Transcript 40 to

44th ICAAC
ANTIRETROVIRAL TREATMENT HIGHLIGHTS
An HIV/AIDS Overview from the
44th Annual Interscience Conference on
Antimicrobial Agents and Chemotherapy
October 30 - November 2, 2004; Washington, DC
Summarized by
Douglas J. Ward, MD, FACP
Dupont Circle Physicians Group, Washington, DC
Supported by an unrestricted educational grant from
44thICAAC
ANTIRETROVIRAL TREATMENT HIGHLIGHTS
New Findings on:
 Virologic Monitoring and Drug Resistance
 Nucleoside/Nucleotide Reverse Transcriptase Inhibitor
Options and Regimens for First- and Second-line Therapy
 Simplification/Switch Strategies for Patients With Virologic
Suppression
 Current and Investigational Protease Inhibitors in First- and
Second-line Therapy
 CCR5 Antagonists and Viral Tropism
Virologic Monitoring and Drug Resistance
44thICAAC
Intermittent Low-Level HIV-1 Viremia (“Blips”) in
Virologically Controlled Patients
Viremic “blips” during antiretroviral therapy do not appear to result in evolution of resistant virus or
virologic failure.
 10 patients with HIV-1 RNA < 50 copies/mL for 11-79 months
• Viral loads measured 3 times weekly for 3-4 months
• Each test read by 2 independent labs
 18 blips detected in 9 patients
• Only 1 confirmed by both labs
 No significant genotypic changes detected
 No correlation found with any demographic, clinical, or treatmentrelated factor
Viremic blips are common, do not predict treatment failure or
development of resistance, and likely represent laboratory variation
in the majority of cases.
Nettles RE, et al. 44th ICAAC, 2004. Abstract H-1134.
www.medscape.com/hiv-aidshome
44thICAAC
Frequency and Characteristics of the NRTI-Associated
K65R and L74V/I RT Mutations
Frequency of NRTI-Associated Mutations in 2003 (ViroLogic Database)
M184V/I
44%
31%
T215Y/F
M41L
25%
20%
D67N
20%
K219Q/E/N/R
16%
K70R
15%
L210W
12%
L74V/I
4%
K65R
2%
Y115F
Q151M
1%
T69 ins
1%
0
5
10
15
20
25
30
35
40
45
50
% Genotypes (n > 16,000)
McColl DJ, et al. 44th ICAAC, 2004. Poster H-178.
www.medscape.com/hiv-aidshome
44thICAAC
Frequency and Characteristics of the NRTI-Associated
K65R and L74V/I RT Mutations
Phenotypic NRTI Resistance of HIV-1 Variants With K65R
96
100
% Above Cut-off
85
96
83
80
71
62
60
40
29
20
0
100
99
97
2 0 6
ZDV
(1.9)
13
22
13
0
d4T
(1.7)
1
TDF
(1.4)
ABC
(4.5)
ddl
(1.7)
3TC
(3.5)
NRTIs (PhenoSense cut-off)
K65R alone
McColl DJ, et al. 44th ICAAC, 2004. Poster H-178.
K65R + M184V
K65R + NAMs
www.medscape.com/hiv-aidshome
44thICAAC
Frequency and Characteristics of the NRTIAssociated K65R and L74V/I RT Mutations
Phenotypic NRTI Resistance of HIV-1 Variants With L74V/I
100
% Above Cut-off
92
85
85
100
79
80
63
57
60
55
40
36
29
20
0
0 0
0 0
ZDV
(1.9)
0 0
d4T
(1.7)
TDF
(1.4)
3
0
ABC
(4.5)
ddl
(1.7)
3TC
(3.5)
NRTIs (PhenoSense cut-off)
L74V/I alone
McColl DJ, et al. 44th ICAAC, 2004. Poster H-178.
L74V/I + M184V
L74V/I + NAMs
www.medscape.com/hiv-aidshome
44thICAAC
Predictors of K65R With Tenofovir in Antiretroviral
Therapy (ART)-Experienced and -Naive Patients
In patients taking tenofovir, emergence of the K65R drug resistance mutation was associated with the
absence or presence of other specific regimen components.
 258 ART-experienced and 37 ART-naive patients
• median follow-up, 67 weeks
 K65R developed in 29 (11%) ART-experienced persons
• 28 had virologic failure
• No K65R in ART-naive persons
 Taking triple-NRTI regimens including tenofovir increased risk of
K65R
• Tenofovir/didanosine + lamivudine or emtricitabine
• Tenofovir/abacavir + lamivudine or emtricitabine
 Taking tenofovir with zidovudine or lamivudine reduced risk of K65R
Staszewski S, et al. 44th ICAAC, 2004. Poster H-177.
www.medscape.com/hiv-aidshome
44thICAAC
Prevalence of Transmitted HIV Drug Resistance in ARTNaive Individuals in the United States in 2003
Proportion of Patients With Reduced Susceptibility to > 1 Drug (N = 317)
23%
Any ARV
0.9%
> 1 NRTI
18%
> 1 NNRTI
10%
1 NNRTI
3%
2 NNRTI
3 NNRTI
6%
> 1 PI
6%
NRTI mutations: 15%
 V118I (4%), D67N (1%), M41L (or mix, 1%)
NNRTI mutations: 6%
 K103N (3%), G190A (or mix, 1%), V108I (or mix, 1%)
4%
1 PI
2 PI
Primary PI mutations: 4%
 None > 1%
0.9%
0.3%
3 PI
0
5
10
15
20
25
% Subjects
Ross LL, et al. 44th ICAAC, 2004. Poster H-173.
www.medscape.com/hiv-aidshome
Nucleoside/Nucleotide Reverse
Transcriptase Inhibitor
Options and Regimens
for First- and Second-line Therapy
44thICAAC
Trizivir + Tenofovir vs Combivir + Efavirenz
in ART-Naive Patients
A single-class, quadruple-NRTI regimen was shown to be equivalent to a standard, 2-class efavirenzbased regimen for first-line therapy.
TIMS: 48-week randomized, open-label trial
 113 ART-naive subjects were randomized to receive:
Quad-NRTI (n=57)
ZDV/3TC/ABC 300/150/300 mg BID
+ TDF 300 mg QD
Triple (n=56)
or
ZDV/3TC 300/150 mg BID +
Efavirenz 600 mg QD
 Baseline characteristics were comparable, including:
Median HIV RNA (log10 copies/mL)
5.26
5.13
Median CD4+ (cells/mcL)
194
153
Moyle G, et al. 44th ICAAC, 2004. Abstract H-1131.
www.medscape.com/hiv-aidshome
44thICAAC
Trizivir + Tenofovir vs Combivir + Efavirenz
in ART-Naive Patients
Proportion of Subjects With HIV-1 RNA <50 Copies/mL Through Week 48 (ITT, M=F)
100
% Subjects
80
68 %
67 %
60
40
EFV+ZDV/3TC
Quad-NRTI
20
0
0
4
8
12
24
36
48
Treatment Time (Weeks)
 1 virologic failure (Quad-NRTI)
 Total cholesterol decreased
significantly in Quad-NRTI arm: -0.2
mmol/L vs +0.8 mmol/L (P <.001)
ITT , intention-to-treat analysis; M=F, missing equals failure
Moyle G, et al. 44th ICAAC, 2004. Abstract H-1131.
www.medscape.com/hiv-aidshome
44thICAAC
Trizivir + Tenofovir in ART-Naive Subjects: COL40263
Proportion of Subjects With HIV-1 RNA <50 Copies/mL
at Week 24
100
60
 12 (9.8%) due to adverse events
85
80
71
 27 subjects (22%) discontinued
study
65
61
54
46
40
 9 (8%) had grade 3/4 lab
abnormalities
 8 (7%) had suspected ABC
hypersensitivity
20
0
Overall
BL VL
<100,000
ITT M=F
BL VL
> 100,000
 Reductions in lipids were
observed
 8 virologic nonresponders
AT
• >1 TAMs only, 3
No of Subjects
Overall
<100,000
>100,000
• >1 TAMs+M184V, 3
ITT M=F
123
52
71
• Wild-type, 2
AT
94
40
54
ITT, intention-to-treat analysis; M=F, missing equals failure; AT, as treated
DeJesus E, et al. 44th ICAAC, 2004. Poster H-564.
www.medscape.com/hiv-aidshome
44thICAAC
Trizivir + Tenofovir in Patients With Early Virologic
Failure on Initial Regimen: ESS30005
Zidovudine/lamivudine/abacavir (Trizivir) + tenofovir may be a viable rescue option for patients with early
virologic failure on a standard initial regimen.
ESS30005: Open-label study
 51 patients with early virologic failure (VL >400 but <10,000 copies/mL)
• Failing regimens: zidovudine (or stavudine)/lamivudine + PI or NNRTI
 Baseline characteristics:
• Median HIV-1 RNA: 3.3 log10 copies/mL (68% <5000 copies/mL)
• Median CD4+ cell count: 436 cells/mcL (37% > 350 cells/mcL)
• < 2 NRTI mutations: M184V (82%), TAMs (24%), no K65R
 43 patients (84%) completed > 24 weeks of follow-up
Rodriguez AE, et al. 44th ICAAC, 2004. Poster H-563.
www.medscape.com/hiv-aidshome
44thICAAC
Trizivir + Tenofovir in Patients With Early Virologic
Failure on Initial Regimen: ESS30005
Proportion of Subjects With HIV-1 RNA <50 Copies/mL Through Week 24
100
93%
80%
75%
65%
% Subjects
80
60
40
20
0
0
4
8
12
16
20
24
Treatment Time (Weeks)
Obs <400
Obs <50
ITT M=F <400
ITT M=F <50
ITT, intention-to-treat analysis; M=F, missing equals failure; Obs, observed analysis
Rodriguez AE, et al. 44th ICAAC, 2004. Poster H-563.
www.medscape.com/hiv-aidshome
44thICAAC
Tenofovir/Emtricitabine + Efavirenz vs Combivir +
Efavirenz in ART-Naive Patients
Better overall responses were seen with tenofovir/emtricitabine than with zidovudine/lamivudine
(Combivir) in the preliminary analysis of this head-to-head study.
Study 934: Open-label, randomized, noninferiority study
 Planned 24-week analysis (96-week study)
 ART-naive patients were randomized to receive:
Tenofovir/Emtricitabine (n=255)
TDF 300 mg + FTC 200 mg
+ EFV (all QD)
or
Combivir (n=254)
ZDV/3TC 300/150 mg (BID)
+ EFV (QD)
 Baseline characteristics were comparable, including:
Median HIV RNA (log10 copies/mL)
% HIV RNA > 100,000
Median CD4+ (cells/mcL)
% < 200
Gazzard B, et al. 44th ICAAC, 2004. Abstract H-1137c.
5.0
5.0
52
50
233
241
42
41
www.medscape.com/hiv-aidshome
44thICAAC
Tenofovir/Emtricitabine + Efavirenz vs Combivir +
Efavirenz in ART-Naive Patients
Time to Loss of Virologic Response (TLOVR) <50 Copies/mL (ITT)
100
P = .038
80
73%
65%
60
40
20
0
0
4
8
16
24
Treatment Time (Weeks)
TDF/FTC
ZDV/3TC
ITT, intention-to-treat analysis
Gazzard B, et al. 44th ICAAC, 2004. Abstract H-1137c.
www.medscape.com/hiv-aidshome
44thICAAC
Tenofovir/Emtricitabine + Efavirenz vs Combivir +
Efavirenz in ART-Naive Patients
Patient Disposition Through Week 24
TDF/FTC
ZDV/3TC
11
21*
Adverse Event (%)
3
9†
Noncompliance/Lost Follow-up (%)
4
6
Suboptimal Virologic Response (%)
2
1
Other (%)
3
5
Permanent Study Regimen
Discontinuation (%)
* P = .003
†P
= .008
 5% (vs 0% ) discontinued due to anemia in the Combivir arm
Significantly better overall response with tenofovir/emtricitabine due
to fewer adverse events leading to fewer discontinuations in that arm
Gazzard B, et al. 44th ICAAC, 2004. Abstract H-1137c.
www.medscape.com/hiv-aidshome
Efficacy of Fixed-Dose Abacavir/Lamivudine +
Efavirenz: ESS30009
44thICAAC
Proportion of Subjects With HIV-1 RNA <50 Through Week 24 (ITT, M=F)
% Subjects
100
80
69%
60
40
ABC/3TC+EFV
20
ABC/3TC+TDF
Terminated
0
0
4
8
12
16
20
24
Treatment Time (Weeks)
 Abacavir/lamivudine + tenofovir stopped due to a 49% failure rate
• Patients in that arm were assigned new regimens and followed
– ABC/3TC/EFV (35%), ABC/3TC/TDF/ZDV (15%), ZDV/3TC/EFV (11%),
ABC/3TC/ZDV/EFV (9%), TDF/3TC/ZDV/EFV (5%)
ITT, intention-to-treat analysis; M=F, missing equals failure
Gallant JE, et al. 44th ICAAC, 2004. Poster H-567.
www.medscape.com/hiv-aidshome
44thICAAC
Efficacy of Subsequent Treatment of Tenofovir +
Abacavir/Lamivudine Nonresponders: ESS30009
Virologic Response Following Switch to Second-line Regimens up to 12 Weeks
100
80
60
40
20
Obs <400
Obs <50
ITT M=F <400
ITT M=F <50
0
2
4
8
12
Treatment Time Post Switch (Weeks)
 Predictors of a 12-week post-switch viral load < 50 copies/mL:
• Baseline viral load: OR, 0.163; P = .001
• Efavirenz use: OR, 5.797; P = .015
• Abacavir use: OR, 7.731; P = .009
• Zidovudine use: OR, 5.032; P = .022
ITT, intention-to-treat analysis; M=F, missing equals failure; Obs, observed
Gallant JE, et al. 44th ICAAC, 2004. Poster H-567.
www.medscape.com/hiv-aidshome
44thICAAC
Early Virologic Failure With Once-Daily
Didanosine/Tenofovir/Efavirenz in ART-Naive Patients
Didanosine/tenofovir/efavirenz, but not didanosine/lamivudine/efavirenz, was associated with poor
virologic responses in patients with high viral loads and low CD4+ cell counts.
 In an open-label trial, ART-naive individuals were randomized to receive:
• QD didanosine/tenofovir/efavirenz (n=41)
• QD didanosine/lamivudine/efavirenz (n=36)
 The study was terminated after an unplanned analysis at week 12
ddI/TDF/EFV
ddI/3TC/EFV
n (%) with VL <50 copies/mL at week 12
22 of 36 (61%)
24 of 34 (71%)
n (%) with virologic failure through week 12
5 of 41 (12%)
0 of 36 (0%)*
*P < .05
 Drug-resistant virus emerged rapidly in first 4 virologic failures
 All 5 subjects with virologic failure had baseline VL >100,000
copies/mL and CD4+ cell count < 200 cells/mcL
Moyle G, et al. 44th ICAAC, 2004. Poster H-566.
www.medscape.com/hiv-aidshome
44thICAAC
Tenofovir/Didanosine: Paradoxical CD4+ Cell Declines
Despite Good Virologic Control
The combined use of tenofovir + didanosine can cause CD4+ cell counts to fall, even as viral load goes
down or remains undetectable.
Retrospective assessment: 570 patients were taking TDF/ddI, TDF,
ddI, or neither agent
 All subjects had HIV RNA <400 copies/mL for >1 year (N=570)
 Paradoxical CD4+ cell decreases seen only with TDF/ddI
• not observed with TDF or ddI individually or with other NRTI
 CD4+ cell decreases were more common in patients:
• who switched to TDF/ddI to simplify regimen
• on NRTI-only regimens that included TDF/ddI
• with longer exposure to higher doses of ddI
 Median CD4+ cell decline of 385 cells/mcL among subjects who
switched to a triple-NRTI regimen containing TDF/ddI
 CD4+ cell decreases appeared after ~6 months of TDF/ddI and then
increased in magnitude
Barrios A, et al. 44th ICAAC, 2004. Abstract H-1132.
www.medscape.com/hiv-aidshome
Simplification/Switch Strategies for Patients
With Virologic Suppression
44thICAAC
Switching From a PI- to a Once-Daily EfavirenzBased Regimen: VEST-QD
Once-daily efavirenz + didanosine/lamivudine appears to be a safe and effective option for virologically
suppressed patients switching from a PI-based regimen.
VEST-QD: Interim results of an ongoing 48-week open-label trial
 Patients with VL <50 copies/mL on PI regimens were randomized to:
• Efavirenz + didanosine/lamivudine (all QD)
• Efavirenz + current NRTIs (ZDV/3TC, 51%; d4T/3TC, 30%; other, 19%)
Virologic Response at Week 24 (ITT NC=F):
ddI/3TC (n=92)
Current NRTI (n=94)
HIV RNA <400 copies/mL (%)
89
90
HIV RNA <50 copies/mL (%)
85
87
 1 virologic failure (current-NRTI arm)
 HDL-C levels increased in both arms (P < .0001)
 Adherence improved in both arms (P < .05)
• No difference between arms
ITT, intention-to-treat analysis; NC=F, noncompletion equals failure
Cohen C, et al. 44th ICAAC, 2004. Poster H-577.
www.medscape.com/hiv-aidshome
44thICAAC
Trizivir vs Combivir + Nevirapine in Patients With
Virologic Suppression: SimplifiHAART
Two PI-sparing simplification strategies for patients with virologic suppression appear to be comparably
safe and effective, and associated with improvements in cholesterol levels.
SimplifiHAART: 48-week randomized, open-label switch study
 134 patients with undetectable VL (not defined) for > 24 months
were randomized to:
•
zidovudine/lamivudine/abacavir
•
zidovudine/lamivudine + nevirapine
 ~90% were taking a PI-based regimen at baseline
Results through week 48
 13 (19%) and 14 (21%) subjects discontinued due to side effects
 1 virologic failure in each arm
ZDV/3TC/ABC (n=68)
ZDV/3TC/NVP (n=66)
71
73
98.6
98.5
% Undetectable VL (ITT NC=F)
% Undetectable VL (OT)
ITT, intention-to-treat analysis; NC=F, noncompletion equals failure
Bonjoch A, et al. 44th ICAAC, 2004. Poster H-562.
www.medscape.com/hiv-aidshome
44thICAAC
Trizivir vs Combivir + Nevirapine in Patients With
Virologic Suppression: SimplifiHAART
Proportion of Patients with Elevated TC and LDL-C Levels at Baseline and Week 48
Baseline
Week 48
P
TC >5.2 mmol/L - Trizivir (%)
55.6
30.5
.019
LDL-C TC >3.36 mmol/L - Trizivir (%)
60.0
20.6
.003
TC >5.2 mmol/L - Combivir/nevirapine (%)
68.9
42.2
.019
LDL-C >3.36 mmol/L - Combivir/nevirapine (%)
59.3
41.7
NS
Bonjoch A, et al. 44th ICAAC, 2004. Poster H-562.
