Abstracts Vol. 1 [International Conference on AIDS (11th: 1996: Vancouver, Canada)]

Mo.B. 1390 - Mo.B. 1394

Monday, July 8, 1996

Elevations in REE Pin HIVinfected women were comparable to those in men (I 12 and I 10%
of controls in HIV+ women and men, respectively). In women, as in men, this effect
appeared to be largely independent of stage of disease.
Conclusions: Progressive loss of fat and BCM, as well as hyperrnetabolism, are present in
HIV infected women, as well as men.There was no evidence of marked sparing of fat at the
expense of BCM in either gender:
Kathleen Mulligan, PnD, IJUCSF Dvision of Endocrinology, San Francisco General Hospital,
Bldg. 100, Room 321, 1001 Potrero Ave., San Francisco, CA, 941 10, USA.
Phone: [phone], Fax: [phone]: email: [email protected]
Mo.B. 1390
DIFFERENCES IN BODY COMPOSITION BETWEEN WOMEN AND MEN: IMPACT
OF HIV AND SUBSTANCE USE
Rahavan. Subhasree S, Kotler D, Loden S, Mannheimer S, Fuentes L, Scimeca M, Sivapalan V,
El Sadr W. Division of Infectious Diseases, Harlem Hospital and Columbia University, New
York, N.Y
Objective To determine body composition differences among HIV+ women and men
receiving HIVPrirr ary care.
Methods: 125 HIV + persons (65 men (HIV M) and 60 women (HIV W)) with various
stages of HIV and 64 HIV controls (29 men (CON M) and 35 women (CON W)) were
recruited. More than 95% of themr has current or past history of drug use. Measurements
include, body composition (by bioelectrical impedance analyzer RJL 10 I Q), height, and
weight (WT). Substance abuse, demographic and socioeconomic data were also collected.
Body fat (BF), body cell mass (BCM), total body water (TBW), extra cellular (ECW) and
intra cellular (ICW) water were generated using Fluid & Nutrition 3. I software. Body mass
Index (BMI, wt in kg / ht2) and body cell mass (BCM in kg)/ht in meters were calculated.
ANOVA and t-test were used to determine the differences.
Results:

N AGE WT BMI
lbs %wt
HIV M 65 43.6 153* 22.7
CON M 29 43.5 165 24.3
HIV W 60 40.9 i 37* 23.3*
CON W 35 40.1 154 27.0
SSignificantly different than the control mean.

