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

56 Abstracts 12222-12226

12th World AIDS Conference

0.19). The correspondent figures were 82%, 64% and 95% in the drug naive population (p = 0.04), and 77%, 77% and 81% in the non-naive population (p = 0.90).
In the 64 drug naive patients the proportions with HIV-RNA < 20 copies/mi at 6
months were 32% in the indinavir group, 32% in the ritonavir group, and 70% in
the combination groups (p = 0.02). All regimens were in general safe, but more patients in the ritonavir group (37%) stopped treatment due to side effects compared
with either the indinavir group (8%) or the combination group (13%) (p < 0.01).
Conclusion; Our preliminary analyses indicate that treatment with saquinavir
400 mg b.i.d. and ritonavir 400 mg b.i.d. daily in combination with two nucleoside
analogues is safe, and may have superior short term antiviral efficacy compared
with indinavir or ritonavir in patients not previously treated with antiretroviral drugs.
Results from a scheduled analysis in May 1998 will be presented.
290*/ 122221 Study of protease inhibitor combination in Europe
(SPICE): Saquinavir soft gelatin capsule
(SQV-SGC) plus nelfinavir (NFV) in HIV-infected
individuals
Graeme Moyle. On behalf of the SPICE study team; The Kobler Clinic, Chelsea
& Westminster Hospital, 369 Fulham Rd, London SW10 9th, UK
Background: Co-administration of NFV with SQV-SGC has been shown to increase plasma saquinavir (SQV) levels by 5-fold enabling reduction in saquinavir
dose without loss of antiviral activity.
Objective: To compare the antiviral activity and safety of SQV-SGC + NFV
with or without 2 nucleoside reverse transcriptase inhibitors (nRTIs) to that of
SQV-SGC + 2 nRTIs or NFV + 2 nRTIs in HIV-infected patients.
Methods: 157 protease inhibitor-naive patients with HIV-RNA > 10,000
copies/mL and able to start at least one new nRTI were randomized to A)
SQV-SGC 1200 mg tid + 2nRTIs (n = 26), B) NFV 750 mg tid + 2nRTIs (n = 26),
C) SQV-SGC 800 mg tid + NFV 750 mg tid + 2 nRTIs (n = 51) or D) SQV-SGC
800 mg tid + NFV 750 mg tid (n = 54). Crossovers were allowed for intolerance or,
after 16 weeks, virologic non-response or relapse. All patients were considered
for protease genotypic sequencing at 16 or 24 weeks based on viral load.
Results: Patients had a mean baseline HIV-RNA of 4.8 loglo copies/mL and CD4
count of 301 cells/mm3. 54% were treatment-naive. Of the treatment-experienced
patients enrolled, 3 (25%), 2 (17%), and 6 (25%) in arms A, B & C, respectively,
started 2 new nRTIs. All patients have completed 32 weeks of study therapy. Preliminary data indicate that at week 32, the mean HIV-RNA reduction from baseline
(UltraSensitive) was 2.48, 2.23, 2.46, 2.39 loglo copies/mL for arms A-D, respectively. The proportion of patients with HIV-RNA < 400 copies/mL (Amplicor") was
70%, 55%, 83%, 69%, respectively, while the proportion below 50 copies/mL (UItraSensitive) was 55%, 50%, 70%, 39%, respectively. CD4 counts increased by
a mean of 92, 73, 134, 161 cells/mm3, respectively. Study therapy was generally
well tolerated. 38 patients were eligible to crossover to another arm; 32 for virologic
failure and 6 for toxicity. After 16-24 weeks' therapy, key resistance mutations were
detected in isolates from 10 patients (90 M: 6; 48V: 0; 30N: 4).
Conclusions: SQV-SGC and NFV + 2 nRTIs demonstrate potent viral load
suppression in a heterogeneous population of pre-treated and nalve patients.
48-week data will be presented.
12223 An open-label, randomized, comparative study of d4T +
3TC + IDV versus ZDV + 3TC + IDV in treatment naive
HIV-infected patients (START I)
Roy Gulick', K. Squires2, W. Powderly3, J. Santana,4, J. Esinhart5,
N. Schoellkopf5, M. Stevens6. 1Cornell University Medical College 119 West
24th Ground Floor NY NY 10011; 2University of Alabama Birmingham
Birmingham AL; 3 Washington University St Louis MO; 5PharmaResearch
Corporation Wilmington NC; 6Bristol-Myers Squibb Plainsboro NJ, USA, 4San
Juan AIDS Program San Juan, PR, Puerto Rico
Objectives: To evaluate the level of viral suppression in patients taking
d4T+3TC+IDV or ZDV+3TC+IDV using the Chiron bDNA assay (detection limit
(DL) < 500 copies/mL) and the National Genetics Institute (NGI) ultrasensitive
assay (DL < 50 copies/mL).
Design: This ongoing, open-label, randomized study evaluates the virologic
and immunologic effects of d4T+3TC+IDV as compared to the combination of
ZDV+3TC+IDV. Eligible patients are treatment naive with CD4 _ 200 cells/mL
and HIV RNA > 5,000 copies/mL (Chiron bDNA assay).
Methods: An interim analysis was performed 24 weeks after enrollment of half
of the total patients (100 of 200). Available samples taken at weeks 12 or 24 that
contained <500 copies/mL by the Chiron bDNA assay were further analyzed by
the NGI ultrasensitive assay (DL < 50 copies/mL).
Results: Preliminary results are presented in the table below.
Patients with virus below detection limits (bDNA < 500 copies/mL, NGI < 50 copies/mL) by
treatment arm and assay

