Programme Supplement [International Conference on AIDS (16th: 2006: Toronto, Canada)]

Late Breaker Abstracts

Conclusion: A single dose of 5-40mg Fosalvudine Tidoxil
appears to be safe and well-tolerated. The AUC increases
with increasing doses, although non-proportionality cannot
be excluded due to the low number of patients. The terminal.' half-life of Fosalvudine Tidoxil is short compared to the dosing
i interval. Clinically relevant accumulation of the pro-drug is not
eypected during multiple dosing. A multiple dosing study will be
conducted.
TH LBO217
ACTG 5211: phase II study of the safety and efficacy
of vicriviroc in HIV-infected treatment-experienced
subjects
Gulick R.1, Su Z.2, Flexner C.3, Hughes M.2, Skolnik P.4, Godfrey
C. 5 61:,... ii s8" jec
S C., Greaves W.6, Wilkin T.1, Gross R.', Coakley E.8, Zolopa
A.9, Hirsch M., Kuritzkes D.1o, for the ACTG 5211 Study
Team. 'Cornell University, New York, United States, 2Harvard
vrf iv: School of Public Health, Boston, United States, 'Johns Hopkins
SUniversity Hospital, Baltimore, United States, 4Boston University
v...;:;. Medical Center, Boston, United States, sDivision of AIDS, NIH,
t<'" i Bethesda, United States, 6Schering-Plough Research Institute,
S Kenilworth, United States, 'University of PennsyTvania School of
Medicine, Philadelphia, United States, 5Monogram Biosciences,
u< Inc., South San Francisco, United States, 9Stanford University,
',<} i Palo Alto, United States, "oHarvard Medical School, Boston,
United States
Late Breaker Background: Vicriviroc is an investigational CCR5 inhibitor with
Abstracts potent short-term antiretroviral activity.
Methods: Double-blind, randomized, 48-week study of vicriviroc
in treatment-experienced patients taking ritonavir-containing
regimens with R5-tropic virus (Monogram assay) and HIV-1 RNA::. (VL) >5000 copies/mi. Vicriviroc at 5, 10, or 15 mg daily (or
placebo) was given for 14 days; then background antiretrovirals
were optimized. Virologic failure was defined as confirmed VL
<1 log10 copies/ml below baseline at/after week 16; post-failure
cross-over to vicriviroc was permitted. Primary endpoint was
change in VL at day 14. The 5 mg dose was discontinued early
following recommendation from the Study Monitoring Committee
E' and the study was unblinded following reports of 5 malignancies.
Data for blinded study period are presented; open-label follow-up
continues.
Results: 118 patients were randomized (8% women; 34% nonwhites) with median VL 36380 (4.56 Iog10) copies/ml and CD4 146

THLBO218
TNX-355, in combination with optimized background
regimen (OBR), achieves statistically significant viral load
reduction and CD4 cell count increase when compared with
OBR alone in phase 2 study at 48 Weeks
D. Norris1, J. Morales2, E. Godofsky3, F. Garcia4, R. Hardwicke0, S.
Lewis'. 'Comprehensive Research Center, Tampa, United States,
2Clinical Research Puerto Rico Inc., San Juan, Puerto Rico, 'Bach
& Godofsky, Bradenton, United States, 'Valley AIDS Council,
Harlingen, United States, 'University of Texas Health Science
Center, Houston, United States, 6Tanox, Inc., Clinical Development,
Houston, United States
Background: TNX-355 is a novel humanized monoclonal antibody
that binds to domain 2 of the CD4 receptor, blocking entry of HIV-1
into target cells. A 48-week randomized, double-blind, placebocontrolled study assessed the safety and efficacy of two dosage
regimens of TNX-355 plus OBR versus (vs.) placebo plus OBR.
The primary endpoint was mean change in HIV-1 RNA (VL) from
baseline (BL) at Week 24; additional assessments of safety and
efficacy were conducted through Week 48.
Methods: Triple-class experienced HIV-infected patients were
randomized to receive TNX-355 intravenously: 10mg/kg Q wk for
9 doses followed by 10mg/kg Q 2 wks; 15 mg/kg Q 2 wks, or
placebo. All patients received OBR. After virologic failure (< 0.5
logo drop from BL after week 16), patients received 15 mg/kg
open-label TNX-355 Q 2 wks in combination with new OBR. An
analysis of the intent-to-treat population was performed, along
with statistical tests for immunologic and virologic measurements
at 24 and 48-weeks, corrected for multiple comparisons of each
TNX-355 arm vs. the placebo arm.
Results: 82 patients (87% male, 46% white) enrolled: mean age
46 years. Summary of Week 48 Data:

