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Selected Controversies in Antiretroviral Therapy. Joel E. Gallant, MD, MPH Johns Hopkins University School of Medicine. When to Start Therapy?. Will We Return to Earlier Therapy?. Availability of more potent, easier, and less toxic regimens. 1996: ddI + d4T + SQV - PowerPoint PPT Presentation
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Selected Controversies in Selected Controversies in Antiretroviral TherapyAntiretroviral Therapy
Joel E. Gallant, MD, MPH
Johns Hopkins University School of Medicine
When to Start Therapy?When to Start Therapy?
Will We Return to Earlier Therapy?
Availability of more potent, easier, and less toxic regimens
The Move Toward Simpler Regimens3-drug regimens: 1996 and 2005
1996: ddI + d4T + SQV
-SQV: 6 q8h with fatty food
-ddI: 2 bid ½ hr ac or 2 hrs pc
-d4T: 1 pill bid
-24 pills/d, 5 doses
-significant long-term toxicity
2005:TDF/FTC or ABC/3TC + EFV
-2 pills qd
-no food restrictions
-no long-term toxicity anticipated
One Pill, Once Daily Triple Combination Regimen?
tenofovir + emtricitabine + efavirenz
0 10 20 30 40 50 60 70 80 90 100% With VL < 50 at Week 48
Boosted PI
NNRTI
NRTI
Unboosted PI
Collated Results of HAART Studies
Bartlett JA et al. Abstract 586.
Previous analysis emphasized relation b/w pill burden and response
Updated analysis: pill burden less important
Highlights efficacy of boosted-PI and NNRTI regimens
0
15
30
45
60
75
90
105
120
135
150
Med
ian
CD
4+ In
crea
se
97
119 120 121127 125
150Median CD4+ increase
Treatment Responses in 1st Year of HAARTImproving Over Time
4143 subjects from 5 clinic cohorts in Europe and Canada Treatment-naive; started HAART from 1996-2002 ↓ risk of virologic failure, ↑ med. CD4 increase in later years
» In recent years, most “failure” due to loss to follow-up or treatment discontinuation
Lampe S, et al. 12th CROI, 2005, Abstract 593
24.8 23.017.3
12.4 10 8 8.4
0
10
20
30
40
50
1996 1997 1998 1999 2000 2001 2002
% with > 500 copies/mL
60
70
80
90
100
% W
ith
VL
> 5
00 o
n A
RT
What Degree of Adherence is Needed? Data From Unboosted PIs
Adherence to a PI-containing regimen correlates with HIV RNA response at 3 months
% V
L <
400
co
pie
s/m
L
PI Adherence, % (MEMS caps)
0
20
40
60
80
100
< 70 70–80 80-90 90–95 > 95
Paterson DL, et al. Ann Intern Med. 2000;133:21-30.
Adherence and Virologic Suppression:NNRTIs vs. unboosted PIs
Bangsberg DR et al. 12th CROI, 2005. Abstract 616.
PINNRTI
0-53 54-73 74-93 94-1000
20
40
60
80
100
% V
L <
400
co
pie
s/m
L
% Adherence (Pill Count)
0-53 54-73 74-93 94-1000
20
40
60
80
100
% Adherence (Electronic Measurement)
109 indigent patients in San Francisco: 56 on unboosted PIs, 53 on NNRTIs VL < 400 reliably seen with NNRTI if adherence > 54%, but with unboosted
PI, only with very high adherence Predictors of VL < 400: NNRTI use, adherence, high CD4 nadir, time on Rx
Will We Return to Earlier Therapy?
Availability of better, easier, and less toxic regimens Conflicting cohort data: some studies show benefit
with earlier therapy
Cohort Studies Supporting Earlier Therapy
Swiss Cohort: Better prognosis with initiation of HAART at CD4 >3501
HOPS: Trend toward lower mortality in pts treated with CD4 351-5002
ALIVE: Survival of HIV+ IDUs only approximated that of HIV- IDUs when HAART initiated at CD4 >3503
1. Opravil M, et al. AIDS 2002; 2. Palella FJ, et al. Ann Intern Med 2003; 3. Wang C, et al. J Infect Dis 2004
Will We Return to Earlier Therapy?
Availability of more potent, easier, and less toxic regimens
Conflicting cohort data: some studies show benefit with earlier therapy
Risk of prolonged HIV exposure independent of CD4? (dementia, NHL, PML, KS)
Will We Return to Earlier Therapy?
Availability of more potent, easier, and less toxic regimens
Conflicting cohort data: some studies show benefit with earlier therapy
Risk of prolonged HIV exposure independent of CD4? (dementia, NHL, PML)
Maintain options for intermittent therapy
Intermittent CD4-Guided TherapyThe BASTA Study
Maggiolo F, et al. 43rd ICAAC, Chicago, September 2003, H-448
• 18/76 (24%) restarted HAART at least once
• 95% in STI group have maintained CD4 >400 at 20 months of follow-up
• Better lipid profiles in STI group:
• Only nadir CD4 <350 cells/mm3 predicted time to restart HAART
• Cost of care in STI group decreased by ~€300/month
114 patients:CD4 >800 cells/mm3
HIV RNA <50 c/mL
Continuous therapy(n=38)
Restart therapy when CD4 <400 cells/mm3
(n=76)
Characteristics:3.2 prior ARV regimens
57 mo of prior ARVPre-ARV RNA: ~100,000 c/mL
The BASTA Study: Maggiolo’s Conclusion
“…“…therefore, we should start therapy therefore, we should start therapy earlier so we can stop.” earlier so we can stop.”
