Body composition in clinically stable men with HIV infection

Body Composition in Clinically Stable Men With HIV Infection Christine Grady, PhD, RN, Mary Ropka, PhD, RN, FAAN, Robin Anderson, MBA, RN, and H. Clifford Lane, MD

Clinically stable HIV-infected men (N = 106) receiving investigational antiretrovirals were recruited. Subjects were divided into three HIV disease severity groups by CD4+ cell count.

Christine Grady, PhD, RN, is Acting Chief; Mary Ropka, PhD, RN, FAAN, is Guest Researcher;and Robin Anderson, MBA, RN, is Research Nurse Specialist, Clinical Therapeutics Laboratory, National Institute of Nursing Research, National Institutes of Health, Bethesda, MD. H. Clifford Lane, MD, is Clinical Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Standard measures of body composition were assessed, as well as serum measures of visceral protein stores and kilocalorie intake. Group 1 subjects (CD4+ T cells<200) had significantly lower measures of body fat as compared with Group 2 (CD4 between 200 and 600) and Group 3 (CD4>600) despite adequate kilocalorie intake. Group 2 and Group 3 were not significantly different from each other. Our entire cohort had significantly lower muscle mass compared to norms. Our data demonstrate that people with advanced HIV disease have reduced muscle and fat.

Key words: Body composition, HIV infection, nutrition

JANAC

Vol. 7, No. 6, November-December, 1996

C h a n g e s in nutritional status, ranging from minor involuntary weight loss to significant wasting and malnutrition, are common in the HIV-infected individual. Although severe wasting usually occurs late in the HIV disease trajectory, unintentional weight loss is often an early and troublesome symptom. Lean body mass depletion and low serum albumin have been associated with m o r b i d i t y and m o r t a l i t y in some AIDS patients (Chlebowski, Grosvenor, Bernhard, Morales, & Bulcavage, 1989; Geunter et al., 1993; Kotler, Tierney, & Pierson, 1989). Severe weight loss, changes in body composition, especially lean body mass, decreases in serum protein levels, and decreases in serum levels of lipids and micronutrients all have been reported in HIV infection (Chlebowski, et al., 1989; Dworkin, Wormser, & Rosenthal, 1985; Grunfeld et al., 1992; Kotler, Wang, & Pierson, 1985; Macallan et al., 1993; Ysseldyke, 1991). HW wasting, defined as profound involuntary weight loss of greater than 10% of baseline body weight plus either chronic diarrhea or chronic weakness and documented fever in the absence of other possible causes, is a part of the Centers for Disease Control and Prevention surveillance case definition for AIDS (CDC, 1987). HIV wasting is the second most commonly reported AIDS diagnosis for men and women in the U.S. (Nahlen et al., 1993). The accompanying anorexia, weakness, and fatigue can have a profound impact on an individual's ability to f u n c t i o n a n d quality of life (Turner, Muurahainen, Terrell, Graeber, & Kotler, 1994). Additionally, the relationship between nutrition and immune function (Chandra, 1988) suggests that malnutrition 29

Body Composition in Clinically Stable Men With HIV Infection

could contribute to immune decline, facilitate the establishment of infectious complications and thereby promote HIV disease progression (Moseson et al., 1989). The consequences of malnutrition, although not well understood (Kotler, 1995), also could include neuropsychological changes, altered drug metabolism affecting effectiveness of therapy (Grosvenor, 1992), diminished quality of life (Turner et al.), increased risk of hospitalization (Cohan, Muurahainen, Geunter, Kosok, & Turner, 1992), and reduced survival (Chlebowski et al., 1989; Geunter et al., 1993; Kotler et al., 1989). The etiology of weight loss and malnutrition in general is thought to be multifactorial. Postulated mechanisms of weight loss include: inadequate dietary intake, reduced intestinal absorption, increased excretion of nutrients, increased metabolism or host requirements, and the acute phase response due to infection (Keusch & Thea, 1993; Sharkey, Sharkey, Sutherland, Chursh, & GI/HIV study group, 1992). Numerous review articles and observational studies have described nutritional changes in patients with late stage HIV disease or AIDS (Kotler et al., 1985; Macallan et al., 1993; Trujillo et al., 1992; Ysseldyke, 1991); fewer have examined the nature and timing of nutritional changes earlier in HIV disease (Keithley, ZeUer, Szeluga, & Urbanski, 1992; McCorkindale, Dybevik, Coulston, & Sucher, 1990; Ott et al., 1993; Parisien, Gelinas, & Cossette, 1993). In AIDS, weight loss and major changes in body composition have been attributed to depletion of b o d y cell mass (BCM) (Kotler et al., 1989), although changes in fat content also have been reported (Grunfeld et al., 1992; Kotler et al., 1985; Parisien et al., 1993). The exact mechanisms, timing, and underlying causes of this depletion of BCM that leads to wasting in AIDS are unknown. Most BCM depletion has been reported in late disease, although several recent reports suggest that HIV-infected people may lose BCM early in the disease (Ott et al., 1993; Suttman, Ockenga, Hoogenstraat, Deicher, & Muller, 1995). Nutritional intervention has been recommended at all stages of HIV disease (position of American Dietetic Association & Canadian Dietetic Association, 1994) 30

