Abstract Book Vol. 2 [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

XIV International AIDS Conference

Abstracts ThPeB7321-ThPeB7325 415

Presenting author: Elke Lauenroth-Mai, Turmstr.76A, 10551 Berlin, Germany,
Tel.: [phone], Fax: [phone], E-mail: [email protected]
ThPeB7321 I Lipoprotein patterns associated with antiretroviral
therapy indicate a low cardiovascular risk
S. Mauss', J. Stechel2, G. Schmutz1, F. Berger', W.O. Richter3. 1 Center for HIV
and Hepatogastroenterology, Duesseldorf, Germany; 2Private Practice, Cologne,
Germany; 3Research Institute for Lipid Metabolism, Windach, Germany
Background: Hypercholesterolemia associated with antiretroviral treatment
(ART) led to concerns about an increased cardiovascular risk in HIV+ patients
(pts). To estimate this risk we compared the lipoprotein particles of HIV+ pts with
ART with pts with familial combined hyperlipidemia (FCH) (high cardiovascular
risk) or familial hypertriglyceridemia (FHT) (low cardiovascular risk).
Methods: Fasting serum samples were drawn from consecutive pts with HIV, FHT
and FCH. Total cholesterol, LDL-, HDL-cholesterol, triglycerides, apolipoprotein
Al and B were determined in serum. VLDL were prepared by ultracentrifugation
and analyzed for cholesterol, triglyceride and apo B.
Results: Hypercholesterolemia (>200 mg/dl) was found in 85/187 HIV+ pts
(45%). Of these 14% had an elevated LDL-cholesterol (Fredrickson type 2a),
16% high LDL- and VLDL-cholesterol (Fredrickson type 2b), 66% had an elevation of VLDL-cholesterol (Fredrickson type 4) and 4% high HDL-cholesterol. HDLcholesterol in HIV+ pts is generally lower than in the normal population. However
compared to pts with FCH or FHT, HIV+ pts had higher HDL-levels (p<0.05).
VLDL composition was analysed in 34 HIV+ pts with Fredrickson type 4. The ratio of VLDL-triglycerides to VLDL-apo B was 16.26~.0. This ratio was not different
from 14 pts with FHT (16.9~6.0, p=0.27), but did not overlap with the results from
10 pts with FCH (6,8+1.0, p<0.0001).
Conclusions: The analysis of the VLDL-composition in HIV+ patients with
Fredrickson type 4 hyperlipidemia revealed the presence of large VLDL-particles
with no increase in number. This pattern resembles FHT. It is different from FCH,
where an increase in number of normally sized VLDL-particles occurs. In addition
HDL-cholesterol was higher in HIV+ pts than in both HIV- groups. This indicates
that the large subgroup of HIV+ patients under ART with hypercholesterolemia
due to VLDL-cholesterol may have a lower cardiovascular risk than generally expected.
Presenting author: Stefan Mauss, Grafenberger Allee 128a, 40237 Duesseldorf, Germany, Germany, Tel.: [phone], Fax: [phone], E-mail:
maussst @ compuserve.com
ThPeB7322 A randomised open label study of 3 substitution
strategies in hypercholesterolemic persons
virologically controlled on first line antiretroviral
therapy (ART)
G.J. Moyle, C. Baldwin, B.G. Gazzard. Chelsea and Westminster Hospital,
London, United Kingdom
Introduction: Clinical data support a role for PIs in metabolic and morphological
changes in persons on ART Additionally, efavirenz (EFV) may lead to cholesterol
elevations in some individuals. Cohort studies have suggested that morphological changes may occur more commonly on d4T-based regimens and lipids may
improve after d4T replacement (St Marc et al. AIDS 1999).
Methods: 30 patients on d4T-based first therapy with cholesterol > 180mg/dI and
viral load <50cps/ml were randomised to either replace d4T with abacavir (ABC)
(group A), PI/EFV with ABC (B) or d4T and PI/EFV with ABC+AZT (C). Patients
were assessed with fasting bloods and DEXA scan at baseline and 12 weekly to
week 24.
Results: All patients remained <50cps/ml. One patient discontinued due to ABC
hypersensitivity, 2 patients withdrew for personal reasons before week 12. DEXA
scan data indicated no difference between the groups with regard to fat mass:
arm fat fell 10-14%, leg fat was unchanged in A, rose 25% in B and fell 12.5%
in C. Truncal fat was unchanged in groups A and C but increased by 25% in B.
With regards to total cholesterol, switching from d4T to abacavir led to a rise in
total cholesterol of 22.6% whereas group B saw a 26% decline in total cholesterol
and C a 21% decline in total cholesterol (p<0.05 vs. A). This was accounted for
by LDL levels, which rose by 27% in A, fell by 26% in B and by 15% in group C.
Triglycerides rose by 14% in A, fell by 30% and 34% in B and C. Insulin levels 20%
rose in A but fell 21% in B and 43% in C (p<0.05 vs. A). No significant change in
lactate levels were observed during the study.
Conclusions: Substitution of d4T with ABC does not lead to improvements in
fasting cholesterol, triglycerides, insulin, lactate or fat mass. Replacement of
PI/EFV with ABC may lead to improvement in lipids and insulin. Abacavir substitution maintains virological control in first line therapy patients.
Presenting author: Graeme Moyle, 11 Pembroke Place, London, United Kingdom, Tel.: [phone], Fax: [phone], E-mail: [email protected].
co.uk