www.medscape.com/hiv-aidshome
44thICAAC
Favorable Lipid Changes With Switch From Stavudine to
Tenofovir: GS903E
Mean Changes in Fasting Lipid Parameters After d4T to TDF Switch
Mean Change (mg/dL)
0
TC
LDL-C
-10
LDL-C/HDL-C
-6* -4*
-20
TG
-0.2 -0.2
Week 12
(n=85)
-17*
-23*
-30
-40
HDL-C
*P < .001
Week 24
(n=83)
-40* -38*
-44*
-50
-60
-70
-62*
 85 patients substituted tenofovir for stavudine in rollover phase of GS903
 No patient lost viral suppression (<50 copies/mL) through 24 weeks post-switch
 No patient discontinued due to adverse events
Suleiman JMAH, et al. 44th ICAAC, 2004. Poster H-158.
www.medscape.com/hiv-aidshome
Current and Investigational Protease Inhibitors
Favorable Increases in HDL-Cholesterol With
Fosamprenavir in ART-Naive Patients: NEAT
44thICAAC
In the NEAT study, treatment with unboosted fosamprenavir + abacavir/lamivudine was associated with
increases in high-density lipoprotein cholesterol (HDL-C) levels.
Secondary analysis of the 48-week NEAT study
 Randomized, open-label study in ART-naive patients, comparing:
• fosamprenavir 1400 mg + abacavir 300 mg/lamivudine 150 mg (n=166)
• nelfinavir 1250 mg + abacavir 300 mg/lamivudine 150 mg (n=83)
 Baseline lipids were similar, with relatively low HDL-C, in both arms
 HDL-C and other lipid changes were observed through week 48:
Mean Change From Baseline at Week 48
Fosamprenavir
Nelfinavir
-1
+12
HDL-C (%)
+37
+22
TC/HDL-C ratio (%)
+31
+29
Triglycerides (mg/dL)
+2
+46
Total cholesterol (TC) (%)
Nadler JP, et al. 44th ICAAC, 2004. Poster H-156.
www.medscape.com/hiv-aidshome
44thICAAC
Favorable Increases in HDL-Cholesterol With
Fosamprenavir in ART-Naive Patients in the NEAT Study
Increases in HDL-C to Maximum Post Baseline by NCEP Lipid Category
Fosamprenavir (n=148)
Nelfinavir (n=72)
100%
% Subjects
80%
10
27
27
21
<40 mg/dL
43
60%
>40 to <60 mg/dL
49
40%
76
69
>60 mg/dL
47
20%
24
0%
BL
Max. postBL
Nadler JP, et al. 44th ICAAC, 2004. Poster H-156.
BL
Max. postBL
www.medscape.com/hiv-aidshome
44thICAAC
Tipranavir/Ritonavir vs Other Boosted PIs in ARTExperienced Patients: RESIST-1
Following 24 weeks of treatment, tipranavir/ritonavir appeared to be superior to other boosted PIs in
patients with PI-resistant virus.
RESIST-1: Randomized, controlled, open-label, phase 3 trial
 Study participants had multiple PI experience and PI-resistant virus
• failing a PI-containing regimen at entry
•  1 primary PI mutation
•  2 mutations at codon 33, 82, 84, or 90
 620 patients were randomized to receive:
Tipranavir (n=311)
Tipranavir/ritonavir 500/200 mg +
optimized background regimen
Comparator PI (n=309)
or
Comparator PI/ritonavir + optimized
background regimen
 36.1% of subjects received enfuvirtide
Hicks C, et al. 44th ICAAC, 2004. Abstract H-1137a.
www.medscape.com/hiv-aidshome
44thICAAC
Tipranavir/Ritonavir vs Other Boosted PIs in ARTExperienced Patients: RESIST-1
Discontinuations and Adverse Events
 More people discontinued a control PI than tipranavir, usually
because of virologic failure:
Tipranavir (n=311)
Comparator PI (n=309)
On treatment
263
151
Discontinued
• Virologic failure
• Adverse events
48
13
25
139
109
9
 Rates of grade 3/4 side effects were similar overall (22.8% and 18.1%)
but differed significantly for certain parameters:
ALT elevation (%)
6.9
1.3 *
Cholesterol (%)
4.2
0*
Triglycerides (%)
21.7
12.5†
* P < .001
Hicks C, et al. 44th ICAAC, 2004. Abstract H-1137a.