because of the impact of malnutrition on immune function and the significant physical and emotional burden of wasting and malnutrition for HIV infected people. In order to prevent weight loss and nutritional changes, interventions should be based on an understanding of what changes occur and when. A few studies have examined which nutritional interventions make a difference in clinical outcomes of H1V disease or at what point these interventions should be initiated (Chlebowski et al., 1993; Chlebowski, Grosvenor, Lillington, Sayre, & Beall, 1995; Kotler, Tierney, Culpepper-Morgan, Wang, & Pierson, 1990; McKinley, Goodman-Block, Lesser, & Salbe, 1994; Von Roenn, 1994; ). In an effort to better understand nutritional changes across the spectrum of H1V infection, we examined body composition in a cohort of ambulatory HIV-infected males who represent a wide range of disease severity as reflected by CD4+ T cell count. We looked at differences in body composition as they related to severity of HIV disease, using the CD4+ T cell count as a marker of extent of disease. We also considered the relationship of dietary intake and serum markers associated with nutritional status to body composition. In this cross- sectional, observational study, our purpose was to characterize differences in body composition observed in HW-infected men at several stages of HIV disease as evidenced by CD4+ T cell count. Methods Sample Selection

Male participants of HIV clinical studies sponsoKod by the National Institute of Allergy and Infectious Diseases (NIAID) and conducted in the HIV Clinic of the Warren G. Magnuson Clinical Center of the National Institutes of Health (NIH) were invited to participate. Those subjects who had been participating in a treatment trial for less than four months were eligible for inclusion. Subjects were purposefully recruited into strata representing three disease severity groups according to CD4+ T cell count range. Group 1 was composed of patients with JANAC

Vol. 7, No. 6, November-December, 1996

fewer than 200 CD4+ T cells/ram 3 representing late stage advanced disease or AIDS (CDC, 1987) and vulnerable to opportunistic diseases; Group 2, representing midstage disease, vulnerable to clinical and immunologic change, was made up of individuals with between 200 and 600 CD4+ T cells/mm3; and Group 3 comprised patients with greater than 600 CD4+ T c e l l s / 1 T l I n 3 representing early HIV disease. Exclusion criteria included: (1) pre- existing co- morbid conditions that might alter nutritional status, such as thyroid disorders, diabetes mellitus, and Crohn's disease; or (2) the use of total parenteral nutrition. The study was approved by the Institutional Review Board of the NIAID. Informed consent was obtained from all participants. W'flling subjects were then followed longitudinally for up to three years.

Procedures and Measures Body composition. All methods of assessing body composition in living people are indirect and include anthropometry, densitometry, isotope dilution techniques, and bioelectric impedance analysis. Most of these measures of body composition are based on a model in which the body is divided into at least two distinct compartments: fat and fat-free mass (FFM). The fat compartment consists of essential lipids and general storage fat. FFM consists of skeletal muscle, nonskeletal muscle and soft lean tissues, and the skeleton. Body muscle, a major component of FFM, serves as the major protein store of the body (Gibson, 1990). In assessing body composition, the following anthropometric data were recorded by trained observers using standardized procedures: height, weight, mid-arm circumference, triceps, and subscapular skin folds. From these, body mass index and mid-arm muscle area were calculated. Percentage of body fat and lean body mass were estimated by bioelectric impedance analysis (BIA). Food intake data and serum chemistries associated with nutritional status were also obtained. The Karnofsky performance scale was used to estimate functional status in t h e s e subjects (Mor, Laliberte, Morris, & Wiemann, 1984). JANAC

Vol. 7, No. 6, November-December, 1996

Height and weight. Standing height was measured once, to the nearest 0.5 cm, without shoes, using a stadiometer. Weight was measured to the nearest 0.1 kg, with clothes but without shoes, by use of a calibrated electronic scale. Calibration of the scale was performed before each use. Body mass index (BMI) or Quetelet's index was calculated for each subject using the following formula: weight (kg)/height (m) 2 (Gibson, 1990; Frisancho, 1990). Skinfold measurements. Skinfold thickness measurements provide an estimate of the size of subcutaneous fat stores that can be used to estimate total body fat (Gibson, 1990). Skinfolds was measured to the nearest 0.5 mm at t w o s t a n d a r d sites using Lange skinfold calipers. Subjects were instructed to stand with their arms hanging loosely at their sides. Measurement at each site was recorded three times in quick succession and the average of the three readings calculated. Triceps skinfolds (TSFO were measured on the posterior right arm at a level midway between the acromium process and the tip of the olecranon process. Subscapular skinfolds were measured on a pinch of skinfold approximately 1 cm below and lateral to the inferior angle of the right scapula. To increase reliability, skinfold measurements were consistently performed by a single trained study nurse. Mid-arm circumference. Mid-arm circumference (MAC) was measured to the nearest 0.1 cm using a flexible, metric, non- stretch tape. The midpoint between the acromium and the olecranon process was marked while the subject's right arm was bent at a 90-degree angle. The MAC measurement was taken with the ann hanging loosely at the subject's side. Mid-arm muscle area (MAMA). This measure, used to assess total body muscle mass, was calculated from previous anthropometric measures using the following formula: M A M A = [MACcm-(Triceps s k i n f o l d average~mXX)]2/(4x) (Gibson, 1990). Using Heymsfield's revised equation to correct for bone and neurovascular tissue, 10 cm 2was then subtracted for these male subjects (Heymsfield, McManus, Smith, Stevens, & Nixon, 1982). Bioelectric impedance analysis (BIA). Tetra-polar bioelectrical impedance was measured using RJL System 101 plethysmography with four self-adhering electrodes 31