ThPeB7323 Zinc intake and mortality in HIV-1 infected drug
users
M.K. Baum', A. Campal, S. Lai2, H. Lai2, Z. Yang1, S. Sales1, K. King1,
B. Page 3. 'Florida International University, Miami, FL, United States; 2John
Hopkins University Baltimore, MD, United States; 3 University of Miami, Miami,
FL, United States
Background: Zinc (Zn) deficiency is associated with immune abnormalities and
increased susceptibility to infections. While Zn deficiency has been observed in
various HIV+ populations, including those on HAART, its relevance in HIV disease
is not understood. The objective of this study was to evaluate whether dietary Zn
intake is related to Zn deficiency and mortality in HIV+ drug users.
Method: Immunological, nutritional and clinical profiles of 118 HIV+ drug users
were assessed every 6 months in Miami, Florida between 1994-98. HIV-related
mortality was confirmed with data from the Medical Examiner. Zn intake was obtained by the Willet's food frequency questionnaire. The effect of dietary Zn intake
on mortality was determined by a multivariate Cox proportional hazards model
with dietary Zn and CD4 cell count as time-dependent covariates.
Results: HIV-related death occurred in 22 individuals during the course of the
study. Mean intake of Zn (10.1 mg/day~5.5) was below the recommendations
for healthy US population (RDA is 15 mg/day for men, 12 mg/day for women).
Zn deficiency (plasma Zn<0.751Lg/ml), was present in 56% (N=67), 7 of whom
died during the follow-up period. Dietary Zn intake below the median of 9.34
mg/day dramatically increased risk for HIV related mortality (RH=36.9,p<0.03).
When dietary Zn intake was treated as a continuous variable, a dose-response
relationship between dietary Zn and mortality was found. The risk of dying from
HIV-related disease decreased by 33% for every 1 mg/day increase in dietary Zn
intake, and this relationship was independent of antiretroviral therapy, CD4 count
at baseline and over time.
Conclusions: Low dietary Zn intake is a strong independent predictor of mortality
in HIV infected drug users. Clinical trial is ongoing to determine whether increasing dietary Zn intake will reduce HIV-associated mortality in this population.
Support: NIDA, NIMH, FIC.
Presenting author: Marianna Baum, Florida International University, University
Park, CH 230, Miami, Fl. 33199, United States, Tel.: [phone], Fax: [phone], E-mail: [email protected]
ThPeB7324 Effects of HIV protease inhibitors on the
differentiation of the 3T3 442A adipocyte cell line
N. Parassoll, Z. Amri2, C. Le Saint 3, J.P. Vincent4, A. Cupo4. IStudent,
Valbonne, France; 2CR1 CNRS, Nice, France; 3PhD, Valbonne, France; 4PU,
Valbonne, France
The cellular metabolism of the antiretroviral drugs may contribute to reduce the
efficient cellular concentration of drugs able to contain the viral load. High therapeutic regimen, used to overcome clinical failures, induce dramatic side effects
among them dramatic metabolism defects named lipodystrophy syndrome. This
syndrome is associated with hyperinsulinaemia, insulin resistance and especially
with hyperlipidaemia which increase significantly cardiovascular risks.
The effects of Nelfinavir and Indinavir on the proliferation and the differentiation
by hormonal impregnation were studied on the 3T3 442A cell line and compared
to the control 3T3 C2 cell line. The expression of the early and late adipocyte
differentiation markers and the transcription factors (PPAR gamma, CEBP alpha
and beta, aP2) will be studied by northern blots in order to determine the cellular
targets of the antiretroviral drugs.
We observed that Nelfinavir inhibited the proliferation and the differentiation of
adipocytes. In opposition, Indinavir did not have any effects. A broad intracellular
accumulation of Nelfinavir was observed at the adipoblaste and the preadipocyte
stage. The strong inhibition of aP2 in adipocytes, correlated with the high intracellular concentration of protease inhibitor, might accounted for the lipoatrophic
effects of Nelfinavir.
Presenting author: Anny Cupo, Institut de Pharmacologie Moleculaire et Cellulaire CNRS-UMR 6097, 660 route des Lucioles, 6560, Valbonne, France, Tel.:
[phone], Fax: [phone], E-mail: [email protected]
ThPeB7325 Lipid Profile of untreated HIV positive men who
have sex with men
B. Baza Caraciolo1, J. Sanchez Alonso2, D. Carrio Montiel1, S. del Corral del
Campo', A. Quintana Molina', M. Heredero Sebastian2, S. Garcia Pbrez',
J. del Romero Guerrero1. 'Centro Sanitario Sandoval, Servicio Madrilefo de
Salud, Centro Sanitario Sandoval, C/Sandoval, 7, 28010-Madrid, Spain;
2Laboratorio Duque de Ahumada, Madrid, Spain
Background: Altered lipid metabolism is known to affect immune processes.
Most of studies are refered to aids patients and few of them have investigated

the relationship between serum lipid levels and CD4 lymphocytes (CD4) or viral
load (VL). This study characterized the lipid profile of asymptomatic untreated
HIV positive (+) individuals comparing it with a control group.
Methods: 35 asymptomatic untreated HIV (+) men who have sex with men
(MSM), 32.7 ~ 6.6 years. They were classified into groups according to CD4 and
VL. As control group 39 HIV negative (-) MSM, 32.8 + 8.5 years. Biochemistry
parameters: total cholesterol (CH), triglycerides (TG), HDL-cholesterol (HDL-c),
LDL-cholesterol (LDL-c), albumina (ALB), alanine-amino- transferase (ALT) were