BCM/HT
kg/m
15.9
16.3
11.9
12.1

FAT
%wt
15.2*
18.1
28.7*
37.0

TBW
%wt
6 1.3*
59.0
54.1
48.7

FFM
%wt
84.2
81.9
71.2
63.0

BCM
%wt
40.7*
39.0
32.2*
28.6

Conclusion: HIV + women and men had significantly lower mean WT fat and bcm/ht than
controls, however HIV + women also had significantly lower BMI than controls.The significant
loss of BF is higher in HIV+women than in HIV+men, which may be due to physiological and
hormonal differences. Comparison of bcm/ht, fat and BMI of our HIV+ and control men indicate that body cell mass/ht in our patients is much lower than in other black men.This may
reflect the preexisting rmalnutrition induced by long-term substance use, concomitant infections resultng fromn substance use and lower socioeconomic factors. Future studies differentiating body composition changes due to substance use from HIV infection are recommended.
Subhasree Raghavan PhD, Divof Infectious Diseases, Harlem Hospital Center,
506 Lenox Ave, Rm 10I A, New York 10037. Ph: 212 923 5732 Fax: [phone]
email: ssr [email protected].
Mo.B. I1391
METABOLISM OF RIFABUTIN IN THE RAT
Utkin, Ilya B*, Koudriakova T*, Ilatsimrrskaya E *,Thompson T**,Vouros P**, Gerber N*. *The
Ohio State University Columbus, OH, USA; *North-Eastern University Boston, MA, USA
Objective: To study mrsetabolism of rifabutin (R), an antibiotic effective in prevention of disseminated MAC infection in AIDS- patients, in rats and incubations with rat tissue preparations.
Methods: Metabolites of R excreted in urine of Sprague Dawley rats given R i.v. or formed
in incubations of R with microsomes in the presence of an NADPH-regenerating system
were isolated by high performance liquid chromatography and analyzed by nuclear magnetic
resonance and tanrdem mass spectrometry
Results: After i.v administration of [I 4C]-R to rats at a dose of 25 mg/kg, 42 % of the dose
was excreted in unne in the form of unchanged R (17 %), ipophilic (extractable with Ichlorobutane) metabolites (23 %) and highly polar products (59 %). Maor lipophilc metabolites were identified is 25 O deacetyl-R, 27 -0 demethyl-R, 20-hydroxy-R, 3 I hydroxy-R, 32 -hydroxy R, and 2 compounds tentatively identified as R species hydroxylated in the isobutylN piperidyl moiety Two nor polar metabolites did not contain a chromophore group specfic for R and lipophic metaboltes and apparently resulted from cleavage and modification
of the sobutyl N -piperidyl part of the R molecule.The rate of R disappearance was about 5
tines higher in enterocyte mnarosomes compared with liver microsomes.The patterns of
nmetabolites formed in enterocyte and liver rnicrosomes were different.The main products of
R metabolism by enterocyte microsomes were 27/-O-demethyl-R, 20 0 hydroxy-R, and
other hydroxylated derivatives. A major metabolite of R in blood and urine, 25-O-deacetyl-R,
was formed in incubations of R with the contents of the large intestine but was not detected
in enterocyte. livern, lung and kidney microsomal incubations or tissue homogenates.
Conclusions: Our findings suggest that the metabolism of R in the rat mainly occurs in the
intestine. Enterocyte P450s involved in the biotransformation of R are different from those
of liver. A possible source of 25 -O-deacetylI-R formation is bacterial metabolism of R in the
large intestine.
I. Utkirn, 5084 Graves Hall, 333 W 10th Ave. Columbus, OH 43210, USA
Telephone: [phone], Fax [phone], e mail: [email protected]
Mo.B. 1392
CLINICAL RELEVANCE OF DEXA-DETERMINED LEAN BODY MASS IN PATIENTS
WITH AIDS WASTING.
Pierson, Richard*, Wang J, Landy H**, Breitmeyer J**, Kotler D*. *St. Luke's-Roosevelt
Hospital Center, NY, NY, * *Serro o Laboratories, Inc., Norvwell MA
Objective: To assess the utility of Dual energy X ray absorptiometry (DEXA) as an accurate mneasure of change in functionrally significant Lean Body Mass (LBM) of patients with
AIDS wasting