Body Composition in Clinically Stable Men With HIV Infection

placed on the distal surfaces of the hands and feet according the RJL Systems r e c o m m e n d a t i o n s (RJL Spectrum BodyComp II-Version 1.5 Operations and Instructions Manual). Whole body electrical impedance measures resistance to an electric current and is commonly used to assess b o d y composition by applying s t a n d a r d r e g r e s s i o n e q u a t i o n s (Gibson, 1990). Percentages of lean body mass, body fat, body water, and a lean- to- fat ratio were estimated. Other nutrition-relatedmeasures. Blood was drawn to determine serum levels traditionally used for nutritional assessment and indicative of visceral protein stores i n c l u d i n g transferrin, a l b u m i n , a n d p r e a l b u m i n . Albumin levels were processed in the Clinical Pathology laboratory of the Warren G. Magnuson Clinical Center, NIH. Transferrin and p r e a l b u m i n were p r o c e s s e d through a contract laboratory with Smith Kline Beecham. Subjects were not required to be fasting. Each subject was individually instructed in the keeping of food records by a dietician who was experienced in nutrition research and trained in the use of the Minnesota Nutrition Data System dietary analysis (Version 2.1). Subjects recorded all intake over a threeday period, including one weekend day, in the week prior to their clinic visit. Completed records were carefully reviewed with each participant by the research dietitian in clinic to provide clarification on incomplete data. Subjects were requested to bring in bottles of all vitamins, minerals, and other supplements, so that informarion could be used in the assessment. Food records were sent for analysis of macro and micronutrients by the University of Minnesota Nutrient Data System. Absolute CD4+ T cell counts and relative percentages were determined through flow cytometry by the Clinical Immunology Services of the Frederick Cancer Research and Development Center.

Statistical Methods All subjects were grouped into one of three categories based on CD4+ T cell counts. Historical counts were used in some cases in patients with prior CD4+ T cell counts 32

well under 200 cells/mm 3because counts were not always available at the time of anthropometric assessment. To examine the relationship between body composition and CD4 group, body composition measures were compared across the three categories of HIV severity using analysis of variance models. For descriptive purposes, the percent of patients with CD4 counts under 200 cells/ram 3 (Group 1) was calculated within quintiles of the body composition measures. Logistic regression models also were used to assess the relationship between each body composition measure, and the o d d s of being in the less than 200 cells/ram 3 group was estimated by comparing patients at the 20th percentile of a body composition measure to patients at the 80th percentile. A relative odd that exceeds one implies that patients with the lower body composition value (at the 20th percentile) are more likely to be in Group 1 than those at the 80th percentile.

Results One h u n d r e d and seven HIV-infected men were recruited to participate in this study. One subject was excluded from the analysis because he was started on TPN during the study (N = 106). Characteristics of the study sample are found in Table 1. The majority of subjects were deliberately recruited from two randomized controlled treatment trials, one comparing zidovudine (AZF) to interferon-o~, and the other evaluating the combination of didanosine (ddI) and interferon-o~. Subjects were recruited into three strata according to CD4+ T cell count at the time of entry to this study. Group I (with CD4+ T cell counts<200 cells/mm 3) consisted of 31 men. The mean CD4 count (mean = 67, n = 9) for Group I was calculated using only values available from the date of anthropometry. Examination of CD4 values obtained near the time of their first nutrition study visit (most prior to the first visit) showed that the vast majority of this group (88%) actually had a CD4+ T cell count below 100 cells/ram 3. Group 2 (CD4+ T cell counts between 200 and 600 c e l l s / n a l n 3) consisted of 43 men, and Group 3 consisted of 32 men with CD4+ T cell counts of >600 JANAC

Vol. 7, No. 6, November-December, 1996

I

Table 1. Characteristics of the S t u d y S a m p l e Range in C D 4 Count (cells/mm ~) Characteristics

Less than 200 (N = 31)

200 to 600 (N = 43)

More than 600 (N = 32)

Total (N = 106)

9 CD4 count (cells/ram9 Mean _+SD Range

67 • 34 30 - 144

436 _+105 229 - 599

761 _+138 602 - 1217

520 :a 247 30 - 1217

9 Age (years) Mean _+SD Range

36 • 6 25 - 48

35 _+7 2I - 55

34 + 8 21 - 56

35 + 7 21 - 56

71 22.6 6.5 0

83.7 11.6 4.7 0

90.6 3.1 3.1 3.1

82.1 12.3 4.7 0.9

87.0 • 11

95.5 • 7

92.4 _+13

92.1 _+11

9 Race (%) White Black Hispanic Other Karnofsky Score

c e l l s / r a m 3. D e s p i t e the r a n g e in d i s e a s e s e v e r i t y as reflected by CD4 count, all subjects were ambulatory and seen in the outpatient clinic. Only 11 subjects (9.6%) had active opportunistic infections (including Mycobacterium avium (n = 3), Pneumocystiscariniip n e u m o n i a (n = 3), and cryptosporidiosis (n = 5) at the time of the study. These 11 subjects were all in G r o u p 1. In contrast to age, which was similar across CD4 groups, race varied primarily b y the percent of patients in each g r o u p w h o were African-American. African-Americans comprised nearly 25% of G r o u p I and 14% of G r o u p 2, while only one African-American had a CD4 count above 600 cells/ruraL The authors believe this distribution is the consequence of strategies and difficulties in the recruitment of research subjects, and not an indication of lower CD4+ cells among HIV- infected African-Americans. Table 2 p r e s e n t s the m e a n b o d y c o m p o s i t i o n m e a s u r e s (_+ s t a n d a r d d e v i a t i o n ) a c c o r d i n g to the t h r e e defined CD4+ cell groups. M e a n heights were similar across groups. All m e a s u r e s of b o d y composition estimating b o d y fat, including BMI, triceps and subscapular JANAC

Vol. 7, No. 6, November-December, 1996

skinfolds, and percent b o d y fat were significantly lower in patients in Group 1, as compared with the other categories. MAMA, a measure of FFM muscle, also was sign i f i c a n t l y l o w e r in G r o u p 1 t h a n the o t h e r g r o u p s . Groups 2 and 3 were not significantly different from each other on the same b o d y composition measures. In a d d i t i o n to the significant differences b e t w e e n G r o u p I and the other two CD4 groups on each measure of b o d y composition, there was deviation from age and sex matched n o r m s ( N H A N E S I and II) for s o m e b o d y composition measures. Mean BMI is significantly less for each g r o u p of m e n in G r o u p s 1, 2, and 3 as c o m p a r e d w i t h m e a n BMI (25.8 + 4.0) for m e n in the s a m e a g e r a n g e f r o m t h e N H A N E S I a n d II d a t a (p<0.01) (Frisancho, 1990). TSF m e a s u r e m e n t for m e n in G r o u p 1 is significantly less than TSF n o r m for m e n of the same age (13.0ram _+6, p<0.01) (Frisancho). Muscle mass, as estimated by MAMA, was significantly less in the entire HIV group within each range of CD4 count as compared w i t h m e n of the s a m e a g e (55.1 c m z + 11.6, p<0.001) (Frisancho). In fact, the m e d i a n M A M A in this cohort 33

Body Composition in Clinically Stable Men With HIV Infection

Table 2. Average Body Composition Measures by RANGE of CD4 Count Men Only Range in CD4 Count (cells/mm3) Body Less than Composition 200 Measure (31) 1 9 Height (m)

200 to 600 (43)

More than 600 (32)

Age/Sex Matched Norms 4

w a s 41.5 c m 2, w h i c h represents only the 10th percentile of the n o r m (Frisancho, 1990). Table 3 sunmlarizes the relative odds of being in G r o u p 1 at the 20th percentile of a b o d y c o m p o s i t i o n m e a s u r e versus patients at the 80th percentile. As univariate predictors ( s h o w n in the u n a d j u s t e d c o l u m n ) of the o d d s of being in the low CD4 group, all are statistically significant. Patients at the 20th percentile of BMI have a sixfold excess (p<0.001) in the o d d s of being in the l o w C D 4 g r o u p as c o m p a r e d to patients whose BMI is at the 80th percentile. There is a seven- to eightfold excess in the odds of being in

1.76

1.78

1.75

(0.06)2

(0.06)

(0.08)

9 Weight (kg)

66.0 (10.5)

76.4~ (11.0)

74.5~ (14.2)

9 Body mass index

21.4 (3.1)

24.2w (3.4)

24.1:~ (3.2)

25.8 (4)

9 Triceps skin fold (ram)

10.1 (4.5)

14.8~ (6.0)

15.7w (5.9)

13.0 :~ (6)

14.1 skin fold (mm) (5.4)

16.8"t (5.7)

17.0f (4.8)

Body composition measure

9 Subscapular

Table 3. Relative Odds of a CD4 Count Less Than 200 for Patients at the 20th Percentile of a Body Composition Measure as Compared to Patients at the 80th Percentile: Men Percentile 20th 80th

Relative Odds Unadjusted Adjusted 1

9 % body fat3

13.7 (5.4)

17.2f (5.6)

17.5~ (5.8)

9 Body mass index

20.2

26.2

6.4 w (2.2, 18.6) 2

1.1 (0.1, 18.5)

9 Lean- fat ratio

8.0 (5.4)

5.5:~ (2.5)

5.4:~ (2.2)

9 Triceps skinfold

7.7

18.3

7.7 w (2.6, 22.1)

9.3 f (1.0, 83.8)

9 Mid-arm

38.8 (9.9)

44.9~ (9.5)

42.2 (8.8)

9 Subscapular skinfold 11.3

21.7

3.1 t (1.2, 8.0)

0.2 (0.0, 1.1)

9 % body fat

11

21

3.5 ~: (1.4, 8.3)

0.4 (0.0, 4.2)

9 Lean fat ratio

3.8

8.1

0.4 :~ (0.2, 0.8)

0.4 (0.1, 1.6)

tSignificantly different from patients with CD4 counts less than 200 (p<0.05)

9 Weight

62

83

5.7 w (2.0, 16.0)

2.4 (0.3, 21.8)

:~Significantly different from patients with CD4 counts less than 200 (p<0.01)

9 Mid- arm muscle circumference

34.3

50.8

2.6 f (1.2, 5.6)

1.9 (0.4, 8.0)

muscle area (cm2)

55.1"* (11.6)

1Sample size 2Standard deviation 3From bioetectric impedance analysis 4NHANES I & II (Frisancho)

w different from patients with CD4 counts less that 200 (p<0.001) **Significantly different at all CD4 groups (p< 0.01)

34

1Adjusted for the other body composition measures 295% confidence interval #Significantly different from one (p<0.05) :~Significantly different from one (p<0.01) w different from one (p<0.001) JANAC Vol. 7, No. 6, November-Decembel; 1996

the low CD4 group at the 20th percentile of TSF as compared to those at the 80th percentile (p<0.001). Similar comparisons on the other measures yield excesses in the odds of being in group 1 from approximately three- to sixfold in the lower versus the higher percentile. Although all the body composition measures displayed in Table 3 have a relationship with the odds of being in Group 1, it is of interest to determine if any of the meastues has a residual relationship with the CD4 group, which is not accounted for by another measure. 19o the measures of body composition appear equally useful or important in characterizing the anthropometric status of HIV-infected men? Except for TSF, the other body composition measures appear to form useful proxies for each other. Examining the adjusted relative odds in Table 3, all become statistically insignificant after control for the information contained in the other body composition measures. In contrast, TSF remains significantly related to the odds of being in the low CD4 group (p<0.05) in the presence of other body composition measures. This suggests that TSE a measure of body fat, contains unique information that is able to characterize body composition of HIV-infected individuals. Serum levels of albumin, prealbumin, and transferrin were within normal limits for all three groups. No statistically significant differences were observed between the three groups as shown in Table 4. Kilocalorie intake does not correlate with differences in body composition in this cohort. Of the 106 subjects, 94 completed three-day food records in the week prior to obtaining body composition measures. Intake from the three days was averaged for each individual and intake analysis performed. By total daffy kilocalorie intake or by kilocalories per kilogram (shown in Table 4), there were no significant differences between the three CD4 groups. Discussion

Our data support previous observations that lower weight and less lean body mass and muscle are common in people with advanced HIV disease. In this cohort, even those with "early HW disease" as defined by CD4+ T cell count had significantly less muscle mass compared JANAC

Vol. 7, No. 6, November-December, 1996

Table 4. Nutrition Study Measures ~,;: ;4J~:~

!;~; ~:iii i;~:!~~ ~"?~' :~ ~:~:~: ~:;: i,~'~;~i ~:~ ,~

Range in CD4 Counts (r Other Measures Less than 200 200-600 (31) (43)

9 Energy (kCal/kg)

39.6 (12)*

36.3 (13)

3) More than 600 (32)

34.5 (13)

9Serum albumin 4.3 4.3 4.3 (g/dl) (0.4) (0.3) (0.3) ~1~!~;~!~1!!~!!~i~!~i!~i!!i!i!~!~!~i!~i~i!i!~i]i~i]i~]~i~i:~i;~i~i~i~i~i~i~i~i~i~i~i~U~!~Mi!~i!~i!~!~!~i!~!~!~!~!~!i~!~i!!i~i!~!i~!~!!Ui~;iJ!i~!i~!~i~iJiH~;~!ili~ ~i!~!i~!~i~i~i~ *Standard deviation to age and sex matched norms. This has been demonstrated by others using BIA to demonstrate reduced body cell mass (Ott et al., 1993; Suttman et al., 1995). In addition to decreased muscle mass, our data show that people with a d v a n c e d HIV disease also have decreased fat stores compared to those with HW infection who are at earlier stages of disease as reflected by CD4+ cell count. Although changes in fat content have been reported before (Kotler et al., 1985; Sharkey et al., 1992; Parisien et al., 1993), in these other studies it was associated with decreased energy intake, whereas in this cohort, mean kilocalorie intake in those with diminished fat was no different from kilocalorie intake in those with normal body composition, and was adequate in all groups (Chlebowski et al., 1995). Diminished fat stores, demonstrated by anthropometric measures of TSF, as well as estimated percent fat from BIA, when observed clinically are quite impressive in some individuals. Others have reported declining weights, decreased lean body mass (especially BCM) and decreased visceral protein stores associated with decreased intake (CDC, 1987; Chlebowski et al., 1995; Keithley et al., 1992). In contrast, despite some cases of very low MAMA values and reduced fat stores, measures of visceral protein stores were normal in this cohort. In addition, kilocalorie intake appeared adequate and was not different in those who had lower CD4 counts or lower percentages of fat or muscle. Despite their seemingly adequate kflocalorie intake, we noted reduced weight and BMI, and reduced fat and muscle stores, in those with more advanced disease. 35

Body Composition in Clinically Stable Men With HIV Infection

As mentioned earlier, there are several causes of changes in weight and b o d y composition in illness including dietary intake, decreased absorption, and increased utilization and metabolism. In HIV infection, all three are postulated to be at work, and changes in nutritional status and malnutrition are believed to be multifactorial and not simple. Keusch and Thea (1993) suggest that nutritional changes in HIV infection could be understood as an overlap between endogenous and exogenous pathophysiologic processes. Voluntary or involuntary reduction in intake that leads to insufficient calories and nutrients to meet an individual's needs are part of an exogenous process, which impacts nutrition. Decreased dietary intake so that food taken in was insufficient to meet an individuals nutritional needs could be due to anorexia, mouth sores, difficulty swallowing, economics, ignorance, fatigue, lack of assistance with shopping or cooking, or combinations of the above. Keusch and Thea (1993) also include malabsorption in the exogenous paradigm because it contributes to the unavailability of nutrients. Studies have demonstrated decreased kilocalorie intake in advanced HIV disease, especially in those with secondary infections (CDC, 1987; Geunter et al., 1993; Keithley et al., 1992; MacaUan et al., 1993). A recent study by Macaltan and colleagues (1995) shows a strong positive relationship between rate of weight loss and energy intake. In our cohort, although there was variability in intake and many of the above factors apply, the group with AIDS consumed as many kilocalories as the other groups. The mean kilocalorie/kg intake in the small number of patients with secondary infections was actually higher (44.7 kflocalories/kg) than in those without secondary infections. Impaired intestinal absorption, another reason for weight loss, has been documented in HIV infection (Ott et al., 1993). In this cohort, only 13 of the 106 (12.3%) reported diarrhea, and of those, 42% were in Groups 2 and 3. The other paradigm for malnutrition is characterized as an e n d o g e n o u s process in which metabolic rate increases and catabolism predominates over anabolism (Keusch & Thea, 1993). It is believed that this process is probably triggered by various cytokines in response to

36

infection, trauma, stress and other factors. Previous studies advance this paradigm as operative in HIV disease, especially AIDS, because of the p r e d o m i n a n t depletion of body cell mass (Kotler et al., 1985, 1989; Ott et aL, 1993) and higher than expected resting energy expenditures (REE) measured by indirect calorimetry (CDC, 1987; Hommes et al., 1991; Melchior et al., 1991). Using measures more readily available to clinicians, we were able to s h o w significantly lower muscle mass compared to age-matched norms in all HIV-infected men studied, and those in the lowest CD4+ group had significantly lower muscle mass than the other two groups. Demonstrated variation in body composition in this cohort support the hypothesis that endogenous processes, which may be due to HIV infection itself, begin to have effects on body composition early in HIV disease. As H I V - i n f e c t e d i n d i v i d u a l s b e c o m e m o r e immunologically compromised and clinically more symptomatic, other factors, possibly including anorexia, reduced calorie intake, and malabsorption (although we were not able to demonstrate these), may begin to have an effect, so that people' with advanced disease, even without active secondary infection, often have significant reduction in body weight which includes expenditure of both muscle mass and fat. Although it may be true that "problems of malnutrition are essentially independent of immune depletion" (Kotler, 1995, p. 14) it a p p e a r s that they nonetheless parallel changes in immune function. In addition, in this study, differences in muscle and fat were demonstrated by simple, non-invasive anthropometric measures (skinfotds thickness, MAC, and calculated MAMA), which are easy to perform and inexpensive. Although there is some expected margin of error assumed in these measures (Gibson, 1990), the use of a single trained examiner greatly reduces measurement error, and the trends in this sample are clear and differences are highly statistically significant. In this cohort, TSF measurement seems to contain unique information that is able to characterize body composition in HIV infection.

JANAC Vol.7, No. 6, November-Decembe~1996

Conclusion

Chandra, R. (1988). Nutritional regulation of immunity. In R. Chandra (Ed.), Nutrition and immunology (pp. 1-7). New York: Alan Liss, Inc.

