density lipoprotein, triglyceride and free fatty acid concentrations compared with the therapy-naive or NRTI groups (P<0.01).
High-density lipoprotein levels were lower in the PI group compared with the therapy-naive or NRTI groups (P<0.05).
Body fat distribution analysis. 72 patients (46.75%) were considered clinically normal. 82 patients (53.25%) had alteration in body fat distribution, 34 patients (15.89%) were classified in the lipoatrophy group, nine (4.21%) in the obesity group and 39 (18.22%) in the mixed group. All these were receiving PI or NRTI.
Fat mass, mid-arm circumference, biceps, triceps and supra-iliac skinfold thicknesses were all lower in the lipoatrophy group compared with the mixed, obese and control groups (P<0.01 to P<0.0001). Waist-to-hip ratio was similar across all groups.
Intra-abdominal fat area values were significantly higher in the mixed and obese patients as compared with the lipoatrophy and control patients (P<0.05 to P<0.0001).

Author Conclusion:

Three major types of fat distribution abnormalities may occur in isolation or in association in HIV-infected patients undergoing active antiretroviral therapy: lipatrophy, which might be related to stavudine therapy; a mixed or fat redistribution syndrome related to an unusual side-product of effective virus control; and a subcutaneous adiposity syndrome reflecting an increase in caloric intake.

Funding Source:

Other:

Not specified

Reviewer Comments:

Placement of patients into one of four groups [lipoatrophic (fat wasting), obese, mixed symptoms of fat wasting and fat accumulation, and patients without any changes (control subjects)] was based on subjective assessment by investigators, and the authors noted that there was wide variability in investigator opinion regarding assessment of changes in body fat. A large portion of this study dealt with comparing differences among these groups. The number of patients in each group was rather small (34 in lipoatrophy group, nine in the obesity group and 39 in the mixed group).

Data on nutrient intake was collected, but results from this data were not reported; yet, one of their conclusions was that some HIV patients have "subcutaneous adiposity syndrome reflecting increase in caloric intake".

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?		Yes
	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?	Yes
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)	No
	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.)	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.)	N/A
	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?		???
	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%.)	???
	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?		No
	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?	???
	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?	Yes
	6.6.	Were extra or unplanned treatments described?	No
	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?	Yes
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?	???
	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?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes