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

12th World AIDS Conference

Abstracts 22403-22407 345

22403: Table

AZT + 3TC + IND

D4T + 3TC + IND

CD4 mean
Log RNA mean
RNA - 500 (- 20 c/ml)

Baseline
43 (1-124)
4.95 (3.4-5.9)
0/27

Month 1
106 (9-206)
2.96 (2.7-5.3)
20/24

Month 4
157 (20-438)
3.03 (2.7-5.5)
19/24

Month 8
184 (24-506)
3.02 (2.7-4.7)
13/21 (11/21 )

Baseline
62 (3-170)
5.01 (3.6-5.9)
0/20

Month 1
159 (7-360)
3.06 (2.70-4.36)
11/19

Month 4
184 (32-421)
2.79 (2.70-3.95)
12/14 (9/14 )

Month 8
214 (36-567)
3.11 (2.7-5.1)
4/6

p - 0.05. p ~ 0.01 respect the baseline. No significant difference was found between the two groups; Three patients in each group were withdrawed of the study by adverse events.

[22403 AZT + 3TC + indinavir vs D4T + 3TC + indinavir for HIV
infection in pretreated patients with less than 200
CD4/mm3
Rafael Rubio', J. Martin, F. Pulido, A. Barrios, J. Alcami, J.R. Costa. 1Unidad de
Infeccion VIH 12 de Octubre Crra. de Andalucia Km. 5,400 28 041 Madrid, Spain
Objective: To assess the efficacy and tolerance, in pretreated patients witt less
than 200 CD4/mm3 of combination therapy with AZT + 3TC + IND vs D4T + 3TC
+ IND.
Methods: Comparative, non randomized study. All patients (n = 47) had previous antiretroviral therapy with AZT and/or DDI and/or DDC (median 27 months)
and were treatment-naive to D4T, 3TC and protease inhibitors. Plasma viral load
was assessed by the bDNA technique (Quantiplex HIV RNA, Chiron). In those
patients with viral load below 500 copies/ml an ultrasensitive assay (detection
level 20 RNA copies/ml) was performed (Ultrasens, ROCHE)
Results (see table above): The baseline characteristics were similar in both
groups.
Conclusion: Both regimens have a similar efficacy and tolerance in pretreated
patients.
22404 Pharmacokinetic interaction between nevirapine and
indinavir and correlation with antiviral activity
Robert Murphy1, J.P. Sommadossi2, M. Lamson3, P. Gagnier3, D. Hall3,
M. Myers3, A. Dusek3. 1North Western University, 303 East Superior ST# 828,
Chicago, IL; 2University of Alabama, Birmingham, AL; 3Boehringer-lngelheim
Pharmaceuticals, Ridgefield, CT USA
Introduction: Nevirapine (NVP) and indinavir (IDV) share the same metabolic
route through the P450 CYP 3A isoenzyme and thus have the potential of affecting the pharmacokinetics (PK) of each other. The clinical relevance of these drug
interactions is unknown.
Design: Prospective, open-label with formal pharmacokinetic phase.
Methods: 24 HIV-infected subjects on stable nucleoside or no therapy were
treated with IDV 800 mg q 8 hrs; after 7 days, NVP 200 mg qd was added for 14
days after which the dose was 200 mg bid. Therapy with both agents continued
for 58 wks. Intensive PK analy-ses were performed at days 7 and 36. HIV plasma
RNA, lower limit to 20 copies/mL, was measured at regular intervals.
Results: Median CD4 was 434/mm3, plasma HIV RNA was 3.51 log10
copies/mL. 19 subjects completed the 36 day PK study, 17 entered an extension
phase. At day 7, there was an 8-fold difference in IDV AUC and a significant
correlation observed between pre-NVP IDV AUC (r2 = 0.338, p = 0.023), IDV Cmin
(r2 = 0.312, p = 0.031) and plasma HIV RNA decline. At day 36, the differences
narrowed significantly. NVP caused a reduction in IDV Cmax (11%), Cmin (38%),
and AUC (28%), but IDV AUC was above the threshold (10 /1M hr) required for at
least a 1.0 log1o plasma HIV RNA reduction in all analyzed patients. Undetectable
plasma HIV RNA (. 20 copies/mL) were noted in 12/17 (70.5%) at 22 wks, and
11/17 (64.7%) at 58 wks or last visit.
Conclusions: IDV concentration decreases associated with NVP are most
prominent in subjects with high IDV concentrations at baseline. The addition of
NVP results in a viral load decline in all patients with IDV plasma levels still above
an effective antiviral theshold. These data suggest that indinavir dosing should
be dependent on drug exposure and not co-therapy with a CYP 3A inducer such
as NVP.
22405 Increase in the expenditure for antiretroviral drugs: Are
there any advantages?
Matteo Bassetti, A. Di Biagio, B. Rebesco, M.E. Amalfitano, G. Gatti, F. Fusco,
D. Bassetti. First Department of Infectious Disease, University of Genoa,
Ospendale San Martino, Largo R. Benzi 10, 16132, Genova, Italy
Background: In Italy protease inhibitors (IP) have been introduced in routine
clinical practice since the beginning of 1997. The inclusion of such drugs in the
list of available therapeutic agents has convulsed the hospital budgets. On the
other hand, the clinical, immunological and virological efficacy of these drugs is
well known.
Objective: To analyze the consumption and the cost of antiretroviral drugs,
ganciclovir and foscarnet in the years 1996 and 1997 in the largest Italian hospital
(2516 beds), Azienda Ospedaliera San Martino.
Design: We analyzed the consumption in drug units and the cost in USD of the
NRTI (AZT, DDC, DDI, 3TC, D4T), IP (saquinavir, ritonavir, indinavir), ganciclovir
and foscarnet in 1997 and we compared them with the consumption and cost
in 1996. It has to be pointed out that AZT, DDI and DDC can be purchased out
of the hospital. The number of HIV infected patients followed in our hospital is
approximately of 1000.

