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

12th World AIDS Conference

Abstracts 12227-12231 57

Data (median, range) after 6 months of therapy Conclusions: In this highly antiretroviral experienced population subjects that
Pretreatment Week 12 Week 24 Change were switched from regimens containing ZDV to those containing D4T achieved
n = 53 n = 51 n = 33 clinically significant improvements in HIV RNA copies and CD4 counts.

Median CD4 (cells/mm3)
Median CD4 (%)
Median HIV RNA
(log io)
CD4/CD8 ratio

162 259
(0-933) (6-1667)
12.2 15.2
(0.2-49.6) (0.6-48.5)
4.9 2.7
(2.7-5.9) (2.7-5.6)
0.2 0.3

392
(11-2233)
20.0
(2.8-53.6)
2.7
(2.7-5.3)
0.4

+230
+7.8#
-2.2.

p - 0.0005; #p - 0.001
yet been reported, 14 episodes of loose stools, one case of grade 3 depression,
and one case of grade 3 allergic reaction to nelfinavir.
Conclusion: In conclusion, these preliminary findings suggest that d4T+ddl+
nelfinavir combination therapy in pretreated patients have potent antiviral effects,
but subjects need to be followed closely for the occurrence of adverse events.
S12227 ALBI (ANRS 070): A randomized controlled trial to
evaluate the efficacy and safety of AZT/3TC vs alternating
d4T/ddl and AZT/3TC vs d4T/ddl
Jean-Michel Molina, V. Journot2, F. Ferchal1, I. Pellegrin3, C. Rancinan2,
M.N. Sombardier1, J.M. Decazes'. Department of Infectious Diseases, 'Saint
Louis Hospital, Paris; 21NSERM U330, Bordeaux; 3Laboratoire de Virologie,
Bordeaux, France
Objectives: To determine whether alternating combinations of nucleoside analogues increase the antiretroviral effect associated with each combination alone.
Design: An unblinded, randomized controlled trial in which 3 treatment regimens were compared.
Methods: 151 antiretroviral naive patients with >200 CD4 cells/mm3 and a
plasma viral load between 4 and 5 loglo copies/ml were randomized to receive
either AZT/3TC for 24 weeks (group 1), d4T/ddl for 12 weeks then AZT/3TC for
12 weeks (group 2), or d4T/ddl for 24 weeks (group 3). Patients were assessed
monthly for viral load, CD4 counts and safety.
Results: The mean baseline viral load (logio copies/ml, Chiron Quantiplex RNA
HIV-1, 2.0) was 4.31 for group 1, 4.24 for group 2, and 4.13 for group 3, while
the median baseline CD4 count (cells/mm3) was 388, 383 and 382 respectively.
Results at 24 weeks are shown below.
Viral load (loglo copies/ml)

Mean decrease
Patients - 500 copies (%)
Mean CD4 increase (cells/mm3)