Methods: DEXA and dilution studies were performed concurrently in 178 HIV+ patients
exhibiting > 10% weight loss and treated with placebo (PL) or mammalian cell-derived
recombinant human growth hormone (r-hGH[m], SerostimTM, Serono Laboratories, Inc.) at
an average daily dose of 6 mg for I 2 weeks. DEXA determinations were made on either a
Hologic or Lunar densitometer and each subject was studied on the same device.To distirnguish between body cell mass and extracellular water (ECW) otherwise undetermined by
DEXA methodology body water dilution studies using bromide (NaBr for total body water
[TBW]) and a non-radioactive isotope of hydrogen (D20 for FECW) were employed.
Results: Relative to PL, the r-hGH[m]- treated group had signficant increases in both LBM
and body weight (3. I kg, p<0.001, and 1.6 kg, p=0.01 I, respectively) and i decrease in body
fat (-1.4 kg, p=0.00 I). Intracellular water (TBW-ECW) also increased significantly (.7 L,
p<0.001), correlating with the change in LBM.There was no change in the ECW ICW ratio
from basel ne, indicating that the LBM gains did not represent edema. Assessment of DEXA
determined LBM in appendicular skeletal muscle is underway. Cliniclsly, LBM correlated with
physical performance and quality of life. Biviiate analyses asugested a combined effect of rhGH[m] treatment and LBM gain on reducing the occurrence of opportunistic infection.
Conclusions: Body composition in patients with AIDS wasting can be effect vely determined
by DEXA. In response to r-hGH[m], patients with AIDS wasting have clinically relevant
changes in body compositon that appear to be associated with iproved immune function.
R. Pierson, Body Composition Unit, St. Luke's-Roosevelt Hospital Amsterdam Avenue at
I Ith St., NewYork, NY 10025 Telephone: [phone] Fax [phone]
Mo.B. 1393
DETERMINANTS OF METABOLIC RATE AND BODY COMPOSITION IN ADULTS
WITH HIV INFECTION
Roubenoff, Ronenn, Skolnik P Knox T Abad L, Hoyle S, Witgert K. Spiegelman D, Gorbach S.
Issue: Wasting of lean body mass is a major problem in HIV infection.Wasting is thought to
be related to elevated resting metabolic rate, malabsorption, and anorexia, but tne role of
immune mediators in causing cachexia remains controversial.
Methods: We examined potential immune regulators of metabolic rate and fat firee mass in
95 adults with HIV infection who were free of malabsorption or 01. 75 men and 20
women (mean [~ SD] age 37 ~ 6 y, mean CD4 count 285 ~+ 272) were studied. Resting
energy expenditure (REE) was measured by indirect calormetry Body composition was
estimated by bioelectrical impedance. Production of tumor necrosis factor (TNF) and inter
leukin-IB (IL-I) by peripheral blood mononuclear cells was determined by radiolmmunoassay after culturing cells for 24 hours. CD4 counts were measured by flow cytometry. Blood
HIV burden was measured by bDNA assay (Chiron).
Results: After adjustment for gender, a major determinant of FFM, there was a strong association between FFE (kg) and CD4 counts (p < 0.000 1). However; there was no association between CD4 count and REE. REE was strongly associated with TNF production by
stimulated PBMC (p < 0.025), after adjustment for FFM and gender Neither REE nor- FFM
was associated with viral burden or IL- I production.
Conclusion: FFM declines in parallel with CD4 counts in adults with HIV infection. REE is
influenced byTNF, but not by IL-I, viral burden or CD4 count. These data suggest that antiTNF strategies may be helpful in mitigating AIDS wasting.
Ronenn Roubenoff, MD, MHS,Tufts University 71 I Washington Street, Boston, MA 021 1 I
phone [phone]; fax [phone]; email: roubenoff(chnrc tufts edu
Mo.B. 1394
A DOUBLE BLINDED CLINICAL TRIAL TO ASSESS THE EFFECT OF
PENTOXIFYLLINE IN THE INHIBITION OF TUMOR NECROSIS FACTOR
PRODUCTION IN PATIENTS WITH AIDS.
Hermida-Escobedo EC, Rivera Le6n L, Escobedo- de la Perna J. Tudon Garces H Infectious
Diseases Hospital, Mexican Institute of the Social Securty (IMSS)
Elevated levels of tumor necrosis factorm m (TNF) have been reported in AIDS patients.TNF
reverses the therapeutic efficacy of zidovudine and may contribute to the wasting syndrome. Pentoxifylline decreasesTNF production and HIV I repication in tissue culture.To
assess the effect of Pentoxifylline on tumor necrosis factor production,. weight loss, and in
the number of CD 4+ lymphocytes, a double blinded clinical trial was developed.
Materials and Methods: Forty adult patients with AIDS were included in the study Those
patients with hepatitis or any clotting abnormality were not included in the study All
patients were randomly assigned to receive either oral pentoxifyllne (400 my three times
daily for 4 weeks) or placebo (same presentation and dose).TNF, CD- 4+, CD 8+, albumin
and weight, were measured at the beginning and at the end of the four week period of the
study Adverse reactions were evaluated by the World Health Organzation crtenra.
ANOVA for two factor experiments with a repeated measure on one factor was used to
assess the change over time of each variable (i.e.TNF, CD4+), t and circular statistic were
used for a more direct visible interpretation on TNF and weht (or CD4+) chanes.
Results: Twenty one patients were assigned to the placebo group, and 19 to the expernmental group. One patient of the placebo group died before the end of the study The ratio
male:female was 3:.The mean age was 33.7 years old.The mean in itia aues of TNF in the
experimental (6.84 pg/ml) and in the control (6.53 pg/ml) groups were simlar However
there was a significant reduction (F 15.04; pc0.001) of the mean alues in the
Pentoxifylline group (4.18 pg/ml), when compared to the placebo group (8.28 eg/m).There
was a significant weight loss in the experimental grouo, whereas the placebo group showed
no weight reduction (F-6.3; p<0.05).The mean vector direction on the changes over tme
in TNF and weight, was also significant (t-7.3; pC0.000 ).
Discussion. Pentoxifylline inhibits TNF production, but it has no effect on weight loss in
AIDS patents.There is still a debate whether this drug has any chnical utslity sn AIDS wast
sng syndrome, and needs further research.
Carlos Hermida-Escobedo, MD 905 I C Siempre Viva Rd. Suit No 49 468 San Dieyo, CA.
92173-3628.Tel 52(5)343-I379;Fax [phone]

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