104aLB
Efficacy and Safety of Maraviroc plus Optimized Background Therapy in Viremic, ART-experienced Patients Infected with CCR5-tropic HIV-1 in Europe, Australia, and North America: 24-Week Results
M Nelson1, G Fätkenheuer2, I Konourina3, A Lazzarin4, N Clumeck5, A Horban6, M Tawadrous7, J Sullivan3, H Mayer7, and Elna van der Ryst*3
1Chelsea and Westminster Hosp, London, UK; 2Universitaetsklinik Köln, Germany; 3Pfizer Global R&D, Sandwich, UK; 4Hosp San Raffaele, Milan, Italy; 5Ctr Hosp Univ St Pierre, Brussels, Belgium; 6Szpital Zakazny Centrum Diagnostyki i Terapii AIDS, Warsaw, Poland; and 7Pfizer Global R&D, New London, CT, US
Background:
MOTIVATE 2 is 1 of 2 ongoing,
double-blind, placebo-controlled, phase 2b/3 studies assessing the safety and
efficacy of the novel CCR5 antagonist maraviroc (MVC), in treatment-experienced
HIV-infected patients. These are the results of a planned interim analysis at
week 24.
Methods:
Triple-class-experienced patients
(±triple-class resistance) with HIV-1 RNA
≥5000 copies/mL and only R5 virus (Trofile assay) were randomized 1 : 2 : 2 to receive placebo or MVC
(300-mg dose equivalent) once or twice daily plus optimized background therapy
(OBT) (3 to 6 ART drugs ± low-dose ritonavir). When OBT contained a protease
inhibitor (PI) (other than tipranavir) and/or delavirdine, MVC 150 mg once or twice daily was administered;
otherwise 300 mg once or twice daily was used. The primary endpoint was the
mean change in HIV-1 RNA from
baseline to week 24.
Results:
Of 475 patients randomized, 464
received ≥1 dose of study drug. Baseline† characteristics were
similar across treatment arms. Baseline median CD4 count (174, 174, and 182 cells/mm3) and mean HIV-1 RNA (4.89, 4.87, and 4.84 log10
copies/mL) were also similar in the placebo, MVC
once daily, and MVC twice daily arms, respectively. OBT contained ≤2
active drugs in 66.0, 62.6, and 62.3% of patients in the placebo, MVC once daily and MVC
twice daily arms, respectively. Adverse events, severe
adverse events, AIDS-defining events, and laboratory abnormalities (including
liver enzyme abnormalities) occurred with similar frequency in the 3 treatment
groups. The following analyses are based on
all randomized patients who received ≥1 dose of study drug:
|
|
Placebo+OBT
(n
= 91)
|
MVC Once Daily +
OBT
(n
= 182)
|
MVC Twice Daily +
OBT
(n
= 191)
|
|
Mean
change in viral load from baseline‡ (log10 copies/mL)
Treatment
difference –placebo (97.5%CI)
|
–0.93
N/A
|
–1.95
–1.02
(–1.43,
–0.62)
|
–1.97
–1.04
(–1.44,
–0.64)
|
|
%
<400 copies/mL
p value
vs placebo
|
23.1%
N/A
|
55.5%
<0.0001
|
61.3%
<0.0001
|
|
%
<50 copies/mL
p
value vs placebo
|
20.9%
N/A
|
45.6%
<0.0001
|
40.8%
0.0005
|
|
Mean
change in CD4 from baseline§ (cells/mm3)
p
value vs placebo (95%CI)
|
+64
(n = 90)
N/A
|
+112
(n = 180)
<0.001
(+22, +74)
|
+102
(n = 185)
<0.001
(+12, +64)
|
|
Category C AIDS-defining events, n
|
11
|
17
|
11
|
|
Discontinuations due to adverse events, n (%)
|
2
(2.2)
|
9
(4.9)
|
7
(3.7)
|
|
Deaths*,
n (%)
|
0
|
4
(2.2)
|
4
(2.1)
|
†Mean of all pre-dose assessments ‡Discontinuations=no change from BL
§Last Observation Carried Forward *No deaths were related to study drug according to investigators
Conclusions: In this
treatment-experienced population, MVC (twice or once daily) + OBT provided
significantly superior virologic control and increases in CD4 cell count
compared with placebo + OBT. There were no clinically relevant differences in
the safety profile between the MVC
(twice or once daily) + OBT and placebo + OBT treatment groups.
|
