Supported by an unrestricted educational grant from
ANTIRETROVIRAL TREATMENT HIGHLIGHTS
Summarized by
Douglas J. Ward, MD, FACPDupont Circle Physicians Group, Washington, DC
An HIV/AIDS Overview from the
44th Annual Interscience Conference onAntimicrobial Agents and Chemotherapy
October 30 - November 2, 2004; Washington, DC
44th ICAAC
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
ANTIRETROVIRAL TREATMENT HIGHLIGHTS44thICAAC
Virologic Monitoring and Drug Resistance
44thICAAC
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Intermittent Low-Level HIV-1 Viremia (“Blips”) in Virologically Controlled Patients
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 treatment-related factor Viremic blips are common, do not predict treatment failure or
development of resistance, and likely represent laboratory variation in the majority of cases.
Viremic “blips” during antiretroviral therapy do not appear to result in evolution of resistant virus or virologic failure.
Nettles RE, et al. 44th ICAAC, 2004. Abstract H-1134.
44thICAAC
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Frequency of NRTI-Associated Mutations in 2003 (ViroLogic Database)
% Genotypes (n > 16,000)
Frequency and Characteristics of the NRTI-Associated K65R and L74V/I RT Mutations
McColl DJ, et al. 44th ICAAC, 2004. Poster H-178.
0 5 10 15 20 25 30 35 40 45 50
T69 ins
Q151M
Y115F
K65R
L74V/I
L210W
K70R
K219Q/E/N/R
D67N
M41L
T215Y/F
M184V/I
1%
1%
2%
4%
12%
15%
16%
20%
20%
25%
31%
44%
44thICAAC
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Phenotypic NRTI Resistance of HIV-1 Variants With K65R
Frequency and Characteristics of the NRTI-Associated K65R and L74V/I RT Mutations
% A
bo
ve C
ut-
off
ZDV(1.9)
d4T(1.7)
TDF(1.4)
ABC(4.5)
ddl(1.7)
3TC(3.5)
0
20
40
60
80
100
2 0 613
0
29
85
13
83
1
96
22
62
96
71
97100
99
NRTIs (PhenoSense cut-off)
K65R alone K65R + M184V K65R + NAMs
McColl DJ, et al. 44th ICAAC, 2004. Poster H-178.
44thICAAC
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Phenotypic NRTI Resistance of HIV-1 Variants With L74V/I
Frequency and Characteristics of the NRTI-Associated K65R and L74V/I RT Mutations
% A
bo
ve C
ut-
off
NRTIs (PhenoSense cut-off)
L74V/I + M184V L74V/I + NAMsL74V/I alone
100
ZDV(1.9)
d4T(1.7)
TDF(1.4)
ABC(4.5)
ddl(1.7)
3TC(3.5)
0
20
40
60
80
0 0
85
0 0
79
0 0
57
0
85
3629
92
55
3
100
63
McColl DJ, et al. 44th ICAAC, 2004. Poster H-178.
44thICAAC
www.medscape.com/hiv-aidshomeStaszewski S, et al. 44th ICAAC, 2004. Poster H-177.
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
Predictors of K65R With Tenofovir in Antiretroviral Therapy (ART)-Experienced and -Naive PatientsIn patients taking tenofovir, emergence of the K65R drug resistance mutation was associated with the
absence or presence of other specific regimen components.
44thICAAC
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Proportion of Patients With Reduced Susceptibility to > 1 Drug (N = 317)
Prevalence of Transmitted HIV Drug Resistance in ART-Naive Individuals in the United States in 2003
Ross LL, et al. 44th ICAAC, 2004. Poster H-173.
0 5 10 15 20 25
3 PI
2 PI
1 PI
> 1 PI
3 NNRTI
2 NNRTI
1 NNRTI
> 1 NNRTI
> 1 NRTI
Any ARV
% Subjects
23%
0.9%
18%
10%
3%
6%
6%
4%
0.9%
0.3%
NRTI mutations: 15% V118I (4%), D67N (1%), M41L (or mix, 1%)
NNRTI mutations: 6% K103N (3%), G190A (or mix, 1%), V108I (or mix, 1%)
Primary PI mutations: 4% None > 1%
Nucleoside/Nucleotide Reverse Transcriptase InhibitorOptions and Regimens
for First- and Second-line Therapy
44thICAAC
www.medscape.com/hiv-aidshomeMoyle G, et al. 44th ICAAC, 2004. Abstract H-1131.
