1. 47th ICAAC
Chicago, USA, September 17–20, 2007
Efficacy and Safety of Maraviroc in Antiretroviral-Experienced Patients Infected With CCR5-Tropic HIV-1: 48-Week Results of MOTIVATE 1
J Lalezari1, J Goodrich2 , E DeJesus3, R Gulick4, H Lampiris5, M Saag6, N Bellos7, J Nadler8, P Tebas9, B Trottier10, M Wohlfeiler11, C Ridgeway12, M McHale12, E van der Ryst12, H Mayer2, on behalf of the MOTIVATE 1 Study Team
1Quest Clinical Research, UCSF, San Francisco, CA, USA
2Pfizer Global Research and Development, New London, CT, USA
3Orlando Immunology Center, Orlando, FL, USA
4Weill Medical College of Cornell University, New York, NY, USA
5San Francisco Veterans Affairs Medical Center, UCSF, San Francisco, CA, US
6University of Alabama at Birmingham, Birmingham, AL, USA
7Southwest Infectious Disease Associates, Dallas, TX, USA
8University of South Florida, Tampa, FL, USA
9University of Pennsylvania, Philadelphia, PA, USA
10Clinique Medicale L'Actuel, Montreal, QC, CANADA
11Wohlfeiler, Piperato & Associates, North Miami Beach, FL, USA
12Pfizer Global Research and Development, Sandwich, UK

2. Background
MOTIVATE 1 is one of two randomized, double-blind, placebo-controlled, Phase 3 studies investigating the safety and efficacy of the CCR5 antagonist maraviroc, in treatment-experienced patients with R5 HIV-1
In a planned interim analysis at 24 weeks1, maraviroc (QD and BID) + OBT vs OBT alone demonstrated
significantly greater virologic suppression rates
significantly greater increases in CD4+ count
no clinically relevant differences in safety profile
The MOTIVATE 1 primary efficacy endpoint is the change from baseline in HIV-1 RNA at 48 weeks
1. Lalezari J et al. 14th CROI 2007; Presentation 104bLB

3. MOTIVATE 1 Trial Design OBT* + placebo OBT* + maraviroc (150 mg† QD)
Randomization 1:2:2 N=601
OBT* + placebo
OBT* + maraviroc (150 mg† QD)
OBT* + maraviroc (150 mg† BID)
Screening (6 weeks)
24w
48w
Patient eligibility criteria:
R5 HIV-1 infection
HIV-1 RNA ≥5,000 copies/mL
Stable pre-study ARV regimen, or no ARVs for ≥ 4 weeks
Resistance to and/or ≥ 6 months’ experience with ≥ one ARV from three classes (≥ two for PIs)
Patients stratified by:
Enfuvirtide use in OBT
HIV-1 RNA < and ≥100,000 copies/mL at screening
* OBT = optimized background therapy of 3–6 ARVs (PK boosting doses of RTV not counted as an ARV)
† Patients receiving a PI (except TPV) and/or delavirdine in their OBT received 150 mg dose of MVC, all other patients received 300 mg dose of MVC

4. Demographics and Baseline Characteristics
Includes all patients who received at least one dose of study medication (full analysis set)
Treated N=585 §
OBT alone N=118
MVC QD + OBT N=232
MVC BID + OBT N=235
Mean age, yrs (range)
46 (31–71)
46 (19–75)
46 (25–69)
Male, n (%)
106 (90)
210 (91)
212 (90)
White, n (%)
99 (84)
187 (81)
197 (84)
Median CD4+ count*, cells/mm3 (range)
160 (1675)
168 (1812)
150 (2678)
Mean HIV-1 RNA*, log10 copies/mL (range)
(3.466.02)
(3.206.75)
(3.266.88)
Enfuvirtide in OBT, % 42 44 46
≤2 active drugs in OBT†, % 65 69 75
Tipranavir use in OBT, % 11 10
Darunavir use in OBT
Not Permitted
§ Two patients (1 MVC QD, 1 OBT alone) were assigned to the wrong treatment group due to a transcription error * Calculated for each patient as the mean of up to three pre-dose assessments (screening, randomization, and baseline) † According to overall susceptibility score
MOTIVATE 1-Week 48

