Bridging the Gap: Conference Record [Abstract book, International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

12th World AIDS Conference

Abstracts 32164-32168 553

I32164 Treatment of dorsocervical fat pads and truncal adiposity
with serostim (recombinant human growt hormone] in
patients with AIDS maintained on HAART
Ramon Torres. St. Vincents Hospital and Medical Center, 412 Sixth Avenue
Suite #401, New York, NY 10011, USA
Introduction: Dorsocervical fat pad enlargement (buffalo hump) associated with
truncal obesity and peripheral lipodystrophy and hypertriglyceridemia, often associated with lean body mass wasting has been described in HIV positive patients
maintained on highly active antiretroviral therapy (HAART) including protease
inhibitors. The pathogenesis of this disorder is unknown, although dysregulation
of fat metabolism is suspected. No treatment other than surgical lipo-suction of
the fat pad has been shown to be effective. Recombinant human growth hormone (rhGH) [Serostim] is known to promote fat catabolism and lean body mass
anabolism, reversing wasting and the futile cycling of fatty acids in AIDS.
Methods: Two AIDS patients (a male and a female) with a history of long term
use of HAART, including protease inhibitors (saquinavir and indinavir in one and
ritonavir, saquinavir, and nelfinavir in the other) developed buffalo humps, central
adiposity and peripheral muscle wasting, associated with fatigue and hypertriglyceridemia (serum triglycerides 400-2000). One patient also had mild hypercholesterolemia (serum cholesterol 200-350). Baseline bioelectric impedance analysis,
(BIA) in one patient revealed increased body fat and low borderline lean body
mass. Therapy with rhGH [Serostim] was initiated in both patients at a dose of 6
mg/day subcutaneously for 12-24 weeks.
Results: After 12 weeks of Serostim therapy the female patient had total
resolution of the buffalo hump, decreased truncal obesity, increased energy and
improved muscle strength. After 6 weeks of Serostim therapy the male patient had
a notable 50% regression of the buffalo hump, and increased muscle strength.
Weight did not change significantly in either patient, yet cholesterol and triglyceride levels decreased, but remained above the limit of normal for both patients.
Both patients remain on therapy and are being followed with serial BIAs. Adverse
effects include mild joint pain in one patient and mild hypertension and elevation
of pancreatic enzymes in the other.
Conclusion: rhGH [Serostim] may be an effective treatment for the abnormal
truncal adiposity and dorsocervical fat pads associated with HAART use in AIDS
patients, and deserves further investigation.
32165 Tumor necrosis factor response to megestrol acetate
therapy in AIDS-associated wasting
Francisco Arnalich1, P.L. Martinez-Hernandez1, A. Hernanz2, C. Montiel3,
J. Camacho1, C. Fernandez-Capitan', J. Gonzalez-Garcia'. 'AIDS Care Unit,
2Clinical Biochemistry Service - Hospital Universitario "La Paz", Edifico H.
Maternidad Planta 8, Madrid; 3Department of Pharmacology, Facultated de
Medicina, Universidad Autonoma, Madrid, Spain
Background: Recent trials of patients with AIDS and cachexia showed that megestrol acetate (MA) can increase appetite and body weight by as yet unknown
mechanisms.
Objective: to evaluate the effects of MA therapy on the circulating levels
of some appetite regulators in patients with AIDS-wasting, and whether these
changes translated into an increase in weight gain.
Design: Randomized, placebo-controlled, double-blind, crossover trial.
Patients: Eighteen AIDS patients without concomitant diseases who received
stable doses of antiretroviral drugs and had >10% loss of usual body weight were
randomized to receive MA (480 mg daily) and placebo for 8 weeks, followed by
a 4 week washout period and then crossed to receive the alternate treatment for
the next 8 weeks.
Main Outcome Measures: Body weight and total muscle mass assessed by
anthropometry, self-report of appetite, plasma and cerebrospinal fluid (CSF) concentrations of /f-endorphin, cholecystokinin (CCK-8s), TNF-a and their soluble
receptors. Values were compared across treatment arms and with the baseline
values within treatment arms by a two-way analysis of variance with repeated
measures according to the method for crossover trials.
Results: Treatment with MA resulted in weight gain (mean changes from baseline ~SD, 5.62 ~ 0.52 kg; p < 0.001) and trends toward increased total muscle
mass (1.2 ~ 0.38 kg, p = 0.057), accompanied by a decrease in plasma levels
of TNF-u (-5.04 ~ 0.92 pg/ml, p = 0.0479) and in plasma and CSF levels of
sTNFR-p55 (-1.48 + 0.07, and -0.33 + 0.02 ng/mL, respectively, p < 0.001 for
both variables). Plasma and CSF concentrations of i/-endorphin and CCK-8s did
not change significantly from baseline.
Conclusions: the MA effect in promoting weight gain in AIDS-wasting might
be mediated through an inhibition of the TNF-a, system activity.
32166 Effect of a high protein diet upon protein metabolism in
HIV-infected men and women
Ellen S. Engelson1, D.P. Kotler1, I. Schur1, D.E. Matthews2. 1St.
Luke's-Roosevelt Hosp Center S&R1301 421 W113 St. New York, NY 10025;

2University of Vermont, USA
Background: Current treatments for HIV-associated malnutrition have many limitations, including lack of muscle repletion, high cost and undesirable side effects.
High protein diets might promote positive nitrogen balance and muscle repletion
without undesirable side effects. Our objective was to compare the effects of
isocaloric protein and carbohydrate supplements in HIV-infected and uninfected
men and women.

