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

12th World AIDS Conference

Abstracts 12319-12322 77

Methods: We evaluated ritonavir use in a prospective trial of unrestricted ARV
therapy. HIV RNA and CD4 were measured every 2 months and ARV changes
were carefully recorded. Baseline (time of change to RTV regimen) CD4, HIV
RNA, prior ARV treatments and components of the new RTV regimen were
evaluated as to the effect on change from baseline in HIV RNA (ARNA) and the
proportion of patients with HIV RNA < 400 copies/ml (UND).
Results: The mean baseline CD4 and loglo HIV RNA were 149 cells/ml and
4.53 copies/ml respectively. Subjects had a median duration of 20 months of prior
ARV and 23/79 (29%) were PI naive. The ARNA at months 2, 4 and 6 were -0.8
(n = 48), -0.9 (n = 33) and - 0.8 (n = 20). In the entire cohort, neither baseline
CD4, HIV RNA nor length of prior ARV predicted virologic response (ARNA or
% UND) while prior PI treatment (saquinavir or indinavir) and duration of prior
PI reduced ARNA and % UND at month 2 (p < 0.05). Sixty percent (9/14) of
PI naive versus 30% (10/33) PI experienced patients had UND RNA at month
2. In PI experienced patients, baseline HIV RNA > median (4.6) predicted poor
response to a new RTV regimen [9% (1/11) vs 47% (8/17) UND at month 2, p
= 0.05] In experienced patients, using dual PI in addition to changing at least
one nucleoside did not improve the % UND at month 2 [14% (2/14) vs 42%
(8/19)].
Conclusion: In these patients receiving unrestricted ARV, response to RTV
was most influenced by prior PI therapy. Baseline HIV RNA > median reduced the
% UND at month 2 in PI experienced patients and changing multiple components
of the regimen including addition of saquinavir did not improve the response.
Successful salvage therapy in PI experienced patients may require intervention
when HIV RNA is low; waiting until viral load is high may prevent success even if
dual PI regimens with new nucleosides are used.
S12319 Lipid abnormalities associated with use of protease
inhibitors: Prevalence, clinical sequalae and treatment
Keith Henry. 640 Jackson St, Suite 123N, St Paul, MN, USA
Lipid abnormalities are increasingly linked to use of protease inhibitors (PI).
Objective: To assess the status of cholesterol (mg/dl) and triglyceride (mg/dl)
levels in patients receiving PI therapy, identify clinical sequalae, develop and implement a treatment strategy based on National Cholesterol Education Program
Guidelines (NCEP).
Methods: Chart audit of HIV+ patients on various antiretroviral regimens,
lipoprotein profile (LP) for persons with elevated lipids, identify clinical sequalae,
and implement NCEP treatment.
Results: The average cholesterol level in patients receiving no treatment (n =
17) was 161 mg/dl while in non-PI treated patients (n = 26) the average cholesterol
was 181 mg/dl. For 25 patients receiving double PI treatment (ritonavir/saquinavir)
the cholesterol increased from 162 to 239v mg/dl while for persons on a single PI
regimen (n = 31) the cholesterol increased from 179 to 211 mg/dl. Twenty-eight
persons (of 121 patients on a PI regimen = 23%) were identified to have abnormal
LP levels requiring intervention. Utilizing NCEP, 13 patients began a diet/exercise
regimen (mean cholesterol = 249 mg/dl; mean triglyceride = 319 mg/dl). Fifteen
patients were started on gemfibrozil at a dose of 600 mg po bid (mean cholesterol
= 357 mg/dl; mean triglyceride = 1879 mg/dl). After two months on gemfibrozil,
the mean cholesterol = 261 mg/dl and the mean triglyceride = 1244 mg/dl. Six
patients have not responded, three of whom have been started on atorvastatin.
Recent clinical events in our PI treated patients include four pancreatitis, three
new onset diabetes, one myocardial infarction and one new onset angina.
Conclusions: LP abnormalities have been observed in a significant portion of
persons receiving PI therapy. At this time, it is unclear whether current NCEP
based treatment will be effective in lowering LP levels. Further studies are needed
regarding the mechanisms involved in the LP dysfunction and the long-term clinical implications.
| 12320 Effectiveness of combination with protease inhibitors in
the treatment of HIV-infected children
Miguel Angel Clavo Bermudez1, Desamparados Perez-Tamarit2, M.C. Otero2,
R. Sirera3, J. Cordoba4, A. Gonzalez-Molina3, F. Asensi2. 1Av. Jouaquin Ugarte,
14N7 Valencia; 2lnfecciosos-Hopital Infantil La Fe, Valencia;
3lnmunologia-Centro Invest. Hospital La Fe Valencia; 4Biol. Molecular
Microbiologia Hop. La fe Valencia, Spain
Objective: To know the effectiveness of protease inhibitors (Indinavir and Ritonavir) in HIV-infected children who had not been previously treated with these
drugs.
Methods: 22 HIV-infected children (11 males and 11 females) between 1-15
years old were randomly administered Indinavir (350 mg/m2/8 h.) or Ritonavir
(350 mg/m2/12 h.) in combination with different nucleoside analoges reverse
transcriptase inhibitors of for at least 2 months. The viral load (Log1o copies/ml
RT PCR assay) and CD4+ lymphocyte (percentaje) were evaluated before and
6 to 8 weeks after beginning treatment. CD4 counts were assesed by two-color
flow cytometry.
Results: 22 (37.9%) of 58 controlled HIV-infected children belonging to Groups