Median HIV RNA (log10 copies/mL) 5.26 5.13
Median CD4+ (cells/mcL) 194 153
Trizivir + Tenofovir vs Combivir + Efavirenz in ART-Naive Patients
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)
ZDV/3TC 300/150 mg BID + Efavirenz 600 mg QD
Baseline characteristics were comparable, including:
or
A single-class, quadruple-NRTI regimen was shown to be equivalent to a standard, 2-class efavirenz-based regimen for first-line therapy.
44thICAAC
www.medscape.com/hiv-aidshomeMoyle G, et al. 44th ICAAC, 2004. Abstract H-1131.
Total cholesterol decreased significantly in Quad-NRTI arm: -0.2 mmol/L vs +0.8 mmol/L (P <.001)
1 virologic failure (Quad-NRTI)
ITT , intention-to-treat analysis; M=F, missing equals failure
0
20
40
60
80
100
0 4 8 12 24 36 48
EFV+ZDV/3TCQuad-NRTI
Treatment Time (Weeks)
% S
ub
ject
s 68 %67 %
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)
44thICAAC
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Proportion of Subjects With HIV-1 RNA <50 Copies/mLat Week 24
No of Subjects Overall <100,000 >100,000
ITT M=F 123 52 71
AT 94 40 54
ITT M=F AT
5465
46
7185
61
0
20
40
60
80
100
Overall BL VL<100,000
BL VL> 100,000
% S
ub
ject
s
Trizivir + Tenofovir in ART-Naive Subjects: COL40263
DeJesus E, et al. 44th ICAAC, 2004. Poster H-564.
27 subjects (22%) discontinued study
12 (9.8%) due to adverse events
9 (8%) had grade 3/4 lab abnormalities
8 (7%) had suspected ABC
hypersensitivity
Reductions in lipids were observed
8 virologic nonresponders• >1 TAMs only, 3
• >1 TAMs+M184V, 3
• Wild-type, 2
ITT, intention-to-treat analysis; M=F, missing equals failure; AT, as treated
44thICAAC
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Trizivir + Tenofovir in Patients With Early Virologic Failure on Initial Regimen: ESS30005
Rodriguez AE, et al. 44th ICAAC, 2004. Poster H-563.
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
Zidovudine/lamivudine/abacavir (Trizivir) + tenofovir may be a viable rescue option for patients with early virologic failure on a standard initial regimen.
44thICAAC
www.medscape.com/hiv-aidshomeRodriguez AE, et al. 44th ICAAC, 2004. Poster H-563.
Proportion of Subjects With HIV-1 RNA <50 Copies/mL Through Week 24
93%
80%
75%65%
Trizivir + Tenofovir in Patients With Early Virologic Failure on Initial Regimen: ESS30005
0
20
40
60
80
100
0 4 8 12 16 20 24
Treatment Time (Weeks)
% S
ub
ject
s
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
44thICAAC
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Tenofovir/Emtricitabine + Efavirenz vs Combivir + Efavirenz in ART-Naive Patients
Gazzard B, et al. 44th ICAAC, 2004. Abstract H-1137c.
Study 934: Open-label, randomized, noninferiority study
Better overall responses were seen with tenofovir/emtricitabine than with zidovudine/lamivudine (Combivir) in the preliminary analysis of this head-to-head study.
Tenofovir/Emtricitabine (n=255)
TDF 300 mg + FTC 200 mg
+ EFV (all QD)
Combivir (n=254)
ZDV/3TC 300/150 mg (BID)
+ EFV (QD)
or
Planned 24-week analysis (96-week study)
ART-naive patients were randomized to receive:
Baseline characteristics were comparable, including:
Median HIV RNA (log10 copies/mL) 5.0 5.0
% HIV RNA > 100,000 52 50
Median CD4+ (cells/mcL) 233 241
% < 200 42 41
44thICAAC
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Tenofovir/Emtricitabine + Efavirenz vs Combivir + Efavirenz in ART-Naive Patients
Time to Loss of Virologic Response (TLOVR) <50 Copies/mL (ITT)
ITT, intention-to-treat analysis
Gazzard B, et al. 44th ICAAC, 2004. Abstract H-1137c.
0
20
40
60
80
100
0 4 8 16 24
TDF/FTC ZDV/3TC
Treatment Time (Weeks)
% S
ub
ject
s 73%65%
P = .038
44thICAAC
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Tenofovir/Emtricitabine + Efavirenz vs Combivir + Efavirenz in ART-Naive Patients
Gazzard B, et al. 44th ICAAC, 2004. Abstract H-1137c.
TDF/FTC ZDV/3TC
Permanent Study Regimen Discontinuation (%)
11 21*
Adverse Event (%) 3 9†
Noncompliance/Lost Follow-up (%) 4 6
Suboptimal Virologic Response (%) 2 1
Other (%) 3 5
Patient Disposition Through Week 24
* P = .003 † P = .008
Significantly better overall response with tenofovir/emtricitabine due
to fewer adverse events leading to fewer discontinuations in that arm
5% (vs 0% ) discontinued due to anemia in the Combivir arm
44thICAAC
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Efficacy of Fixed-Dose Abacavir/Lamivudine + Efavirenz: ESS30009
Proportion of Subjects With HIV-1 RNA <50 Through Week 24 (ITT, M=F)
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%)
Treatment Time (Weeks)
% S
ub
ject
s
0
20
40
60
80
100
0 4 8 12 16 20 24
69%
Terminated
ABC/3TC+EFV
ABC/3TC+TDF
ITT, intention-to-treat analysis; M=F, missing equals failure
Gallant JE, et al. 44th ICAAC, 2004. Poster H-567.
44thICAAC
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Virologic Response Following Switch to Second-line Regimens up to 12 Weeks
Gallant JE, et al. 44th ICAAC, 2004. Poster H-567.
Predictors of a 12-week post-switch viral load < 50 copies/mL:
• Baseline viral load: OR, 0.163; P = .001
• Abacavir use: OR, 7.731; P = .009
Efficacy of Subsequent Treatment of Tenofovir + Abacavir/Lamivudine Nonresponders: ESS30009
Treatment Time Post Switch (Weeks)
% S
ub
ject
s
0
20
40
60
80
100
2 4 8 12
ITT M=F <400 ITT M=F <50
Obs <400 Obs <50
• Efavirenz use: OR, 5.797; P = .015
• Zidovudine use: OR, 5.032; P = .022
ITT, intention-to-treat analysis; M=F, missing equals failure; Obs, observed
44thICAAC
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Early Virologic Failure With Once-Daily Didanosine/Tenofovir/Efavirenz in ART-Naive Patients
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
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.
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%)*
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
*P < .05
Moyle G, et al. 44th ICAAC, 2004. Poster H-566.
44thICAAC
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Tenofovir/Didanosine: Paradoxical CD4+ Cell Declines Despite Good Virologic Control
Barrios A, et al. 44th ICAAC, 2004. Abstract H-1132.
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
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
Simplification/Switch Strategies for Patients With Virologic Suppression
44thICAAC
www.medscape.com/hiv-aidshomeCohen C, et al. 44th ICAAC, 2004. Poster H-577.
• Efavirenz + didanosine/lamivudine (all QD)
• Efavirenz + current NRTIs (ZDV/3TC, 51%; d4T/3TC, 30%; other, 19%)
Virologic Response at Week 24 (ITT NC=F):
Switching From a PI- to a Once-Daily Efavirenz-Based Regimen: VEST-QDOnce-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:
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
44thICAAC
www.medscape.com/hiv-aidshomeBonjoch A, et al. 44th ICAAC, 2004. Poster H-562.
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.
ZDV/3TC/ABC (n=68) ZDV/3TC/NVP (n=66)
% Undetectable VL (ITT NC=F) 71 73
% Undetectable VL (OT) 98.6 98.5
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
ITT, intention-to-treat analysis; NC=F, noncompletion equals failure
44thICAAC
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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.
44thICAAC
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Favorable Lipid Changes With Switch From Stavudine to Tenofovir: GS903E
Suleiman JMAH, et al. 44th ICAAC, 2004. Poster H-158.
Mean Changes in Fasting Lipid Parameters After d4T to TDF Switch
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
*P < .001
Week 12(n=85)
Week 24(n=83)
Mea
n C
han
ge
(mg
/dL
)
-70
-60
-50
-40
-30
-20
-10
0
-23*-17*
-6* -4*-0.2 -0.2
-40*-38*
-62*
-44*
TC LDL-C HDL-C LDL-C/HDL-C TG
Current and Investigational Protease Inhibitors
44thICAAC
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Favorable Increases in HDL-Cholesterol With Fosamprenavir in ART-Naive Patients: NEAT
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:
In the NEAT study, treatment with unboosted fosamprenavir + abacavir/lamivudine was associated with increases in high-density lipoprotein cholesterol (HDL-C) levels.
Mean Change From Baseline at Week 48 Fosamprenavir Nelfinavir
Total cholesterol (TC) (%) -1 +12
HDL-C (%) +37 +22
TC/HDL-C ratio (%) +31 +29
Triglycerides (mg/dL) +2 +46
Nadler JP, et al. 44th ICAAC, 2004. Poster H-156.