S12224 Long-term comparison of BID and TID dosing Viracept
(nelfinavir) in combination with stavudine (d4T) and
lamivudine (3TC) in HIV patients
Annakatrin Petersen1, Margaret Johnson2. 1Agouron Pharmaceuticals, Inc.
10350 N. Torrey Pines Rd., La Jolla, CA 92037, USA; 2Royal Free Hospital,
London, England
Objective: To assess the safety, efficacy and pharmacokinetics of Viracept in a
BID dosing regimen as compared to the approved TID regimen.
Design: Phase III multicenter, randomized study: the original design is a fourgroup comparative trial of four nelfinavir dosing regimens, 750, 1000, and 1250
mg BID (Blinded) vs. 750 mg TID, all in combination with standard doses of d4T
and 3TC, for a total duration of up to 96 weeks. A total of 289 patients have been
enrolled. Recently the protocol has been amended to compare only 1250 mg BID
vs 750 mg TID in a total of 360 patients is still accruing.
Methods: Adult patients with confirmed HIV infection who are 3TC naive and
have less than 6-months of prior nucleoside antiretroviral therapy are included.
Mean baseline viral load is 5.3 log copies/ml and mean baseline CD4+cell count
is 388 cells/mm3 Pharmacokinetics were done after 4 and 8 weeks of treatment.
Results: Favorable drug exposure levels were achieved at both the 1250 mg
BID and the 750 mg TID doses. A total of 278 patients are included in the 'Time-toEvent' analysis applied to determine the durability of the treatment response in
terms of detectable (< 400 copies/ml) plasma HIV-RNA levels. Approximately
80% of all patients in both dosing regimens responded. This initial response
was maintained in 93% at 32 weeks. No serious drug-related adverse events
occurred. Moderate or severe diarrhea was reported in 12% and 13% of patients
treated with BID and TID respectively, but only one patient was discontinued for
this reason. Complete viral load data and CD4+ cell counts from baseline to week
48 will be available for the majority of the patients.
Conclusions: At 32 weeks, the BID regimen appears to be as effective and
safe as the TID regimen.
S12225 An open-label, randomized, comparative study of d4T +
ddl + IDV versus ZDV + 3TC + IDV in treatment naive
HIV-infected patients (START II)
Joseph Eron', D. Peterson2, R. Murphy3, J. Pottage4, J. Mauney5,
N. Schoellkoph5, M. Stevens6. 1547 Burnett-Womack, University of NC, Chapel
Hill, NC; 2UT Southwestern Medical Center, Dallas, TX; 3Northwesten
University, Chicago, IL; 4Chicago Center for Clinical Research, Chicago, IL;
5Pharma Research Corporation, Morrisville, NC; 6Bristol-Myers Squibb,
Plainsboro, NJ, USA
Objectives: To evaluate the level of viral suppression in patients taking d4T +
ddl + IDV or ZDV + 3TC + IDV using the Chiron bDNA assay (detection limit (DL)
