EAL

H/A: Body Composition Measurement (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate whether factors influencing body composition may be unique for male and female adolescents with horizontal transmission of human immunodeficiency virus (HIV).

Inclusion Criteria:

Subjects were enrolled in the REACH Project of the Adolescent Medicine HIV/AIDS Research Network
Subjects were 12 to 18 years old, infected with HIV as teens primarily through sexual or substance use
These subjects were compared to age-matched, non-HIV infected controls with similar high-risk behaviors (sex and drug use)
All subjects had to sign informed consent.

Exclusion Criteria:

Subjects who were infected with HIV through perinatal transmission or contaminated blood products were excluded from the study.

Description of Study Protocol:

Recruitment

HIV-positive males and females were recruited into the REACH project according to previously reported methods.

Design

Case-control study, cross-sectional analysis of baseline data from a cohort study.

Intervention (if applicable)

Baseline self-reported data was collected for obtaining sensitive information (i.e., behaviors based on substance abuse and sexual behaviors)
Height, weight, BMI, fat mass and lean body mass were calculated at baseline
Skinfold measurements of the biceps, triceps, subscapular and suprailiac were obtained in triplicate and the mean of these three measurements was used
Mid-arm circumference (MAC) of the upper arm was also obtained
Muscle mass was calculated using MAC and tricep skinfold measurements. Fat-free mass was calculated.
The principle investigator at each testing site assessed the pubertal stage of the genitals and breasts using Tanner I to V categories
CD4 and T-cell lymphocyte counts were determined at each clinical site. Free testosterone for males and females was also measured. Dehydroepiandrostenedone-sulfate and androstenedione were measured for females as well.
Subjects hand-wrist bone-age was also assessed to measure stage of growth development using X-rays.

Statistical Analysis

The Kolmogorov-Smirnov test was used to assess for deviation from normality for BMI, muscle mass, fat mass and fat-free mass. As a result, fat mass and fat-free mass were log-transformed to address potential deviations from normality.
Univariate analysis with one-way non-parametric analysis of variance or parametric T-tests were used to assess Tanner stage, bone age, race, behavioral variables, hormonal contraceptive use, endocrine measurements, past pregnancy, irregular period and HIV-related indicators.
If statistical significance was noted, then comparison of subgroups within larger groups for categorical variables in linear regression analysis were undertaken.

Data Collection Summary:

Timing of Measurements

Baseline anthropomorphic measurements were obtained, including: Height, weight, bicep, tricep, subscapular and suprailiac skinfold measurements and midarm circumference. BMI, muscle mass, fat-free body mass and fat mass were calculated.

Dependent Variables

Height was measured with a standiometer
Weight was measured with a scale without undergarments
BMI was calculated
Fat mass was calculated using the following equation: Fat mass (kg) = weight (kg) x (94.95/D - 4.95), where D = density, was specified for males or females as listed in the methods section
Lean body mass was calculated with the following equation: (Mid upper arm circumference - π x triceps skinfold)/4π.

Independent Variables

HIV status
CD4
Treatment status
Viral load
Contraception
Substance use
Androgen levels
Appetite changes
Bone age.

Control Variables

Age, HIV status and bone age were measured to allow for comparison and control.

Description of Actual Data Sample:

Initial N

519 subjects (137 males, 382 females).

Attrition (final N)

519 Total
326 subjects were HIV-positive, 193 were HIV-negative
Females: 146 HIV-negative, 236 HIV-positive subjects
Males: 47 HIV-negative, 90 HIV-positive subjects.

Age

Average age for females was 16.55 years for HIV-negative subjects and 16.80 years old for HIV-positive (P=0.048)
Average age for males was 16.85 years for HIV-negative males and 17.20 years for HIV-positive (P=0.094).

Ethnicity

For females, comparing HIV-negative to HIV-positive subjects: 13% were White, non-Hispanic compared to 9%; 20% were Hispanic compared to 11%; and 67% were black non-Hispanic compared to 79%
For males, comparing HIV-negative to HIV-positive subjects: 17% were White non-Hispanic compared to 10%; 34% were Hispanic compared to 30%; and 49% were black non-Hispanic compared to 60%
Females had a larger percentage of black, non-Hispanic subjects in the HIV-positive group (79% vs. 67%) compared to the HIV-negative group (P=0.006). No other significant differences existed.

Other Relevant Demographics

A larger percentage of the male subjects had bisexual or homosexual experience at baseline (67.2% vs. 8.33%) compared to the females.

Anthropometrics

BMI and fat mass were greater for females than males (P<0.0001)
Muscle mass and fat-free mass were greater for males vs. females (P<0.0001)
Fat-free body mass was greater for HIV-positive females than HIV-negative females (P=0.03)
BMI, muscle mass and fat mass were significantly greater for HIV-negative females than HIV-positive females (P= 0.0169, 0.0123, and 0.0229, respectively) when controlling for CD4 counts
Fat mass was significantly greater in HIV-negative males than HIV-positive males (P=0.0192) when controlling for CD4 counts.

Location

Research took place at multiple primary care sites. Locations were not specified.

