HIV co-receptor tropism in treatment-naïve patients: impact on CD4 decline and subsequent response to HAART Laura Waters , Sundhiya Mandalia, Adrian Wildfire, Paul Randell, Brian Gazzard & Graeme Moyle. St Stephen’s Centre, Chelsea & Westminster Hospital, London, UK
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Laura Waters , Sundhiya Mandalia, Adrian Wildfire, Paul Randell, Brian Gazzard & Graeme Moyle.
HIV co-receptor tropism in treatment-naïve patients: impact on CD4 decline and subsequent response to HAART. Laura Waters , Sundhiya Mandalia, Adrian Wildfire, Paul Randell, Brian Gazzard & Graeme Moyle. St Stephen’s Centre , Chelsea & Westminster Hospital, London, UK. CCR5. I. Y. S. - PowerPoint PPT Presentation
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HIV co-receptor tropism in treatment-naïve patients: impact on CD4 decline and subsequent
response to HAART
Laura Waters, Sundhiya Mandalia, Adrian Wildfire, Paul Randell, Brian Gazzard &
Graeme Moyle.
St Stephen’s Centre, Chelsea & Westminster Hospital,
London, UK
R5 viruses (M-tropic, NSI)Transmitted variantsPrevalent in early disease
X4 viruses (T-tropic, SI)Late disease; associated with CD4 decline, HIV RNA increase and clinical progression
Dual-tropic viruses use CCR5 or CXCR4 (in vitro)
CCR5
Q
LSD
TF
F
LR
A
PI
A
L
HY
V
LV
W
L
FI
L
S
TV
L
A
LI
V
IV
V
Y
AS
L
YN
H
S
YVP
IF
L
A
GV
I
DT
F
L
VV
W
PL
I
A
ICI
IV
G
H
YI
L
GL
I
I
CI
S
LP
M
V
IL
T
F
YG
W
I
IV
F
IP
S
C
LT
A
YL
I
AGV
I
T
YP
I
I
GL
G
L
TS
F
F
NV
I
V
II
L
L
MGY
LN
F
C
AI
F
W
PY
C
L
TL
I
F
IA
L
G
GA
S
H
AKD
LKK M
TR S
D
FLCK
NY FG
DRYLAIV
N S RPRKLLA
KE
H T Q
VSEADD
RYI
CD
N DLWVVVFQFQ
FPY
R
SKLS
KLAKRKQHGKS
H
DSFILLEII KQGCE
FENT
HKV
LK
K
LFKTS
AQH
VSRGSS
A
TS
GIL S K
GKR
TESESSSF
GHSSVSHS S
VA
ANW
KNFNANEE
RF CPEKM
SDYDGSGME
ETYNDS T Y I S I GEM- NH2
*
*
*
N39-
-65 75-
-97 110-
-133 154-
-176 -202
224- -239
-262-282
308-
-352
F
A
CXCR4
352
C
LAD
TF
F
H
LL
S
PL
A
F
NY
I
VL
W
L
LF
I
G
FG
F
L
IL
I
LI
L
F
IT
F
YG
T
S
STV
LI
F
T
IT
V
GS
F
V
VV
W
PA
I
A
GCM
VL
L
I
YI
V
GL
V
L
SL
I
LP
I
V
TI
L
F
YV
W
L
MF
Y
IP
L
F
II
V
NA
L
LMV
I
F
YP
V
GL
G
L
S
L
F
NV
F
I
L
L
I
L I N
IN
F
C
TV
M
A
PY
C
V
TL
M
T
IA
I
G
EG
Q
H
EID
L
KR M
T
K S
Y
TMCQ
NF G
RYLAVV
A F A K ARTVTF
VG
HV L
SQKEG
LHYT
CS
Y SQ Y Q F
WKNFQ
H
PF
S
KTLL
V
HR
KKENRC
R
NTFQEFFG L
N N C SSSNR
DQ
L
CK
K
FFR N Y
L L V
HIAKRF
F
QK
ACC S I FQ Q
SVYTRST
G
EPERAS
EQ E
AA
AQ
AAI
QKV N
I K QC PESTYYNIDYI
PSS V
Q Y D M- NH2
- COOH
R31-
-57 67-
-89 102-
-125 146-
-168 -197
219- -235
-258
303-
TL
RA
I S V G L
R
P L
D
K
R
277-
DW
CCR5- & CXCR4-tropic HIV
Prevalence of Co-receptor UsageStudy/Source Population R5 X4 X4/R5
Maraviroc Phase 2a Naive 94 0 6
Homer cohortb
(n=979)Naive 83 <1 17
C & W cohortc
(n=563)Naïve/
Experienced85 <1 15
GSKd
(n=299)Naive 88 0 12
TORO 1/2e Experienced 62 4 34
ViroLogicf Experienced 50 2 48
a Data on file d Demarest et al. ICAAC 2004. Abstract H-1136b Brumme ZL et al. JID 2005;192(3):466-74. e Whitcomb et al. CROI 2003. Abstract 557c Moyle GJ et al. JID 2005;191(6):866-72 f Huang et al. ICAAC 2002. Abstract 2040
Prevalence and Predictive Factors for R5 and X4 Coreceptor Usage