Methods: This was a 10 day inpatient study with a prospective, double-blind,
placebo-controqlj, randomized crossover design. Subjects were 6 clinically stable HIV-infecte'individuals with history of weight loss and body cell mass less
than 90% of gender-, race- and height-adjusted norms, and 4 healthy controls.
Subjects consumed a liquid formula (35 kcal/kg and 1.2 g protein/kg daily) plus
2.4 g/kg.day-1 of either maltodextrin carbohydrate or cow's milk whey protein for
5 days each. Measurements included body composition by DEXA, and protein
metabolism by stable leucine isotope infusion with plasma and breath isotope
analyses. Leucine results were normalized by fat free mass.
Results: (expressed as mean ~ sd; /lmoles leucine/kg FF.hour1)
Leucine Leucine Nonoxidative Leucine
Flux Fasted Oxidation disposal Flux Fed
Normal Protein Diet
Controls 127.9 22.2 17.6 L 3.4 110.3 ~ 19.8 150.8 ~ 39.8
HIV+ 1238.8 ~23.3 16.4 ~ 4.0 112.4 ~ 19.7 157.2 ~ 20.2
High Protein Diet
Controls 123.5 32.3 20.2 9.2 103.2 ~ 25.1 271.2 ~ 117.4
HIV+ 131.4 ~ 25.5 19.7 ~ 5.9 111.7 - 21.2 210.6 ~ 51.0
There were no significant differences in leucine metabolism between control
and HIV+subjects. Leucine flux in the fed state increased vs fasted an average
of 26.2 ~ 24.1 on normal protein and 106.6 ~ 71.0 on high protein (p = 0.01).
Conclusions: These results suggest that protein metabolism is not significantly
perturbed in clinically stable malnourished HIV-infected individuals. The metabolic
response to a high protein diet is not impaired and protein supplementation stimulates protein metabolism as it does in uninfected individuals. However, the ability
of a high protein diet to reverse HIV-associated malnutrition and body composition
changes remains unknown.
506*/32167 1 HIV RNA, CD4+ cell count, and immune activation
markers predict HIV-related wasting prior to AIDS
in the Multicenter AIDS Cohort Study (MACS)
Robert H. Lyles', A.M. Tang1, J.W. Mellors2, J.B. Margolick1, B.R. Visscher3,
J.P. Phair4, N.M.H. Graham5. 1Johns Hopkins School of Public Health, Room
E7007, 615 N Wolfe Street, Baltimore, MD; 2University of Pittsburgh & VA
Medical Center, Pittsburgh, PA; 3UCLA School of Medicine, Los Angeles, CA;
4Northwestern School of Medicine, Chicago, IL; 5Glaxo Wellcome Research and
Development, Research Triangle, NC, USA
Objectives: To study associations of baseline HIV RNA (bDNA version 2.0 assay
on cryopreserved plasma samples), CD4+ lymphocyte count, and serum levels of
neopterin and /2-microglobulin with subsequent weight loss among HIV-infected
individuals free of clinical AIDS.
Methods: 1588 HIV+ MACS participants comprised the study population. Outcomes were first occurrence prior to AIDS of i) self-reported unintentional loss
of >10 Ibs. or ii) documented loss of >5% of baseline weight. HIV RNA and
CD4 were each grouped into five categories, with cut points at 0.5, 3, 10, and
30 K copies/mL and at 750, 500, 350, and 200 cells/uL. Neopterin and /12-m.
were divided at their quartiles. Logrank tests and Cox regressions were used to
characterize patterns of elevated risk. Linear trajectories in weight over time and
variability about these trajectories were estimated separately for each subject.
Distributions of these variables were compared across baseline marker categories
via nonparametric tests.
Results: 721 of the 1,588 participants contributed subsequent weight loss
events. Logrank tests were significant (p < 0.001), and median slopes of weight
were heterogeneous across categories (p < 0.001) for all four markers, with
greater risk of events and steeper decline in categories indicative of more advanced HIV disease. For those in high categories of HIV RNA and low categories
of CD4, less variability about weight trajectories was observed relative to the full
study population (p < 0.001). In a single Cox regression model controlling for age
and baseline weight, after collapsing categories with similar risk, adjusted relative
hazards for the four markers (all significant, p < 0.05) were:
HIV RNA (copies/mL) CD4 (cells/uL) Neopterin (nmol/L) 12-m. (ug/L)
0.5-10 K 10-30 K >30 K 200-350 - 200 >16.14 (3rd quartile) ->2.98 (3rd quartile)
1.6 2.0 2.7 1.3 2.1 1.2 1.3
Conclusions: Baseline virologic (HIV RNA), immunologic (CD4) and immune
activation (neopterin, #/2-m.) markers all contributed prognostic information for
weight loss events in AIDS-free HIV+ MACS participants. HIV RNA and CD4
count were associated with both the rate of decline and the variability of weight.
Unlike in most studies with AIDS or death as the outcome, markers of immune
activation remained prognostic after adjusting for HIV RNA and CD4. This may
be relevant to metabolic processes involved in HIV-related wasting prior to AIDS.
[ 32168 Increased resting energy expenditure (REE) is associated
with increased plasma HIV RNA

Abby Shevitz1, D.L. Spiegelman2, J.K. French2, R. Roubenoff1, T.A. Knox3,
G.L. Gorbach1, P.R. Skolnik3. 1 Tufts University School of Medicine 136 Harris
Ave., Boston, MA 02111; 2Harvard School of Public Health Boston MA; 3New
England Medical Center Boston MA, USA
Background: Although patients lose weight in advanced HIV disease, REE has
been variably reported to be high, low, or normal. HIV RNA measurements have