Summary of Results:

Table 3: Linear regression of predictors of anthropomorphic measurements, by gender adjusted least squares means for statistically significant predictors. ^a,b,c

N	Female				Male
	BMI	Log₁₀ Fat Mass	Log ₁₀ FFM	Muscle Mass	BMI	Log ₁₀Fat Mass	Log ₁₀ FFM	Muscle Mass
Testosterone-total (ng per dL)^d
25% (male 252, female 22)					23.8***	12.5****	55.8***
50% (male 291, female 33)					22.7***	9.9****	54.1***
75% (male 435, female 57)					21.7***	8.0****	52.3***
Testosterone free (ng per dL)^d
25% (male 3.5, female 0.2)	24.4****	11.9****	42.1**	3,981****
50% (male 4.3, female 0.4)	26.1****	12.7****	43.2**	4,294****
75% (male 6.2, female 0.6)	27.7****	13.6****	44.3**	4,607****
Androstenedione^d
25% (female 585.00)	19.8***			3,120**
50% (female 944.51)	19.0***			2,976**
75% (female 1,349.00)	18.1***			2,813**
CD4 counts
<200	21.3***	15.1**	44.7	3,431*
200 to 500	24.2***	17.0**	45.7**	3,710***
> 500 (ref)^e	27.4	20.0	47.9	4,441
Hormone contraceptive use
Medroxyprogesterone only			46.8*
OC only			46.7
No contraceptive (ref)^e			44.2
Race
Hispanic				3,630*	24.3*	10.7***
White and others				3,757	23.4	10.7*
Black non-Hispanic (ref)^e				4,194	22.0	7.7
Bone Age
Unknown	25.3*	17.0		3,959		8.7		5,259
> 17 years old	25.2**	18.6**		4,096		11.2*		5,124*
< 17 years old (ref)^e	22.3	16.2		3,526		9.1		4,358
HIV and treatment status
HAART with PI	24.2	17.8	45.7	3,850
ART	24.2	17.0	45.7	3,739
Not on treatment	25.9***	19.1***	49.0***	4,244**
HIV - (ref)^e	22.8	15.5	43.7	3,610
(HIV+) - (HIV-)^f	2.0*	1.2*	1.1*	334
(HIV+, no Rx) - (HIV+, ART or HAART)^f	1.7	1.1	1.1*	450*

^a *P<0.05; **P<0.01; *** P<0.001; **** P<0.0001; blank cells indicate the variables are not in the final mode (P>0.05) for corresponding outcome.

^b See methods for list of potential predictors and covariates.

^c Covariates for food consumption, depression and socioeconomic status were adjusted in the multiple variable regression models when they were significant at a level of 0.05. For males, lower maternal education was associated with lower BMI (P<0.01). For females, loss of appetite was associated with lower BMI (P<0.05).

^d Among the predictors, total testosterone, free testosterone and androstenedione were used as continuous variables in the model. For these predictors, the Least Square Means for each outcome are given for the gender-specific 25th, 50th, and 75th percentile values of the predictors.

^e (Ref) means reference group. For pairwise comparison among two groups for HIV treatment status, the differences of least square means were provided. TRT = treatment; ART = current ART therapy without HAART; HAART with PI = HAART with protease inhibitor. The interaction terms between CD4+ T cell counts and testosterone (both total and free) were tested, there were not statistically significant.

^f Difference of the least square means between two group were compared using the contrast procedure in GLM for the categories: HIV-positive vs. HIV-negative; HIV-positive without treatment vs. treatment.

Other Findings

Females demonstrated different associations than their male counterparts:

A higher BMI was associated with a higher free testosterone level, a lower androstenedione level, a higher CD4 T cell count and a positive HIV status
HIV-positive females without treatment had a higher BMI; thus, BMI may not be a reflection of treatment
Greater muscle mass was associated with a higher free testosterone, lower androstenedione level, higher CD4+ T cell counts and HIV-positive status
For HIV-positive status, muscle mass tended to be greater for females with no antiretroviral treatment.

For Males:

Higher BMI and greater fat mass were associated with a lower total testosterone
Race was associated with fat mass.

There was no significant interaction between androstenedione and free testosterone for BMI and muscle mass infection.

Author Conclusion:

Wasting was not a predominant characteristic of the REACH HIV-infected boy or girl cohorts as measured by fat or lean body mass.

HIV status was not associated with a lower muscle or fat mass.

Different factors influenced body composition for females than males. Total testosterone in males was inversely related to fat mass as well as lean body mass as measured by fat free mass.

Higher testosterone levels may be protective against loss in lean and fat mass in females. The higher fat-free body mass for adolescents on medroxyprogesterone implies that the androgenic components of hormonal contraceptives may also be protective against muscle loss.

Conclusions may be limited because of the use of skinfold thickness measurements to measure body composition; however, these problems were attempted to be overcome by use of mathematical models.

Funding Source:

Government:

National Institude of child Health and Human Development, National Institute on Ddrug Abuse, Allergy and Infectious Diseases and Mental Health, Adolescent Medicine HIV/AIDS Research Network

Reviewer Comments:

Method for sampling/obtaining subjects was described in a previously published study.

Blinding is likely not applicable in this observational study.

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?		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?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	???
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	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.)	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?	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%.)	N/A
	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?	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?	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