Weight differences and other body composition alterations are con'anon in HIV infection, begin early, and ultimately encompass changes in muscle and in fat. Our data suggest that measurement of TSF and MAC (and the subsequent calculation of MAMA) may be simple measures that, along with weight (Grtmfeld & Feingold, 1993), can help predict changes in body composition in HW-infected individuals over lime. Prospective cohorts of HIV- infected individuals at different states of disease should be followed longitudinally to see if these observations play out. Weight loss, changes in body composition, and other nutritional changes can contribute to the complex physical and psychological burdens experienced by people with AIDS and H1V disease. Clinical interventions to effectively prevent or reverse changes in nutritional status should be based on an adequate understanding of the nature and timing of these changes. Without such understanding, interventions may be misguided, wasteful or even burdensome in themselves. Data about changes in body composition, such as those obtained in this study, will assist in the development and evaluation of targeted interventions. Additionally, clinicians need simple, inexpensive methods of measuring and assessing changes in nutritional status to determine the appropriate time to initiate certain interventions. We have demonstrated significant differences in body composition in those with more advanced HIV disease using non-invasive techniques transportable to any healthcare setting. Nurses and other healthcare professionals responsible for the care of people with H1V disease aim to reduce suffering and maintain optimal functioning as long as possible. Assessment, monitoring and appropriate intervention to forestall serious and potentially life- threatening changes in nutritional status is an important part of this responsibility.

Chlebowski, R., BeaU, G., Grosvenor, M., Lillington, L., Weintraub, N., Amber, C., Richards, E., Abbruzzese, B., McCamish, M., & Cope, E (1993). Long-term effects of early nutritional support with new enterotropic peptide- based formula vs. Standard enteral formula in H1Vinfected patients: Randomized prospective trial. Nutrition, 9, 507- 512.

References Centers for Disease Control and Prevention. (1987). Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. Morbidity and Mortality Weekly Reports, 36(supp 2S), 3S-15S.

JANAC

Vol. 7, No. 6, November-December, 1996

Chlebowski, R. Grosvenor, M., Bernhard, N., Morales, L., & Bulcavage, L. (1989). Nutritional status, gastrointestinal fllnction, and survival in patients with AIDS. AmericanJournalof Gastroenterology,84,1288-1293. Chlebowski, K, Grosvenor, M., Lillington, L., Sayre, J., & Beall, G. (1995). Dietary intake and cotmseling, weight maintenance, and the course of HIV infection. Journalof the American DieteticAssociation,95, 428- 435. Cohan, G., Muurahainen, N., Geunter, E, Kosok, A., & Turner, J. (1992). HIV related hospitalizations, CD4 percent, and nutritional markers. VIII International Conference on AIDS, Amsterdam, Abstract #POB7113. Dworkin, B., Wormser, G., & Rosenthal, W. (1985). Gastrointestinal manifestations of the acquired immunodeficiency syndrome. American Journalof Gastroenterology,80, 774-778. Frisancho, A. (1990). Anthropometric standards for the assessment of growth and nutritional status. Ann Arbor: The University of Michigan Press. Geunter, P., Muurahainen, N., Simons, G., Kosok, A., Cohan, G., Rudenstein, R., & Turner, J. (1993). Relationship among nutritional status, disease progression, and survival in H1V infection. Journal of Acquired Immunodeficiency Syndrome, 6, 1130-38. Gibson, R. (1990). Principles of nutritional assessment. New York: Oxford University Press. Grosvenor, M. (1992). Nutritions in HIV infection: Concepts and strate~es. The AIDS Reader,2, 165-180. Grunfeld, C., & Feingold, K. (1993). Body weight as essential data in the management of patients with human immunodeficiency virus infection and the acquired immunodeficiency syndrome. American Journal of Clinical Nutrition, 58, 317-318. Grunfeld, C., Pang, M., Shimuzu, L. Shigenaga, J., Jensen, P., & Feingold, K. (1992). Resting energy expenditure, caloric intake, and short-term change in HIV infection and AIDS. American Journal of Clinical Nutrition, 55, 455-460. Heymsfield, S., McManus, C., Smith, J., Stevens, V., & Nixon, D. (1982). Anthropometric measurement of muscle mass: Revised equations for calculating bone-free arm muscle area. American Journal of Clinical Nutrition, 36, 680-690. Hommes, M., Romijin, J., Endert, E., et al. (1991). Resting energy expenditure and substrate oxidation in human immunodeficiency virus infected asymptomatic men: H1V affects host metabolism in the early symptomatic stage. AmericanJournalof ClinicalNutrition, 54, 311-315. 37

Body Composition in Clinically Stable Men With HIV Infection

Keithley, J., Zeller, J., Szeluga, D., & Urbanski, P. (1992). Nutritional alterations in persons with HIV infection. Image, 24, 183-189.

Nahlen, B., Chu, S., Nwanyanwu, O., Berkelman, R., Martinez, S., & Rullan, J. (1993).HIV wasting syndrome in the United States. AIDS, 7,183-188.

Keusch, G., & Thea, D. (1993). Malnutrition in AIDS. Medical Clinics of North America, 77, 795-814.