†P
< .01
www.medscape.com/hiv-aidshome
44thICAAC
Tipranavir/Ritonavir vs Other Boosted PIs in ARTExperienced Patients: RESIST-1
Virologic Responses at 24 Weeks (ITT, LOCF)
60
*P < .001
40
34.7 *
25.1 *
*P < .001
16.5 *
20
10*
0
Tipranavir
< 400 copies/mL
Comparator PI
< 50 copies/mL
ITT, intention-to-treat analysis; LOCF, last observation carried forward
Hicks C, et al. 44th ICAAC, 2004. Abstract H-1137a.
www.medscape.com/hiv-aidshome
44thICAAC
Tipranavir/Ritonavir vs Other Boosted PIs in ARTExperienced Patients: RESIST-1
Impact of Enfuvirtide (ENF) on Virologic Responses (ITT, LOCF)
< 400 copies/mL
% Subjects
60
40
47.1*
< 50 copies/mL
*P < .001
32.8*
34.7
21.9*
25.1
14.3*
16.5
20
10.0
0
All
+ENF
All
+ENF
Tipranavir/r
All
+ENF
All
+ENF
Comparator PI
ITT, intention-to-treat analysis; LOCF, last observation carried forward
Hicks C, et al. 44th ICAAC, 2004. Abstract H-1137a.
www.medscape.com/hiv-aidshome
CCR5 Antagonists and Viral Tropism
44thICAAC
873140, a Novel CCR5 Antagonist: 10-Day Responses to
Monotherapy
HIV-1 RNA (log10 copies/mL)
Median Change in Viral Load at Day 10 by Dose Group
Placebo
(n=9)
0
-0.2
-0.4
-0.6
-0.8
-1
-1.2
-1.4
-1.6
-1.8
200 QD
(n=7)
200 BID
(n=8)
400 QD
(n=8)
600 BID
(n=8)
-0.12
-0.46
-1.03
-1.23
-1.66
 21 ART-experienced, 19 ART-naive subjects
 HIV RNA >5000 copies/mL, CD4+ >200 cells/mcL, CCR5-tropic virus at baseline
 No serious adverse events in any treatment group
Lalezari J, et al. 44th ICAAC, 2004. Abstract H-1137b.
www.medscape.com/hiv-aidshome
44thICAAC
Distribution of Coreceptor Tropism According to
Treatment Status
Relative Distribution of HIV-1 Tropism Among ART-Naive and -Experienced Patients*
100
82
% Samples
80
88
Total
ART-Naive
ART-Experienced
67
60
40
20
28
16 12
2
0
R5
n = 339 263 76
R5/X4
36 67 31
5
0
X4
6
6
Tropism
* Source = 442 stored samples from GlaxoSmithKline clinical trials;
412 were successfully typed
Demarest J, et al. 44th ICAAC, 2004. Abstract H-1136.
www.medscape.com/hiv-aidshome
44thICAAC
Distribution of Coreceptor Tropism According to CD4+
Cell Count
Prevalence of R4- or R5/X4-Tropic Isolates by Absolute CD4+ Cell Count*
% X4 or R5/X4
80
60
41.9
40
40
20
16
16
14.8
0
> 300
(n=248)
> 201-300 > 101-200 > 51-100
(n=104)
(n=81)
(n=31)
< 50
(n=50)
CD4+ cell count (cells/mcL)
* Source = 865 stored samples from Chelsea and Westminster Hospital, London;
616 were successfully typed
Moyle G, et al. 44th ICAAC, 2004. Abstract H-1135.
www.medscape.com/hiv-aidshome