5. Mean Change from Baseline in HIV-1 RNA
Includes all patients who received at least one dose of study medication
MVC QD + OBT (N=232)
MVC BID + OBT (N=235)
OBT alone (N=118)
Study week 24 48
from baseline (log10 copies/mL)
Mean change in HIV-1 RNA
Difference: -0.85* (97.5% CI: -1.22, -0.49)
Difference: -0.79* (97.5% CI: -1.14, -0.44)
Difference: -1.02* (97.5% CI: -1.39, -0.66)
Difference: -0.92* (97.5% CI: -1.28, -0.57)
HIV-1 RNA value imputed as baseline if patient discontinued before 48 weeks *Treatment difference vs OBT alone
MOTIVATE 1-Week 48

6. Percentage of Patients with Undetectable HIV-1 RNA
Includes all patients who received at least one dose of study medication Number of patients remaining on study treatment at Week 48: OBT alone, 27 (30%); MVC QD + OBT, 109 (60%); MVC BID + OBT, 127 (66%)
OBT alone (N=118)
MVC QD + OBT (N=232)
MVC BID + OBT (N=235)
<400 copies/mL
<50 copies/mL 10 20 30 40 50 60 70 80 90
100 10 20 30 40 50 60 70 80 90
100
60.4%*
57.5%*
48.5%*
46.8%*
Patients (%)
54.7%*
50.9%*
42.2%#
41.8%*
31.4%
24.6%
22.0%
16.1% 4 8 12 16 20 24 28 32 36 40 44 48 4 8 12 16 20 24 28 32 36 40 44 48
Time (weeks)
Time (weeks)
HIV-1 RNA value imputed as baseline if missing or if patient discontinued before 48 weeks *P< vs OBT alone #P< vs OBT alone
MOTIVATE 1-Week 48

7. Mean Change from Baseline in CD4+ Count
Includes all patients who received at least one dose of study medication
MVC QD + OBT (N=227)
MVC BID + OBT (N=233)
OBT alone (N=116)
Difference: +69 * (95% CI: +44, +93)
Difference: +59 * (95% CI: +35, +83)
Difference: +59 * (95% CI: +34, +84)
Difference: +55 * (95% CI: +30, +79)
Mean change from baseline in CD4+ count (cells/mm3) 24 48
Study week
Last observation carried forward * P< vs OBT alone
MOTIVATE 1-Week 48

8. Percentage of Patients With HIV-1 RNA <50 copies/mL at Week 48 According to Screening HIV-1 RNA*
Includes all patients who received at least one dose of study medication and had a post-baseline observation
MVC QD + OBT
MVC BID + OBT
OBT alone
<100,000 copies/mL
≥100,000 copies/mL
Total population
Patients (%)
N =
Last observation carried forward * Protocol-defined randomization stratum
MOTIVATE 1-Week 48

9. ENF experienced/ resistance ENF experienced/ resistance
MOTIVATE 1 and 2: Proportion of Patients Receiving ENF With Undetectable HIV-1 RNA at Week 48 According to ENF First Use
OBT alone
Maraviroc QD + OBT
Maraviroc BID + OBT
<400 copies/mL
<50 copies/mL
Patients (%) N=
ENF first use
ENF experienced/ resistance 91
108 59 30 75 72
ENF first use
ENF experienced/ resistance 91
108 59 30 75 72
MOTIVATE 1 & 2-Week 48
Last observation carried forward

10. Safety Analyses Unadjusted for Duration of Exposure
Includes all patients who received at least one dose of study medication
All causalities and severities
OBT alone N=118
MVC QD + OBT N=232
MVC BID + OBT N=235
Total exposure, patient-years 64
168
169
Patients with AEs
86%
90%
92%
Patients discontinuing due to AEs 6% 5%
Patients with grade 3 AEs
25%
17%
23%
Patients with grade 4 AEs 7% 9%
10%
Patients with SAEs
16%
14%
Patients with Category C events
Deaths* 1% 2%
AEs = adverse events; SAEs = serious adverse events *Includes deaths reported up to 28 days after stopping study drug No deaths were related to study drug according to the investigator
MOTIVATE 1-Week 48