A, B, or C of the CDC-94 classification were evaluated. The mean age was 7.4
~ 3.6 years (mean ~ sd). The mean duration of antiretroviral treatment prior
to the association of the protease inhibitor was 11.5 months (range between 1
and 46 months). A significant decrease in the viral load (4.7 ~ 0.8 Logio vs
3.8 ~ 1.1 Logo1 post-treatment, p < 0.01 Wilcoxon-test) was observed. In 6
cases (27.2%) the viral load remained at non-detectable levels and 5 (22.7%) an
increase in viremia was observed and was maintained even after 4 months. The

mean value (percentage) of CD4 lymphocytes increased 8 weeks after beginning
the combination treatment with Ritonavir or Indinavir in 19 children (86.3%) (15:
19.4% vs 19.1 ~ 8.4% post-treatment, p - 0.01 Wilcoxon-test).
Conclusions: Protease inhibitors associated with other antiretrovirals increased CD4 percentages, decreased the viral load and were well tolerated.
The influence that intercurrent infections, vaccinations (influenza), the probable
resistance of HIV to the treatment, together with its strict compliance, have on the
viral load will have to be evaluated in the 5 HIV-infected children with increases
in viremia.
112321 Phase 2 study of amprenavir, a novel protease inhibitor,
in combination with zidovudine/3TC
Richard Haubrich. USCD Treatment Center, 2760 Fifth Ave Suite 300, San
Diego CA, USA
Objective: To assess the safety, tolerance and antiviral activity of 141W94 (Amprenavir, USAN approved) in combination with zidovudine (ZDV)/3TC in patients
with HIV infection and to generate data to facilitate dosage selection in phase 3
studies.
Methods: Adults with a viral load >10,000 copies/ml, a CD4+ count of,150/mm3 and no previous 3TC or protease inhibitor treatment were randomised
to amprenavir 900 mg bid, 1050 mg bid, 1200 mg bid in combination with ZDV
300 mg bid/3TC 150 mg bid. All patients received treatment for a minimum of 48
weeks unless withdrawn.
Results: 48 male and 12 female patients (median age 35 years) were treated.
8% were CDC class C and 66% had not received antiretrovirals in the previous 6
months.
Preliminary results to 24 weeks for the Intent to Treat population are presented:

141W94 Dose Logo1 HIV RNA Copies/ml
(bid) Baseline A from Baseline
n Median n Median
900 mg 20 5.15 16 2.31
1050 mg 20 4.78 18 -1.95
1200 mg 20 4.88 11 2.35

CD4+ cells/mm3
Baseline A from Baseline
n Median n Median
18 382 14 135
20 312 18 99
20 405 11 117

Clinical adverse experiences occurring in >15% of patients were gastrointestinal, headache, malaise, fatigue, neuropathy and cutaneous reactions, were
generally mild to moderate in intensity and of a similar order as reported with
other protease inhibitors.
Conclusions: Amprenavir, at each of the doses tested, was generally well
tolerated and showed excellent antiviral activity in combination with ZDV/3TC.
S12322 Effect of highly active antiretroviral treatment (HAART)
on neutrophil and monocyte function
Claudio M. Mastroianni, F. Mengoni, M. Lichtner, C. D'Agostino, G. Forcina,
A. Corpolongo, V. Vullo. Dept Infect Trop Dis, La Sapienza University, Poclinico
Umberto 1, 00161 Rome, Italy
Objectives: To evaluate the effect of highly active antiretroviral treatment
(HAART) regimens (two nucleoside analogs plus ritonavir or indinavir) on the
polymorphonuclear leukocyte (PMN) and monocyte function in ten HIV-infected
patients with CD4+ T-cell counts 20-500/mmc.
Design: Prospective, longitudinal study.
Methods: Luminol-dependent chemiluminescence (LDCL) production of PMNs
and monocytes under stimulation with opsonized zymosan (ZYM) (1 mg/ml), phorbol myristate acetate (PMA) (4 mM), Candida albicans (CAND), and Mycobacterium avium-complex (MAC) (multiplicity of infection = 20:1) was measured at
baseline, 4 and 12 weeks. PMNs (2 x 105) and monocytes (1 x 106) were
incubated with the different stimuli at 37 C in presence of luminol (80 mM). LDCL
results were expressed as relative light units (RLU)/cells and were correlated with
CD4+ T-cell count and viral load (VL: plasmatic HIV-1 RNA, Amplicore Roche).
Results: Data obtained (mean values) are shown in the table:

Weeks VL log CD4+

0
4
12

3.70
ND
ND

213
278
305

PMNs Monocytes
PMA ZYM CAND MAC PMA ZYM CAND MAC
0.27 0.93 1.1 0.79 0.36 5.7 1.4 0.6
0.69 2.9 3.7 2.3 0.45 5.1 2.4 1.1
1.17 3.87 5.19 2.13 0.61 10.78 7.86 3.18

Not detectable
Conclusion: Short term administration of HAART significantly increased oxidative metabolism of PMNs and monocytes in response to microbial stimuli. The
improvement of the functional activity of two critical components of the innate immune system, such as neutrophils and macrophages, may contribute to reduced
susceptibility to opportunistic infections in HAART-treated patients.
Supported by ISS-AIDS grant - 1997.