Abstracts Vol. 1 [International Conference on AIDS (11th: 1996: Vancouver, Canada)]

Track B: Clinical Science

Mo.B. 1329 - Mo.B. 1333

patients, is defined by creatinine clearance, was studied Lamivudine was well tolerated in all
patients. Dialysis patients were studied between visits (inter dialysis) and on dialysis (intradialysis).
Pharmacokinetic results showed a linear
relationship between degree of renal
im p a irm e n t a n d la m iv u d in e c le a ra n c e. e, e,. s u. m,,,,
As renal function decreases, there is a "
concomitant decrease in lamivudine
total and renal clearance (CI/F and Cir)
reflected by an increase of 270% and
500% in AUC in patients with moderate /
and severe impairment respectively and I
an increase in elimination half life. Cmax. *
was increased by I120-140% in patients -,s,,
with renal impairment over healthy controls.This data support that obtained in,...N.n......*n,
a previous study in HIV infected renallyimpaired patients.
By virtue of its low molecular weight and relative lack of protein binding, lamivudine was
extracted by about 50% intra -dialysis (Dialysis clearance= O105mL/min).This was similar
the extraction ratio for urea, used as an interna standard of dialyser efficiency.
Intermittent 4h haemodialysis increased mean Cl/F from 64 to 88mL/min. However, in
half (n 3) of the patients undergoing haemodialysis, Cl/F was similar when administered
inter or intradialysis. As renal function declines there is an increase in the amount of the
trans-sulphoxide metabolite.This is of no concern as it possesses no toxicity and is pharmacologically inactive.
In conclusion, dose reduction in patients with impaired renal function is required to attain
siresilar serum concentrations/exposure to non-impaired subjects and intermittent
haemodialysis does not warrant a further change in dose from that defined by creatinine
clearance.
Geofifrey J Yuen, Dept of Clinical Pharmacokinetics, Glaxo Wellcome, Five Moore Drive, PO Box
13398, Research Triangle Park, NC 27709, USA.Telephone: [phone] fax:[phone]

Outcomes (n): NAOC (81)
Present at PHI: RH 95% C
Fncephalitis 18.3 (3.5 -97 I
Sup.clavadeno. 4.8 (I.4 16.8)
lepress on 3,8 (1.3-!i.0)
Oral canddiasis 3.4 (.8 63)
Lethargy 1.7 (I.0 2.8)

AIDS 0632
Prese at P-I: RH2 95% CI
Sup.dava deno. 3.2 (I. 9.7)
Phary s t, l
or Soi e throat 2.8 l. /

Death (54)
Present at PHI: RH3 9 CI
Oesophagitis 2 87.
Supclavadeno 85 ().6 278)
Pha yngitisur
SWre thr it s.6 I, 6 7)
W eight io"s 12.1 (1.)-6.3 )

RH adjusted for:I centre, PHI treatments (AZT and/or symptomatic treatment), age, sex
and year of infection; 2 same as 1+ AZT before AIDS and primary PCP prophylaxis; 3
same as I + AZT any time, primary and secondary PCP prophylaxis.
Conclusions: Supraclavicular adenopathies, buccal and/or oesophageal symptoms are associated with NAOC, AIDS and death. Neurological symptoms are only related to first NAOC.
These observations may be linked to vanous pathogenetic mechanisms of HIV during PHI,
including the early neurologic Tropism of HIV
Philippe Vanhems, MD, 3840 St -Urbain St., Hotel Dieu de Montreal, Pav. Cooper;
Montreal, Quebec, H2W I T8 Canada Tel: [phone] Fax: [phone]
Email:[email protected] ca
Mo.B.1331
TRIPLE DRUG COMBINATION IN PRIMARY HIV-I INFECTION
Lafeuillade Alain*, Pellegrino P., Poggi C., Coses O.*, Profizi N.*,Tamalet C.**. Geri
HospitalToulon, **Timone Hospital, Marseille, France
Objective: to describe the evolution of HIV I viremia, clinical signs and CD4+ T cells co
in patients presenting primary HIV-I infection (PHI) treated with a triple-drug conbination.
Methods: 6 HIV-I infected patients have been recently diagnosed with PHI (3 females, 2
males). A combination of oral Zidovudine (ZDV, 200 mg tid) + didanosine (ddl, 200 mg
bid) and Lamivudine (3 TC, 150 mg bid) was started 10 days after the first symptoms of
PHI in 3 cases, 15 days in I case and 30 days in the 2 others. HIV-I RNA was quantified in
plasma regularly after therapy was introduced, and when possible on prior stored samples
before diagnosis was established, with a PCR kit (Amplicor Moniton Roche Diagnostic
Systems, France).

