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

12th World AIDS Conference

Abstracts 32174-32177 555

1996 to patients seen prior to the use of combination therapies and to healthy
controls.
Methods: Body composition studies included weight, height, body cell mass
(BCM) by whole body counting of 40K, fat by dual X ray absorptiometry (DXA),
and anthropometric analyses of body fat distribution (waist/hip ratio). Seventy
eight subjects studied since January 1996 (new HIV) were matched by sex,
race, age, and height to HIV+ subjects studied before 1/96 (old HIV) and normal
controls (control). Since WHR varies proportionally with body fat, the data were
standardized by fat%.
Results: New HIV weighed more than old (p = 0.025) but less than controls (p
0.001). New HIV had more BCM (p < 0.005), but not fat, than old HIV, while
BCM and fat were both less than control (p < 0.001). WHR/fat% were higher in
both old and new HIV than controls (p - 0.001).

Weight (kg)
Old HIV men 63.6 1 12.3
New HIV men 68.7 I 9.5
Control men 82.0 12.8

Body cell mass (kg)
26.3: 5.4
28.9 1 3.9
32.6 1 4.1

Fat (kg)
13.1 + 7.7
13.6 t 7.6
22.6 + 7.3

WHR/fat%
0.104 1 0.059
0.091 ~ 0.050
0.049 i 0.029

Conclusions: In addition to losses of weight, BCM and fat, alterations in body
fat distribution are a characteristic feature in HIV infection. The occurrence of
increased abdominal fat content preceded the era of combination antiretroviral
therapy. The results were similar in men and in women and in subjects taking or
not taking protease inhibitors.
32174 Hypogonadism and wasting in the era of HAART in
HIV-infected patients
Daniel Berger', N. Muurahainen2, H. Witterti, G. Bucher1, B.E. Baker1,
J.P. Balser3. 1Center for Special Immunology, Chicago, IL; 2Serono
Laboratories, Norwell, MA; 3Veristat, Holliston, MA, USA
Objective: To determine the frequency of hypogonadism and its' relationship to
wasting syndrome and weight loss in HIV-infected men after protease inhibitors
(PIs) became widely available.
Methods: Charts of patients (pts) (98% homosexual, mean age = 37 yrs, r =
21-54) in an urban US practice (1/25/96-12/18/97) were reviewed. 127 men had
total (T) and free testosterone (FT) levels drawn. 53.5% were not on any hormonal
or wasting therapy. For at least one month prior to T and FT measurement, 55.2%
were on triple or quadruple antiretroviral (AR) therapy, 30.7% on single or dual,
and 14.2% were on no ARs. Mean CD4 count was 411 cells/mm3 and HIV RNA
was 35,500 copies/ml; 39.5% had <500 copies/ml.
Results: T levels ranged from 33-2830 ng/dl, (mean 576 ~ 433) and 16.5%
had T levels below the lower limit of normal (194 ng/dl). FT levels ranged from
14-1509 pg/ml, (mean 154 1 193) and 10.6% had FT levels below lower limit of
normal (34 pg/ml). 22/127 (17.3%) were hypogonadal defined as either T or FT
below lower normal limit; of these, 7/22 hypogonadal pts (31.8%) were receiving
testosterone increasing agents (at time of testosterone measurements). Body
mass indices (BMI) ranged from 18.7-35.3 (mean 24.7 ~ 3.0) kg/m2 with 19.5%
(22/113) having a BMI - 22kg/m2. In 2 years prior to study, 24/127 pts (18.9%) had
a diagnosis of AIDS wasting and 81/127 (63.8%) were previously diagnosed with
hypogonadism. Only 6/24 pts with wasting (25.0%) and 3/22 with BMI <22kg/m2
(13.6%) were hypogonadal. There were no significant associations between AR
therapy (triple/quad, dual, or none), CD4 counts, HIV-I RNA levels and T, FT
values. Hypogonadism was not significantly associated with wasting, low BMI or
weight loss.
Conclusions: Hypogonadism, measured by low T and FT values in this study,
appears less prevalent than reported in earlier studies and in pt charts from before
the widespread use of PIs. Hypogonadism did not correlate with CD4 count or HIV
RNA levels and was not significantly associated with wasting. In fact, 75% of pts
with wasting were not hypogonadal. Moreover, hypogonadism did not significantly
predict the occurrence of wasting.
S32175 HIV infection affects the expression of
fructose-6-phosphate,
2-kinase/fructose-2,6-bisphosphatase
Masashi Fukasawat, A. Okumura1, N. Shinomiya1, M. Rokutandat,
R. Sakakibara2. 'National Defense Medical College, Namiki 3-2 Tokorozawa,
Saitama; 2Nagasaki University, Nagasaki, Japan
Objective: To assess the influence of HIV infection on the glycolysis, especially
on the expression of a key regulatory enzyme of glycolysis in host cells.
Methods: The cDNA encoding an novel isozyme of human fructose-6-phosphate, 2-kinase/fructose-2,6-bisphosphatase kinase/Fru-2,6BPase)
which is remarkably expressed in placenta, primary lymphocytes and monocytes/macrophages and their cell lines was molecularly cloned and designated
as HP2K. We designed a specific PCR-primer set (HP-amp) for this isozyme,
and then subjected the HIV- infected and uninfected cells to the semi-quantitative
RT-PCR assay by using HP-amp and GAPDH primers as the internal control.
The recombinant HIV carrying GFP instead of nef was used for monitoring and
estimation of infectivity.
Results: The designed primer set (HP-amp) could specifically amplify HP2K
mRNA. The semi-quantitative RT-PCR assay indicated that the amount of HP2K
mRNA in HIV-infected T-cell lines (H9 and SupT1) decreased to less than 70%
of that in uninfected cells, although the splicing pattern of HP2K was not affected
by HIV infection.