11. Incidence of Adverse Events Occurring in ≥10% of Patients in Any Group, Unadjusted for Exposure
Includes all patients who received at least one dose of study medication
Total exposure in patient-years: OBT alone 64, MVC QD + OBT 168, MVC BID + OBT 169
OBT alone (N=118)
MVC QD + OBT (N=232)
MVC BID + OBT (N=235)
Patients (%)
MOTIVATE 1-Week 48
RTI = respiratory tract infection; ISR = injection site reaction

12. Number of Category C Events
Includes all patients who received at least one dose of study medication
Event, n
OBT alone N=118
MVC QD + OBT N=232
MVC BID + OBT N=235
Total exposure, patient-years 64
168
169
Cryptosporidial gastroenteritis 1
Cytomegalovirus infection*
Herpes simplex 2 5
Mycobacterium avium
Esophageal candidiasis 6
Pneumocystis jiroveci pneumonia
Pneumonia
Progressive multifocal leukoencephalopathy
Kaposi’s sarcoma
Lymphoma*
Total number of events Total number of patients, n (% )
6 6 patients (5.1%)
patients (4.7%)
patients (5.1%)
* Includes T-cell and diffuse large B-cell lymphomas
MOTIVATE 1-Week 48

13. Maximum Liver Function Test Values Over 48 Weeks Without Regard to Baseline
All causalities, n (%) Unadjusted for duration of exposure
OBT alone N=116*
MVC QD + OBT
N=228*
MVC BID + OBT N=234*
AST: Grade 3 (5–10 x ULN†) Grade 4 (>10 x ULN†)
4 (3.4) 0
7 (3.1) 3 (1.3)
7 (3.0) 4 (1.7)
ALT: Grade 3 (5–10 x ULN†) Grade 4 (>10 x ULN†)
2 (1.7) 0
11 (4.8) 1 (0.4)
5 (2.1) 3 (1.3)
Total bilirubin: Grade 3 (2.5–5 x ULN†) Grade 4 (>5 x ULN†)
4 (3.4) 2 (1.7)
17 (7.4) 2 (0.9)
10 (4.3) 2 (0.9)
* Total patients evaluated for each laboratory parameter † Upper limit of normal
MOTIVATE 1-Week 48

14. MOTIVATE 1 and 2: Change in CD4+ Cell Count from Baseline by Tropism Result at Time of Failure
Tropism result, Baseline → Treatment Failure
Mean change from baseline in CD4+ count in patients with treatment failure (cells/mm3 )
OBT alone N=271
MVC QD + OBT
N=477
MVC BID + OBT N=487
All treatment failures*
+24 (n=111)
+64 (n=92)
+74 (n=96)
R5 → R5
+25 (n=89)
+77 (n=33)
+133 (n=24)
R5 → D/M or X4
+61 (n=6)
+47 (n=35)
+57 (n=41)
* Includes patients with non-reportable/non-phenotypable tropism result at baseline and patients with non-reportable/non-phenotypable/missing tropism result at time of failure
MOTIVATE 1 & 2-Week 48

15. MOTIVATE 1: Summary of 48-Week Primary Analysis
Maraviroc (BID or QD) + OBT provided significantly greater virologic suppression rates and increases in CD4+ count compared to OBT alone at 48 weeks in this treatment-experienced population
No new or unique safety findings emerged
Adverse events, serious adverse events, and lab abnormalities (including grade 3/4 transaminase elevations) occurred with similar frequency between treatment groups
Category C (AIDS-defining events) were balanced across treatment groups
These results demonstrate that treatment with maraviroc + OBT provides sustained antiretroviral efficacy and tolerability in treatment- experienced patients

16. Acknowledgments Investigators and study site staff
Patients who participated in the study
Colleagues from Monogram Biosciences: J Whitcomb, E Coakley, C Petropoulos
R Harrigan, BC Centre for Excellence in HIV
Colleagues from Quintiles
Colleagues from Pfizer: S Felstead, A Bullivant, I Oborska, K George, M Westby, K Turner, D Lindell, D Paige, S Nuttall, J Merson, L Kapili, M Dunne