Mo.B. 1329 Results: a dramatic decrease of HIV I RNA titres was observed with therapy in one ca
PHARMACOKINETICS OF CASTANOSPERMINE IN ASYMPTOMATIC HIV-POSITIVE HIV I RNA levels dropped below the cutoff after 14 days. In the 5 others the first phas
PATIENTS TREATED WITH MDL 28,574A DURING PHASE I TRIALS decline exhibited a mean half-life of 2.3 ~ 1.3 days.Then a more progressive decline wa
Stoltz, Maxine L.*, McPherson, M.*, Frampton, M.*, Sidarous, E.*, Jacobs, M., Roth, H.t. observed in one case until day 150 when titres dropped below the cutoff, a plateau aro
*Hoechst Marion Roussel, Kansas City, MO, USA; tSaint Francis Memorial Hospital, San 2000 copies/ml was maintained in one case with 100 days of follow-up.This patient dev
Francisco, CA, USA; tParexel, Berlin, Germany oped a rapid CD4+ T cells depletion at that time (290 x 106/I) and admitted to take dc
Objective: MDL 28,574A, a castanospermine (CAST) derivative, is in development to pre- rarely Follow-up is limited in the 3 last cases more recently diagnosed.
vent progression of ARC and AIDS in HIV patients.The drug inhibits a-glucosidase I which Conclusion: A triple drug combination of ZDV + ddl + 3 TC can reduce HIV I viremia
alters glycoprotein processing, reducing infectivity and syncytial formation. Plasma pharmaco- during PHI in most cases.This effect could be able to modify the subsequent natural his
kinetics of CAST, the primary circulating species following treatment with MDL 28,574A, in of the disease. Follow-up of this series will be presented.
asymptomatic HIV+ patients, are presented. Docteur Alain LAFEUILLADE, Unite d'Infectiologie, H6pital Chalucet, F-83000 TOULON
Methods: Sinfle oral solution doses (i O-160 mg) and multiple doses given QDxl4 days (10-450 France.Tel: [phone]; Fax: [phone]
mg), were administered to groups of 3-6 patients. Plasma for CAST analysis was collected for 72 h
after treatment. trough concentrations were measured during multiple dosing. CAST was quantified Mo.B. I 332
using an FPI C/MS method; the quantitation limit was 5 ng/mL. MA TRIPLE NUCLEOSIDE ANALOGUE COMBINATION IN FOUR PATIENTS WITH
Results: After single doses of MDL 28,574A, CAST was rapidly detected in plasma with A TRIMARY HIV-PLE NUCLEOSIDE ANALOGUEWARDS COMPLEBINATION IN FOUR PATIENTS WITHN
peak concentrations occurring at 12 h. Over the 16 fold single dose range, proportionate SaimotAG-, Simon F*, Landman R, Girard PM**, Fauveau V**, Mariot P**, Leibowitch
increases in Cmax and AUC[infinity] were observed. At the higher single dose levels (80 J* Mathez D***. *Hptal Bichat-Claude Bernard;'*H6pital Rothschild, Pris; H6p
and I 60 mag), the terminal t was 18 h. Plasma pharmacokinetics of CAST after multiple
doses of MDL 28,574A showed that increases in Cmin,ss, Cmax,ss, and AUC,ss values were Raymond Poincar, Paris, France
generally proportional to dose as shown below. Also, steady state apparent oral clearance Objectives: By introducing a convergent combination ofThymidine, Cytidine, Adenosine
and t values were constant across the 45-fold dose range, analogues altogether within 6 weeks in patients wth primary retrovira infection, to obt
k i rxaciitVi it) u fi