Conclusion: The semi-quantitative RT-PCR assay for human placental
Fru-6-P,2-kinase/Fru-2,6 BPase suggests one of possibility that HIV infection
disorders the glucose metabolism via repressive effect of transcription of the key
enzyme for glycolysis.
32176 Long-term effects of androgen administration in men
with AIDS wasting
Steven K. Grinspoon1, C. Corcoran2, E. Anderson2, D. Schoenfeld2,
N. Basgoz2, A. Klibanski2. t Neuroendo Crine-Mass. General Hospital, Boston,
MA 02114-2696; 2Massachusetts General Hospital, Boston, MA, USA
Background: The development of successful anabolic strategies to reverse loss
of lean body mass is of critical importance in men with the AIDS wasting syndrome
(AWS). Androgen deficiency occurs in over half of all men with advanced HIV
disease and may contribute to the wasting syndrome.
Objective: To investigate the effects of physiologic testosterone administration
on body composition and quality of life in androgen deficient men with AIDS
wasting.
Methods: Randomized, placebo-controlled, double-blinded study of testosterone enanthate (TE) 300 mg or placebo IM every 3 weeks for 6 months followed
by open label administration for 6 additional months in HIV-positive men with
wasting [weight <90% of ideal body weight (IBW) or weight loss >10% of baseline and decreased free testosterone]. Lean body mass (LBM) was assessed
by dual energy absorptiometry. Secondary endpoints were weight, quality of life,
CD4 count and viral load.
Results: Age 42 ~ 8 y, weight 94 ~ 2% IBW, weight loss 18 ~ 1%, CD4 count
175 ~ 30 cells/mm3 and viral load 191,000 ~ 37,000 copies were similar between
the groups at baseline. TE-treated subjects gained more LBM than placebo [2.0
i 0.7 kg (+4.2%) vs. -0.6 ~ 0.7 kg ( 0.7%), P = 0.036 (months 0-6)]. TE-treated
subjects also gained more weight, but the change did not reach significance (1.6
~ 1.3 vs. -0.2 ~ 1.3 kg). TE-treated subjects reported benefit from the treatment
(P = 0.036), feeling better (P = 0.033) and improved quality of life (P = 0.040)
vs. placebo-treated subjects. TE was well tolerated. No significant differences
in viral load or CD4 count were observed between the treatment groups. For
subjects initially randomized to placebo, the gain in LBM was significantly greater
during open label treatment (months 6-12) than placebo treatment (months 0-6)
[1.9 ~ 0.7 kg (+3.6%) vs. -0.6 ~ 0.7 kg (-0.7%), P = 0.031]. Subjects initially
randomized to TE continued to gain IBM during the open label extension period
(+3.1 ~ 1.2%, months 6-12). Subjects receiving TE for 12 months gained more
LBM than subjects receiving TE therapy for only 6 months [3.7 ~ 0.8 kg (+7.6%)
vs. 1.0 i 1.0 kg (+2.4%), P = 0.05]. A similar trend in weight was seen.
Conclusions: These data from a long-term study, demonstrate that physiologic