Results:
Year
Units of antiretroviral drugs
Cost of antiretroviral drugs in US$
Units of anti-CMV drugs
Cost of anti-CMV drugs in US$

1996 1997

94,975
135,147
2,337
56,124

860,688
1,550,911
348
8,878

The most prescribed antiretroviral drug has been indinavir (214,380 units)
while 3TC was associated with the highest expenditure (459,164 USD). The consumption of ganciclovir and foscarnet has considerably decreased in the second
semester of 1997 from 186 to 60 units for ganciclovir and from 102 to 0 for
foscarnet. The consumption of ganciclovir and foscarnet in 1997 has been of 246
and 102 vs. 1732 and 601 units in 1996, respectively.
Conclusions: Our analysis indicates that the year 1997 has been characterized
by an impressive increase of both the prescription and the cost of antiretroviral
drugs (NRTI and IP). On the other hand, the consumption and cost of drugs
utilized in the therapy of opportunistic infections, such as CMV, are appreciably
decreased. Whether the benefits, in terms of quality of life and prolongation of
survival, justify the increase of public expenditure should be the object of further
verification.
22406 Scenario of anti retroviral therapy (ART) in 25,000
HIV/AIDS individuals in Mumbai, India
Dattaray Saple, J.K. Maniar. Hon. Prof G. T Hospital, G.M. College, 11-c Oliver
Mansion, Mogul Lane Mahim, Mumbai, India
Aim: To study benefits of Triple Drug ART in HIV/AIDS population in India.
Method: During 1987-97, 25,000 HIV/AIDS patients attended our referal centre. 700 patients were started on ART, either single (AZT); or Two Drugs (AZT +
ddl/ddC/3TC) or Triple (AZT + 3TC + saquinavir/indinavir/retinovir) drug therapy,
after counselling for ART, CDC recommendation, CD4 count and virus load. 380
were on single, 220 on Two & 100 on Triple Drug Therapy. Analysis of 100
patients on Triple Drug Therapy - 60% stopped within a few months because of
high cost and preferred advertised cure by Alternative medicine (Initially patients
were enthusiastic because of Media); 20% did not show any clinical improvement
and/or in CD4 or Vital load; 18% showed improvement (Duration of ART from
6-16 months); 2% expired within 12 months, who had improved for first 9 months
and deteriorated thereafter and 2% showed severe side effects like bone-marrow
suppression and pancreatitis.
Results: (1) 2.8% could afford the various combination therapies. (2) 0.4%
could afford Triple Combination for 3-4 months while 0.08% for 6-16 months. (3)
20% on ART did not improve at all. (4) 0.01% were benefited by Triple Therapy
(6-16 months). (5) Media plays a major role. (6) Attraction of cure by quacks.
Conclusion: (1) 97.2% could not afford ART hence country like India should
start indigineous production of ART so as to make it affordable to a large section.
(2) Media should be realistic. (3) Prompt action is needed against the quacks.
22407] Cell fusion infectivity assay in patients receiving
retroviral therapy
Maria Angelica Watanabel12, J.C. Voltarelli3, P.V.B. Palma2, M.D. Orellana2,
V.B. Valente2, S. Kashima2, D.T. Covas2. ' Rua Tenente Catao Roxo 2501, Ribe
Irao Preto-Sao Paulo; 2FundaCao Hemo Centro Ribeirao Preto, Ribeirao Preto,
S.P; 3Fundagao Ribeirao Preto, Ribeira Preto, S.P, Brazil
Objectives: To study the capability of HIV-1 isolate from patients treated and non
treated with anti-retroviral therapy to form syncytia.
Design: Prospective study
Methods: Syncytia formation. Coculture of PBMC from HIV infected patient
and MT-2 cells. P24 detection was performed by MicroElisa system (Vironostika -
Organon Teknika) in the patient plasma and culture supernatant. The integrity of
chemokine receptor (CCRS) was evaluated by polimerase chain reaction (PCR).
CD4+ cells was quantified by flow citometry (Becton Dicknson).
Results: We studied 34 patients treated with three anti-retroviral drugs and 6
patients not treated. Thirty patients of treated group did not presented p24 antigen
in the plasma but this antigen was present in the supernatant of co-culture from
all patients that developed syncytia. Twenty three percent of patients treated did
not develop syncytia formation and 54% showed increment of CD4+ cells. All
the patients not treated presented p24 antigen in plasm and culture supernatant
and developed syncytia before 2 weeks of culture. Seven percent of all patients
presented deletion on CCR5 from peripheral blood mononuclear cell..
Conclusion: In spite of absence of p24 antigen in the plasma of patients submitted to antiviral polychemmotherapy, the present study showed development
of syncytia in three quarters of the patients. This finding indicates a dissociation
between viremia and intracellular infection in treated HIV-infected patients.