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112

Mean CASIt Steady State Pharmacokinetic Parameters
Parameter 10 mg 20 mg 40 mg 80 mg
Cimn,ss (/mL) 8 II 23 29
Cmax,ss (ng/mL) 266 520 1075 1720
AU(,ss (n~g h!mL) 1004 1749 3612 6532
tsi 2 (h) I 27 30 16

s Following O
160 mg
70
3731
13304
i21

al Doses of MDL 28,_
240 mg 360 mg
I110 179
5757 7305
21538 321l4

74A
450 mog
191
10544
39805
14

such a bloc Kae o H I_ v activity in vivo as to stop treatment ater I Z mont s ori ts nitiation.
Patients and methods:Three men, I woman (aged 35-38) received zidovudine (AZT) (250
nmg tid), didanosine (ddl) (200 mg bid), and lanmivudine (3TC) (1 50 mg bid) during the
course of a clinically overt primary HIV I infection documented by both sequential Western
Blots and plasma viremias. Log HIV infectious blood cells/I 07 PBMCs [lower limit of detection 0.7(a)], and Log HIV RNA copies/ml plasma (Amplicor Monitor Roche~, 36 cycles,
limit of detectionl(b) were sequentially determined in real time.
Results:

Conclusions: Single dose and steady-state pharmacokinetics of CAST are linear and
steady state pharmacokinetic parameters are readily predictable from the single dose
kinetics of CAST
Maxine L. Stoltz, PhD: Hoechst Marion Roussel; PO Box 9627-8045; Kansas City, MO 64 I 37
Tel: [phone]; Fax: [phone]; Email: [email protected]
Mo.B. 1330
OCCURRENCE OF NON-AIDS OPPORTUNISTIC COMPLICATIONS,AIDS AND
DEATH BY CLINICAL PRESENTATION OF PRIMARY HIV INFECTION.
Vanhems Philippe-, Allard R1, LambertJ, Cooper DA2, Hirschel B3, Carr A2, Perrin L3,
Vizzard J 2, Kinloch-de Lobs S3, Hoen B. 1 U. of Montreal, Montreal, Canada2 St Vincent's
Hospital, Sydney Australia, 3lnfect. diseases, U. of Geneva,Geneva, Switzerland, 4Infect. dis
eases, U. of Nancy Nancy France.
Objective: to assess the HIV disease progression and survival by clinical presentation of primary HIV infection (PHI).
Methods: 2 18 patients with a documented symptomatic PHI were compared to 42 asymptomatic seroconverters (dates known within I year). 242 patients were male and 204
homosexual. Cox's m odel was used to estimate the relative hazard (RH) of occurrence of
non AIDS opportunistic complications (NAOC), of AIDS (1987 CDC definition) and of
death, by sign/symptom during PHI.
Results: The ien duration of PHI was 25. I days with no difference by sex or by risk factorThe adjreusted RH (95% Cl) of PHI signs/symptoms significantly associated with the outcomes are reported below:

Patients Weeks 0
C 3.54 2.E
F 209 0.
K 3.19
G RNA(b) 6.90 3.
C 4.74 2
F 4./8 3.
K 4.4

4 8
095 0.78

24 7 2
0.70 0.70 0.70

i0

242
3.42
2.41

1./2 100

Conclusion: In all 4 patients, virus became undetectable in either cells or plasma or both by
weeks 12-16 of treatment. Patient G has been off antivirals for 3 months since week 52
without recurrence of retroviral activity in blood cells or plasma.
A.G. Saimot, H6pital Bichat-Claude Bernard, 46, rue Henri Huchard, 75018 Paris, France
Tel: (33-1I) 40.25.78.07, Fax (33 I) 42.29.53.00
Mo.B. 1333
CRYPTOSPORIDOSIS COMPLICATING A PRIMARY INFECTION: FIRST CASE
Jobard JM., dMedecine B, Briancon, France
HIV primary infection which usually escapes notice, is discovered in 70 % of cases through a
classic influenzal syndrome.The symptoms are very rarely ostentatious and a mononucleosic syndrome is associated with an important transitory depletion of CD4s. In this report
the first case of cryptosporidosis is studied during an ostentatious and serologically evolutive primary infection.The patient aged 42 was admitted to hospital in August 1994 after 10
days of profuse diarrhea accompanied by a high temperature and suffering from dehydra