44thICAAC
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Increases in HDL-C to Maximum Post Baseline by NCEP Lipid Category
Favorable Increases in HDL-Cholesterol With Fosamprenavir in ART-Naive Patients in the NEAT Study
<40 mg/dL
>40 to <60 mg/dL
>60 mg/dL69
24
76
47
27
49
21
43
2710
0%
20%
40%
60%
80%
100%
BL Max. post-BL
BL Max. post-BL
Fosamprenavir (n=148) Nelfinavir (n=72)
% S
ub
ject
s
Nadler JP, et al. 44th ICAAC, 2004. Poster H-156.
44thICAAC
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Tipranavir/Ritonavir vs Other Boosted PIs in ART- Experienced Patients: RESIST-1
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:
Following 24 weeks of treatment, tipranavir/ritonavir appeared to be superior to other boosted PIs in patients with PI-resistant virus.
Tipranavir (n=311)
Tipranavir/ritonavir 500/200 mg + optimized background regimen
Comparator PI (n=309)
Comparator PI/ritonavir + optimized background regimen
36.1% of subjects received enfuvirtide
or
Hicks C, et al. 44th ICAAC, 2004. Abstract H-1137a.
44thICAAC
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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
481325
139
109
9
ALT elevation (%) 6.9 1.3 *
Cholesterol (%) 4.2 0*
Triglycerides (%) 21.7 12.5†
Rates of grade 3/4 side effects were similar overall (22.8% and 18.1%) but differed significantly for certain parameters:
* P < .001 † P < .01
Tipranavir/Ritonavir vs Other Boosted PIs in ART- Experienced Patients: RESIST-1
Discontinuations and Adverse Events
Hicks C, et al. 44th ICAAC, 2004. Abstract H-1137a.
44thICAAC
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Virologic Responses at 24 Weeks (ITT, LOCF)
< 400 copies/mL < 50 copies/mL
*P < .001
34.7
16.5
25.1
10
0
20
40
60
Tipranavir Comparator PI
*
*
**
% S
ub
ject
s
*P < .001
Tipranavir/Ritonavir vs Other Boosted PIs in ART- Experienced Patients: RESIST-1
Hicks C, et al. 44th ICAAC, 2004. Abstract H-1137a.
ITT, intention-to-treat analysis; LOCF, last observation carried forward
44thICAAC
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Impact of Enfuvirtide (ENF) on Virologic Responses (ITT, LOCF)
% S
ub
ject
s
< 400 copies/mL < 50 copies/mL
Tipranavir/r Comparator PI
0
All +ENF All +ENF All +ENF All +ENF
20
40
60
34.7
47.1*
16.5
21.9* 25.1
32.8*
10.014.3*
*P < .001
Tipranavir/Ritonavir vs Other Boosted PIs in ART- Experienced Patients: RESIST-1
Hicks C, et al. 44th ICAAC, 2004. Abstract H-1137a.
ITT, intention-to-treat analysis; LOCF, last observation carried forward
CCR5 Antagonists and Viral Tropism
44thICAAC
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873140, a Novel CCR5 Antagonist: 10-Day Responses to Monotherapy
Lalezari J, et al. 44th ICAAC, 2004. Abstract H-1137b.
Median Change in Viral Load at Day 10 by Dose Group
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
HIV
-1 R
NA
(lo
g10
co
pie
s/m
L)
-0.12
-0.46
-1.23
-1.03
-1.66-1.8
-1.6
-1.4
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
Placebo(n=9)
200 QD(n=7)
200 BID(n=8)
400 QD(n=8)
600 BID(n=8)
44thICAAC
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Distribution of Coreceptor Tropism According to Treatment Status
Demarest J, et al. 44th ICAAC, 2004. Abstract H-1136.
Tropism
% S
amp
les
Total
ART-Naive
ART-Experienced
n = 339 263 76 67 6 63136
82
16
2
88
12
0
67
28
5
0
20
40
60
80
100
R5 R5/X4 X4
Relative Distribution of HIV-1 Tropism Among ART-Naive and -Experienced Patients*
* Source = 442 stored samples from GlaxoSmithKline clinical trials; 412 were successfully typed
44thICAAC
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Distribution of Coreceptor Tropism According to CD4+ Cell Count
Moyle G, et al. 44th ICAAC, 2004. Abstract H-1135.
% X
4 o
r R
5/X
4
16 16
41.9 40
14.8
0
20
40
60
80
> 300 (n=248)
> 201-300(n=104)
> 101-200(n=81)
> 51-100(n=31)
< 50(n=50)
CD4+ cell count (cells/mcL)
Prevalence of R4- or R5/X4-Tropic Isolates by Absolute CD4+ Cell Count*
* Source = 865 stored samples from Chelsea and Westminster Hospital, London; 616 were successfully typed