Ott, M., Lembcke, B., Fischer, H., J/iger, R., Polar, H., Geier, H., Rech, M., Staszewski, S., Helm, E., & Caspary, W. (1993). Early changes of body composition in human immunodeficiency virus- infected patients: Tetrapolar body impedance analysis indicates significant malnutrition. American Journal of Clinical Nutrition, 57, 15-19.

Kotler, D. (1995). HIV-associated malnutrition. Journal of Physicians Association in AIDS Care, 2, 12-15. Kotler, D., Tierney, A., Culpepper-Morgan, J., Wang, J., & Pierson, R. (1990). Effect on home total parenteral nutrition on body composition in patients with the acquired immunodeficiency syndrome. Journal of Parenteraland Enteral Nutrition, 14, 454-458. Kotler, D., Tierney, A., & Pierson, R. (1989). Magnitude of body- ceilmass depletion and the timing of death from wasting in AIDS. American Journal of Clinical Nutrition, 50, 444-447. Kotler, D., Wang, J., & Pierson, R. (1985). Body composition studies in patients with the acquired immunodeficiency syndrome. American Journal of Clinical Nutrition, 42,1255-1265. Macallan, D., Noble, C., Baldwin, C., Foskett, M., McManus, T., & Griffin, G. (1993). Prospective analysis of patterns of weight change in stage IV human immunodeficiency virus infection. American Journal of Clinical Nutrition, 58, 417-424. Macallan, D., Noble, C., Baldwin, C., Jebb, S., Prentice, A., Coward, A., Sawyer, M., McManus, T., & Griffin, G. (1995). Energy expenditure and wasting in human immunodeficiency virus infection. New England Journal of Medicine, 333, 83-88. McCorkindale, C., Dybevik, K., Coulston, A., & Sucher, K. (1990). Nutritional status of HIV-infected patients during the early disease stages. Journal of the American Dietetic Association, 90, 1236-41. McKinley, M., Goodman-Block, J., Lesser, M., & Salbe, A. (1994). Improved body weight status as a result of nutrition intervention in adult, HIV-positive outpatients. Journal of the American Dietetic Association, 94, 1014-1017. Melchior, J., Salmon, D., Rigaud, D., et al. (1991). Resting energy expenditure is increased in stable, malnourished HW-infected patients. American Journal of Clinical Nutrition, 53,437-441.

Minnesota Nutrition Data System Users Manual (Version 2.1). Minneapolis: Nutrition Coordinating Center, University of Minnesota. Mor, V., Laliberte, L., Morris, J., & Wiemann, M. (1984). The Karnofsky performance scale: An examination of its reliability and validity in a research setting. Cancer,53, 2002-2007.

Ott, M., Wegner, A., Caspary, W., & Lembcke, B. (1993). Intestinal absorption and malnutrition in patients with the acquired immunodeficiency syndrome. Gastroenterology,31,661-665. Parisien, C., Gelinas, M., & Cossette, M. (1993). Comparison of anthropometric measures of men with H1V: Asymptomatic, symptomatic, and AIDS. Journal of the American Dietetic Association, 93,1404-1408. Position of The American Dietetic Association and the Canadian Dietetic Association: Nutritional intervention in the care of persons with human immunodeficiency virus infection. (1994). Journal of the American Dietetic Association, 94, 1042-1045.

RJL Spectrum BodyComplI-Version 1.5 Operations and Instructions Manual. Detroit: RJL Systems Inc. Sharkey, S., Sharkey, K., Sutherland, L., Chursh, D., & the GI/HIV study group. (1992). Nutritional and food intake human immunodeficiency virus infection. Journal of Acquired Immunodeficiency Syndrome, 5, 1091- 1098. Suttman, U., Ockenga, O., Hoogenstraat, L., Deicher, H., & Muller, M. (1995). Incidence and prognostic value of malnutrition and wasting in human immunodeficiency virus-infected outpatients. Journal of Acquired Immunodefick,ncy Syndromeand Human Retro~'ruses,8, 239- 246. Trujillo, E., Borlase, B., Bell, S., Geunther, K., Swails, W., Queen, P., & Trujillo, R. (1992). Assessment of nutritional status, nutrient intake, and nutrition support in AIDS patients. Journal of the American Dietetic Association, 92,477-478. Turner, J., Muurahainen, N., TerreU, C., Graeber, C., & Kotler, D. (1994). Nutritional status and quality of life. Proceedings of the Xth International Conferenceon AIDS, Yokohama, Japan, 2, 35. Von Roenn, J. (1994). Randomized trials of megestrol acetate for AIDSassociated anorexia and cachexia. Oncology, 51 (suppl 1), 19-24. Ysseldyke, L. (1991). Nutritional complications and incidence of malnutrition among AIDS patients. Journal of the American Dietetic Association, 91,217-218.

Moseson, M., Zeleniuch-Jacquotte, A., Belsito, D., Shore, R., Marmor, M., & Pasternak, B. (1989). The potential role of nutritional factors in the induction of immunologic abnormalities in HIV- positive homosexual men. Journal of Acquired Immunodeficiency Syndrome, 2,235-247.

38

JANAC

Vol. 7, No. 6, November-December, 1996