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

556 Abstracts 32178-32181

12th World AIDS Conference

32178 The key role of stress hormones during paediatic HIV
infection: Three years of follow-up
Mariangela Rondanelli1, D. Caselli2, A. Maccabruni3, M. Maghnie2,
L. Bacchella4, A. De Stefano4, E. Ferrari1. Department of Internal Medicine and
Medical Therapy Chair of Geriatrics University of Pavia; 2Pediatric Department
I.R.C.C.S. Pol San Mateo 27100, Pavia; 3Dept. Infect. Diseases I.R.C.C.S. Pol
San Mateo 27100, Pavia 4Nuclear Medicine Dept. I.R.C.C.S.S. Maugeri
"Foundation 27100, Pavia, Italy
Background: Disturbances of growth and development in children with HIV infection are now well recognised; in order to better understand these alterations
in growth process, it is important to account for the role of stress hormones,
such as GH, cortisol, FT3 and glucagon. Given this background, we start on
a perspective study in order to evaluate these stress hormones in a group of
HIV-infected children. Nowadays we are arriving at the third year of follow-up.
Moreover, the HIV-infected patients were submitted to glucagon test because this
test gives valid esitimates of residual pancreas f cell function.
Methods: 15 HIV-infected children (8 males and 7 females, ranging in age
from 2 to 14 year) without active opportunistic infection (9 paucisymptomatic
and 6 symptomatic) were evaluated.. No patients receives drugs toxic for the
pancreas and serum amylase and lipase levels were normal. Thirteen healthy
children matched for age and sex were chosen as control group. Nine patients
were submitted to glucagon test (0.1 mg/Kg i.m.); blood samples were collected
at 0, 15, 30, 45, 60 minutes to assay insulin and glycaemia. The serum levels of
hormones were measured by RIA.
Results: At all evaluations the mean levels of serum GH, cortisol and FT3
were similar among patients and controls, while in HIV-infected children the
glucagon levels were markedly elevated in comparison to controls (p < 0.001).
The glucagon test gave a normal glycaemic curve in 6 patients; glycaemic responses to glucagon stimulation was significantly impaired (<50%) in 3 patients.
As regard the insulinemic response, 3 patients exhibited an exaggerated insulin
response (>80 mU/L). At last, we found that the increased serum levels of
glucagon was significantly associated with poor statural growth and decreased
weight gain.
Conclusion: The results showed an important rised in glucagon secretion. This
increased glucagon secretion may play a key contribute to the statural and ponderal growth alterations seen in HIV-infected children, as shown by the correlation
between the glucagon levels and the poor statural growth and decreased weight
gain. Thus, the hyperglucagonemia may be one of the the potential mediators of
the HIV-related catabolic state.
32179 Growth hormone produces striking anabolic effects in an
HIV-infected adolescent with failure-to-thrive and wasting
Mitchell E. Geffner, D. Dreimane, K. Nielsen, P. Krogstad, E.R. Stiehm,
Y.J. Bryson. UCLA Children's Hospital 10833 Le Conte Ave/MDCC 22-315 Los
Angeles CA 90095, USA
Objective: To demonstrate the efficacy and safety of recombinant human growth
hormone (rhGH) in the treatment of failure-to-thrive (FTT) and wasting in a
15-yr-old male with HIV infection acquired by transfusion shortly after birth.
Design: Prospective case report.
Methods: rhGH therapy (Serostim", Serono Laboratories, Norwell, MA) at 3
mg/day (extrapolated from doses approved for adult HIV wasting) (along with
Ritonavir') was administered for one year. Clinical, psychological, and laboratory
parameters were followed quarterly to determine efficacy and safety.
Results: Despite standard retroviral therapy, this boy gained only 3.0 kg and
grew only 9.5 cm in 6.5 yr before starting rhGH. He had striking wasting of his
facial muscles, no evidence of puberty, and complained of easy fatigability, poor
appetite, slow hair growth, and mild depression. At 13.9 yr, his GH levels were
low and, at age 15 yr, his IGF-1 was 14 ng/mL (N = 180-836), IGFBP-3 1.2
mg/L (N = 2.0-5.9), and bone age 11 yr. Prior to starting rhGH, his ht was 127.9
cm (SDS -5.10) and wt 23.2 kg (SDS -4.00). After 12 mo, his ht increased
by 10.9 cm (ht SDS -4.81) and wt by 12.0 kg (wt SDS -3.09). In addition, his
muscle wasting markedly improved and he noted increased energy and appetite,
a happier disposition, and rapid hair growth. His IGF-1 and IGFBP-3 peaked at
459 ng/mL and 4.5 mg/L, respectively. His alkaline phosphatase increased from
192 to 641 U/L and his fasting cholesterol increased from 108 to 446 mg/dL
(thought to be related to Ritonavir"). Concomitantly, his CD4 count increased
from 8 to 558 cell/mm3 (1 to 19%) with no significant change in his CD8 count,
QUIGs, or plasma HIV-PCR.
Conclusion: Pharmacological doses of rhGH given for 1 yr to an adolescent
male with perinatally-acquired HIV infection, clear-cut FTT, and wasting for at least
6.5 yr, resulted in striking anabolic effects with possible immunological benefit on
CD4 cells, and no serious toxicity.