<500 copies/mL) and the National Genetics Institute (NGI) ultrasensitive assay
(DL < 50 copies/mL).
Design: This ongoing, open-label, randomized study evaluates the virologic
and immunologic effects of d4T + ddl + IDV as compared to the combination of
ZDV + 3TC + IDV. Eligible patients are treatment naive with CD4 > 200 cells/mL
and HIV RNA > 10,000 copies/mL (Chiron bDNA).
Methods: An interim analysis was performed 24 weeks after enrollment of half
of the total patients (100 of 200). Available samples taken at weeks 12 and 24
that contained <500 copies/mL by the Chiron bDNA assay were further analyzed
by the NGI ultrasensitive assay (DL < 50 copies/mL).
Results: Preliminary results are presented in the table below.
Patients with <500 copies/mL (bDNA) and those with <50 copies/mL (NGI) plasma HIV RNA
by treatment arm and assay
d4T + ddl + IZD ZDV + 3TC + IDV
N bDNA NGI N bDNA NGI
Week 12 45 33(73%) 16(36%) 38 30(79%) 15(39%)
Week 24 34 23 (68%) 12 (35%) 30 23 (77%) 15 (50%)
N is the numbers of patients tested using both assays
Conclusion: This preliminary data suggest that a combination of 2 RTIs and a
PI might not fully suppress viral replication in a large proportion of patients in this
study. The long term clinical implications of this lack of full suppression requires
additional study.
S12226 Stavudine (d4T), didanosine (ddl), and nelfinavir
combination therapy in pretreated HIV-patients: Antiviral
effect and safety in an ongoing study
Ulrich Hengge, N.H. Brockmeyer, V. Exner, A. Beckman, M. Goos. Dept. of
Dermatology STD-Unit, Univ. of Essen, Essen, Germany
Objectives: A total of 53 subjects experienced to various RT- and protease
inhibitors who were treatment-naive to d4T, ddl and nefinavir were enrolled to
receive d4T 40 mg BID + ddl 200 mg OD as liquid formulation + nelfinavir 750

mg TID in an open-label fashion.
Results (see table): At week 24, HIV RNA levels below 500 copies/ml were
reached in 10/33 (30%) subjects.
Increases in HIV-1 RNA load were detected in non-compliant subjects (viral
resistence tests ongoing). Adverse events were: 3 cases of pancreatitis (1 death)
and 3 cases of lipase elevation, probably related to ddl; 2 cases with hypertriglyceridemia (>1700 mg/dl) and hypercholesterinemia (>400 mg/dl), which have not

d4T+3TC+IDV
N bDNA NGI

ZDV+3TC+IDV
N bDNA NGI

Week 12 42 32 (76%) 14(33%) 41 33 (80%) 22(54%)
Week 24 39 34 (87%) 19 (49%) 40 32 (80%) 24 (60%)

N is the number of patients tested using both assays.
Conclusion: This preliminary data suggest that a combination of 2 RTIs and a
PI suppress viral RNA to <50 copies/mL in about 50% of the patients. The long
term clinical implication of this viral suppression requires additional study.