testosterone administration increases LBM and improves quality of life among
androgen deficient men with the AIDS wasting syndrome. The increases in LBM
are sustained for one year of therapy, indicating that such treatment should be
continued long-term. Men with the AWS should be screened for hypogonadism
and treated with physiologic testosterone administration to improve lean body
mass and quality of life.
S32177 Impact of protease inhibitor treatment on body
composition and prevalence of malnutrition in HIV
positive outpatients
Achim Schwenk, A. Beijenherz, G. Kremer, H. Steuck, B. Salzberger, V. Dielh,
G. Faetkenheuer. Klinik 1 Fuer Innere Medizin, Universitaet Koeln (Cologne).
Koeln, Germany
Objectives: To assess (1) the prevalence of malnutrition, and (2) changes in
body composition in HIV infected outpatients before and after widespread use of
protease inhibitor (PI) treatment.
Patients and Methods: Bioelectrical impedance analysis (BIA) was performed
twice in all HIV-positive outpatients at a tertiary care clinic, 500 days apart (T1 =
march/april 96, T2 = july/august 97). PI were prescribed to 17/247 patients at T1,
and to 169/266 patients at T2. Patients assessed at T1 and T2 and treated with
PI (n = 112) were followed longitudinally, including monthly weight assessment.
Results: Prevalence of malnutrition decreased from 1996 to 1997 following
several definitions: Body mass index was below 19 kg/m2 in 13.4% vs. 6.0"'.
Loss >5% of usual body weight was documented in 43.3% vs. 28.9%t. Weight
loss in the subsequent month >2% occurred in 24.4% vs. 14.4%. Phase angle
(BIA) was <5 in 19.0% vs. 7.5% t. Some of this change in prevalence is due to
demografic changes in the population attending the clinic. For example, in 1996
a phase angle <5% was found in 28.6% of patients only seen at T1 but in 11.1%
of patients followed until T2. In 1996, this percentage was 6.9% (T2 only) and
8.1% (followed from T1).
In patients followed longitudinally during PI treatment, weight gain from T1 to
T2 was not significant (+0.9 ~ 5.2 kg, p = 0.07) but body cell mass increased
by 3.3 ~ 2.6 kg:, Extracellular mass increased by 1.2 ~ 1.8 kg:, and body fat
decreased by 3.6 ~ 4.1 kg:. Body composition changes were not correlated to
suppression of viral load or CD4 cell increase. (: p < 0.05,: p < 0.01, t: p <

0.001, $: p < 0.0001)
Conclusion: In the first era of protease inhibitor treatment, the prevalence of
malnutrition in HIV positive outpatients was markedly reduced. Body composition
improved in patients receiving protease inhibitors, with an increase in body cell
mass and decrease in body fat. Virological and immunological markers of treatment success cannot fully explain these changes. Indirect treatment effects, such
as increased physical activity, may be involved.