I
I

TNX-355
Mean VL change
log,*
N (%/) 1.0 log1
reduction
N (%) >0.5 log1o
reduction
% <400 (%<50)
copies/mL
Median time
loss of virologic
response (days)
Mean change in
CD4+ (cells/mL)

S15mg/kg+OBR 10mg/kg+OBR Placebo+OBR
n=28 n=27 n=27
-0.71 (p=0.009) -0.96 (p<0.001) -0.14

9 (32)

10 (37)

3 (11)

11 (39) (p=0.029) 12 (44) (p=O.014) 3 (11)

7(4)

4 (0)

0 (0)

11 IUCA '

cells/uL.

253 (p=0.003) 230 (p=0.003) 0
51 (p=0.016) 48 (p=0.031) I

vicriviroc dose
N
median length of study
treatment (weeks)
discontinued early (n, %)
mean HIV-1 RNA change
(logo copies/mi) at day 14
mean HIV-1 RNA change
(logl0 copies/ml) at week 24
mean CD4 cell count change
(/uL) at week 24
co-receptor change (R5 to
D/M or X4) (n, %)

5 mg 10 mg 15 mg placebo
30 30 30 28
24 41 43 25

9 (30%) 8 (27%) 6 (20%)

22 (79%)
+0.06

-0.87
-1.51
+84

-1.15 -0.92

-1.86 -1.68 -0.29
+142 +142 -9

8 (27%) 3 (10%) 2 (7%)

1 (4%)

*Non-completer=mean of last two values
Conclusions: TNX-355 in combination with OBR resulted
in a statistically significant difference in viral load reduction
compared to placebo plus OBR at Week 48. Treatment with TNX355 is associated with durable viral load reductions and clinically
meaningful increases in CD4 counts in treatment-experienced
patients.
Track C
THLB0101
Low levels of pre-exposure prophylaxis awareness and
use among HIV-negative/unknown gay/bisexual men: San
Francisco Bay Area residents, circuit party attendees, and
clients of an urban STD clinic
A. Liu', S. Wheeler1, E. Vittinghoff2, H.F. Raymond, K. Ahrens',
J. Klausner', S. Buchbinder'. 'San Francisco Department of Public
Health, San Francisco, United States, 2University of California, San
Francisco, San Francisco, United States

HIV-1 RNA decrease was greater in each vicriviroc group than
placebo at day 14 and week 24 (P<.01) and not different between
vicriviroc groups (P>.05)(ITT). Grade 3/4 adverse events were
similar across groups. Among vicriviroc patients, 2 developed
Hodgkin's disease (HD)(one with prior HD); 2 non-Hodgkin's
lymphoma (one with prior HD); and 1 gastric adenocarcinoma.
Conclusions: In treatment-experienced patients, vicriviroc
demonstrated potent 14-day virologic suppression and, following
optimization of background antiretrovirals, sustained antiretroviral
activity over 24 weeks. The relationship of vicriviroc to malignancy
is uncertain.

XVI INTERNATIONAL AIDS CONFERENCE * 13-18 AUGUST 2006 * TORONTO CANADA * PROGRAMME SUPPLEMENT