Group 1 (n = 51) Group 2 (n
1.28 -1.31
43 59
+62 +115

49) Group 3 (n = 51) p
-1.37 0.65
90 0.001
+125 +0.02

S12229 ADAM study. Induction-maintenance therapy in HIV-1
infection: Early results
Monique M.E. Reijers', G.J. Weverling', R.W. Ten Kate2, P.M.J. Frissen3, F. De
Wolf1, M. Scmuitemaker4, J.M.A. Lange'. Natec, AMC, MEI BE RGDREEF 9
1105 A2, Academic Medical center-Natec, Amsterdam, 2Kennemer Gasthuis,
Maarlem; 30NZE Lieve Vrouwe Gasthuis, Amsterdam; 4CLB -Clinical
Viro-lmmunology, Netherlands
Background: Regimens containing at least 3 antiretroviral agents have been
shown to produce dramatic reductions in HIV-1 RNA levels. However, the long
term effectiveness of such regimens can potentially be compromised by drug
toxicity and poor adherence. The purpose of this study is to explore the feasibility
of induction-maintenance therapy in long-term suppression of viral replication.
Methods: ADAM is a multicenter, randomised, open-label study, investigating
26 weeks induction therapy (d4T (40 mg bid) + 3TC (150 mg bid) + SQV (600
mg tid) + NFV (750 mg tid)) followed by maintenance therapy (either d4T + NFV
or SQV + NFV) or prolonged induction therapy in HIV-1 infected subjects with
>200 CD4~ cells/mm3, >1000 HIV-1 RNA copies/mL and no previous exposure
to anti-retrovirals. Subjects are randomised to the 2-drug arms or the prolonged
induction arm after 26 weeks only if viral load is <50 copies/mL at both weeks
24 and 25. The primary end point is reduction of plasma HIV-1 RNA (<400
copies/mL).
Results: 56 subjects have been enrolled since March 1997. At baseline the
median CD4+ cell count was 420 cells/mm3 (IQR 320-510), median CD81 cell
count was 1100 cells/mm3 (IQR 850-1510), and median HIV-1 RNA was 4.6
logo1 copies/mL (IQR 4.2-5.1). Except for 2 cases of elevated liver enzymes,
no adverse events led to study discontinuation. At week 8 the median CD4+ cell
count was 570 cells/mm3 (IQR 460-660), no change was observed with respect
to the CD8+ cell count, median HIV-1 RNA decreased to <50 copies/mL (IQR <
50-375). 26 of 27 subjects (96%, 95% C.I. 81-100%) could be randomised since
HIV-1 RNA concentration in the plasma was <50 copies/mL at weeks 24 and 25.
At a follow-up of 10 weeks after randomisation (n = 10), no virologic failure was
observed in either arm.
Conclusions: The quadruple induction regimen was well tolerated and led to
rapid suppression of viral replication to below 50 copies/mL. The absence of
immediate viral breakthrough is encouraging for the feasibility of induction-maintenance therapy. Data with extended follow-up will be available at the time of
conference.
127* / 12230 Safety and activity of abacavir (1592, ABC) with
3TC/ZDV in antiretroviral naive subjects
Margaret Fischl', S. Greenberg2, N. Clumeck3, B. Peters4, R. Rubio5,
B. Pobiner6, L. Verity7. 'Department of Medicine, Miami, Florida; 2Baylor
College of Medicine, Houston, TX; 6Glaxo Wellcome Inc., Research Triangle
Park, NC, USA; 3CHU, Saint-Pierre, Brussels, Belgium; 4Un. Med. & Dent.
Schls. of Guy's & St. Thom. Hospital, London; 7Glaxo Wellcome Plc., London,
UK; 5Hospital Doce de Octubre, Madrid, Spain
Objectives: Assess safety and activity of ABC/3TC/ZDV vs. 3TC/ZDV at 16 and
48 weeks (wks) of therapy.
Design: Randomized, double-blind phase III clinical trial.
Methods: 173 HIV-infected, antiretroviral treatment naive subjects who had
>100 CD4+ cells/mm3 were randomized to receive ABC 300 mg bid or placebo
and 3TC 150 mg bid + ZDV 300 mg bid. Subjects were stratified by screening
plasma HIV-1 RNA level (vRNA) and evaluated at wks 2, 4, and then every 4 wks.
At wk 16 and then every 8 wks vRNA (Roche Amplicor) was provided in real-time.
Subjects with vRNA >400 copies/ml (level of assay detection) at or after wk 16
were eligible to continue blinded therapy, receive open-label ABC with approved
antiretroviral drugs or discontinue study drugs. The study was powered to detect
a difference in proportion of subjects with vRNA <400 copies/ml of 0.25 and 0.50
in the 3TC/ZDV and ABC/3TC/ZDV arms, respectively.
Results: Study drugs were well tolerated. Four subjects discontinued therapy
for adverse events (two for a syndrome characteristic of ABC hypersensitivity).
Pretreatment median vRNA was 32,257 copies/mi (3% were <400 copies/ml)
and CD4+ count was 438 cells/mm3. Preliminary, blinded data at wk 16 were
available for 144 subjects; median vRNA was <400 copies/mi and 67% had <400
copies/ml. Unblinded 16 wk safety and activity data will be provided.
Conclusions: Abacavir was well tolerated and the majority of antiretroviral
treatment naive subjects receiving combination nucleoside therapy at wk 16 had
vRNA below the detection limit of the assay.
S12231 Retained effectiveness of protease inhibitor (PI) therapy
(Rx) following "protease sparing" nevirapine/nucleoside
(NVP/nuc) combination therapy
Robert Curry, Patrick Robinson, S.A. Hussain, M.W. Myers, P.A. Robingson.
Boehringer Ingelheim Pharmaceuticals, Rigdefield, CT, USA
Initial NVP/nuc combination Rx has been proposed as a strategy to delay the

use of PI Rx. For PI sparing Rx to be useful, PIs must retain their effectiveness
after failure of NVP/nuc Rx. We examined PI in vitro susceptibility in highly NVP

Conclusions: In antiretroviral naive patients with >200 CD4 cells/mm3 and
a viral load between 4 and 5 loglo copies/ml, patients treated with d4T/ddl had
greater improvements in viral load (90% below 500 copies/ml) and CD4 counts
(+125 cells on average) at 24 weeks than patients treated by alternating d4T/ddl
and AZT/3TC or by AZT/3TC.

S12228I

HIV viral load response in subjects switched from
zidovudine (ZDV) - containing to stavudine
(D4T)-containing regimens in the Pacific Oaks Population
Study (POPS)

Mark Shaefer', W.D. Hardy:, L. Shaker-Irwin3, V. Williams2, C. Maude2,
J. Thommes3, N. Graham2. 'Glaxo Wellcome Inc., 5 Moore Drive, Research
Triangle Park, NC, 2Research Triangle Park, CA; 3Pacific Oaks Clinic, Beverly
Hills, CA, USA
Background: In the ACTG 290 study it was demonstrated that concomitant therapy with ZDV and D4T in ZDV experienced patients did not perform better than
D4T alone. There has also been a suggestion that patients treated with ZDV will
not respond well to subsequent treatment with D4T. We examined this hypothesis
by reviewing data from the prospective POPS cohort.
Objective: To determine HIV-1 RNA viral load and CD4 changes in subjects
that switch from ZDV-containing regimens to those containing D4T.
Methods: Patients are enrolled in an ongoing observational cohort study from
Pacific Oaks Medical Group. Data are available on the first 249 of 1000 enrolled subjects. Clinical, immunologic, and virologic data are collected quarterly.
In addition, retrospective data were collected by chart abstraction. HIV RNA
copy number was determined using Roche's Amplicor PCR assay. There were
41 subjects who entered the database on a ZDV-containing regimen and then
switched to a regimen containing D4T.
Results: At baseline, the overall cohort (n = 247) had a mean age of 42.8
years, were predominately male (97%), are Caucasian (76%), and 78% were
antiretroviral therapy experienced. The median CD4 count was 226 cells/mm3,
and the mean HIV RNA copy number (loglo copies/mL) was 3.5. Of the 41
patients who were treated with a ZDV-containing regimen and then switched to a
D4T-containing regimen. From a mean loglo HIV RNA of 4.1 at initiation of D4T,
the HIV RNA dropped to 3.2 after 26 weeks of follow-up (n = 21) and 2.7 after
40 weeks follow-up (n = 8). After 40 weeks of follow-up, 38% of patients had
undetectable (<400 copies/mL) HIV RNA levels. The median change in CD4 cell
count from initiation of D4T therapy was +67 cells.