32180 j Change in loglo HIV RNA and protease inhibitor use
associated with weight change in HIV+ men in a national
clinical trial
Subhasree Raghavan', Lisa B. Grant3, Glenn Barisch3, Melanie Thompson4
Bruce Williams5, Noe Matoe6, Wafaa M. EI-Sadr2. 1Columbia University, 900
West 190th Street #15B, New York 10040; 2Columbia University Harlem
Hospital, New York 10032, NY; 3University of Minnesota, Minneapolis, MN;
4 Community Consortium of Atlanta, Atlanta; 5 University of New Mexico,
Albuquerque, NM; 6Henry Ford Hospital, Detroit, Ml, USA
Objective: To determine the associations between change in HIV RNA (Chiron
bDNA assay), Protease Inhibitor (PI) use and change in weight (wt) among HIV+
males with CD4 < 300.
Methods: Stepwise multiple regression models were used to analyze the data
on 262 men from CPCRA 036 at baseline, 4 months, and 8 months. The study
period include 9/95-5/97.
Results: African American (26%), Latino/Hispanic (6%), White (66%); mean
age in yrs (40) & history of IV drug use (16%). Base Line (BL) antiretroviral use
(92%) & BL PI use (16%). History of progression of opportunistic diseases (POD)
(31%), mean BL CD4 (165 cells/mm3), mean BL logio RNA (1.8), mean BL wt.
(76 kg), mean Kamofsky score (90). Percent POD during follow-up (4 mo., 5.0%)
(8 mo., 6.9%), mean percent change in CD4 (4 mo., 66%) (8 mo., 96%), mean
change in loglo HIV RNA (4 mo., -0.3) (8 mo., -0.7), mean percent change in
wt. (4 mo., 0.14%) (8 mo., 0.05%).
Change in HIV RNA at eight months [logio (follow-up/baseline)]
<-1 -1 to -0.5 -0.5 to 0 0 to 0.5 0.5to 1 1
N 85 44 76 40 13 4
Ave. % Wt. Change 1.18 0.68 -0.40 -2.33 1.20 -2.00
Protease inhibitor use (BL/8-month follow-up)
Yes/No No/No Yes/Yes No/Yes
N 4 110 39 109
Ave. % Wt. Change (SE) -6.12 (3.63) -0.57 (0.52) -0.95 (0.93) 1.26 (0.64)
Multiple regression analyses indicate that 4-month wt. change is negatively
associated with BL wt. (P < 0.05). 8-month wt. change is negatively associated
with BL wt. (P < 0.05), change in loglo RNA (P < 0.05), POD during follow-up (P
< 0.10) & BL PI use (P < 0.05) and is positively associated with initiating PI (P <
0.10). Neither BL CD4 or percent change in CD4 during follow-up appear to be
associated with % wt. change
Conclusion: Viral suppression over eight month period was associated with
positive changes in weight, where as increase in HIV-RNA levels were accompanied by negative changes in weight. These finding suggest some degree
of immunological recovery following suppression of HIV replication resulting in
reduction of HIV-associated weight loss. PI initiation was also associated with
weight gain, however long term use of protease inhibitors failed to show such an
association which needs further investigation.
S32181 Altered body fat distribution in HIV infection: Regional
body composition measurements by whole body MRI and
DXA scans
Ellen S. Engelson, D.P. Kotler, Y.X. Tan, D. Agin, B. Bashist, J. Wang,
S.B. Heymsfield. St. Luke's-Roosevelt Hospital Center, New York, NY USA
Background: Recent observations have documented the development of truncal obesity in HIV-infected men receiving combination antiretroviral therapy. We
prospectively examined regional body composition using whole body Magnetic
Resonance Imaging (MRI) and whole body Dual Energy X-ray Absorptiometry
(DXA) scans in HIV-infected men and women and matched controls.
Methods: Twenty-one HIV-infected people (13 men and 8 women) were
matched with healthy controls by sex, race, age (A 5 years) and height (4
10 cm). Five male and 3 female HIV+ subjects reported increased abdominal
girth, with or without weight gain. Total body skeletal muscle, subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and total adipose tissue (TAT)
volumes were determined by MRI, and arm, leg, and truncal fat-free and fat mass
were determined by DXA. T-tests were performed to compare HIV+ to control,
and to compare HIV+ with vs without truncal obesity, as defined by history.
Results: Body mass index (kg/m2), and fat and fat-free mass contents by DXA
were similar in HIV+ and controls. SAT values were lower in HIV+ (p = 0.044)
while VAT contents were similar. Among HIV+ subjects, those with truncal obesity
were older (p < 0.002) and had higher BMIs (p = 0.014), truncal fat (p < 0.001),
VAT (p < 0.001), TAT (p < 0.003), and VAT/TAT (p = 0.017), but similar total
and regional fat-free mass, total body skeletal muscle, and SAT. Three subjects
with truncal obesity were not taking protease inhibitors, and one was taking no
antiretroviral medication.
Conclusions: There is a redistribution of body fat in some HIV-infected people,
with decreased peripheral and increased central fat, which is visceral and not

subcutaneous in location. The changes occur in women and men, and are not
limited to patients receiving protease inhibitors.