CD4-Guided Intermittent TherapyC
D4
Cou
nt
CD4 Treatment threshold
= on HAART Time
Treatment interruption (years)
CD4 nadir = strongest predictor of time off therapy
Will We Return to Earlier Therapy?
Availability of more potent, easier, and less toxic regimens
Conflicting cohort data: some studies show benefit with earlier therapy
Risk of prolonged HIV exposure independent of CD4? (dementia, NHL, PML)
Maintain options for intermittent therapy Preserve R5-tropic status
How Will We Use New Agents?How Will We Use New Agents?
Targets for Antiretroviral Therapy
Reverse Reverse Transcriptase Transcriptase
InhibitorsInhibitors
Protease Protease InhibitorsInhibitors
Integrase Integrase InhibitorsInhibitors
EntryEntryInhibitorsInhibitors
PIsPIs
NRTIs,NRTIs,NNRTIsNNRTIs
Attachment Attachment Inhibitors, Inhibitors, Coreceptor Coreceptor AntagonistsAntagonists
Maturation Maturation InhibitorsInhibitors
Fusion Fusion InhibitorInhibitor
NRTIs/NtRTIs» SPD 754 (DOTC)
» Amdoxovir (DAPD)
» D-D4FC
» Alovudine (MIV 310)
» Racivir (+/–FTC)
» SN1212
» Compound X
Protease inhibitors» TMC114
» GW0385
» P-1946
Entry inhibitors» Aplaviroc
» Maraviroc
» Vicriviroc
» BMS-488043
» TNX-355
» NB-2, NB-64
» T-649
NNRTIs» TMC125» GW678248
(prodrug = GW695634)» TMC278» BILR 355 BS» CSIC» DAPY/DATA» UC781» TMC120 (as microbicide)
New Antiretrovirals in Development
CCR5 Inhibitors in Development
OaLb0203 -2.0
-1.5-1.0
-0.5
0
0.5
Placebo 15Placebo 0725 mg QD50 mg BID100 mg QD
100 mg BID150 mg Fast150 mg Fed300 mg QD300 mg BID
0 5 10 15 20 25 30 35 40
Time (days)
10 mg BIDPlacebo
25 mg BID50 mg BID
HIV-infected volunteers (N = 48)
0.5
0.0
-0.5
-1.0
-1.5
0 5 10 15 20 25 30
Days
Dosing Period Washout Period
Vicriviroc (SCH-417690)
Maraviroc (UK-427857)
Dosing
Greater risk of postural hypotension
Me
dia
n V
L C
ha
ng
e F
rom
B
L (
log
10 c
op
ies
/mL
)
-1.8-1.6-1.4-1.2
-1-0.8-0.6-0.4-0.2
5 10 15 20 25 30
00.2
0
Placebo200 QD
0.4
Day
200 BID 400 QD 600 BID
Dosing
Most common AE: minor, self-limiting GI
events
Aplaviroc (GW873140)
Me
dia
n V
L C
ha
ng
e F
rom
B
L (
log
10 c
op
ies
/mL
)
Me
dia
n V
L C
ha
ng
e F
rom
B
L (
log
10 c
op
ies
/mL
)
Increasing Prevalence of X4- or R5/X4-Tropic Virus At Lower CD4 Counts
CCR5: Pts with early stage HIV-disease tend to
have pure R5-tropic virus
CXCR4: With advanced disease, X4- or dual-
tropic virus emerges Associated with more rapid clinical and
immunologic progression
CCR5 inhibition: could select for more virulent X4-tropic virus
Moyle G, et al. Abstract 1135, 44th ICAAC, Washington, 2004
16 16 14.8
41.9 40
0
10
20
30
40
50
60
70
80
> 300
248
Pre
val
en
ce
of
X4
or
R5
/X4
, % 90
100
> 201-300
104
> 101-200
81
> 51-100
31
< 50
50
CD4 count
n =
Emergence of R5/X4 Virus During Maraviroc Monotherapy: Selection of Baseline Variants
Lewis ME, et al. ICAAC 2004. Abstract 584b.
0
20
40
60
80
100
Prescreen
% o
f E
nve
lop
e C
lon
es
Day 1 Day 11
n = 67R5X4R5/X4
Day 40 Day 203 Day 251 Day 308 Day 373
n = 118
n = 52 n = 63
n = 46 n = 44 n = 49 n = 48
0
20
40
60
80
100
% o
f E
nve
lop
e C
lon
es
R5R5/X4
Day 1 Day 11 Day 40
n = 97
n = 68n = 91
Tropism assay threshold ~ 10%
Treatment selects for preexisting minority variants
Patient A
Patient B
CCR5 Inhibitors for Initial Therapy
PROs: Naïve patients less likely to have X4- or R5/X4-tropic virus Well tolerated and convenient in early trials
CONs: Tough competition (e.g. 1 pill qd, well tolerated, with minimal
long-term toxicity) May require tropism screening: more expensive if used up-front
before initial therapy in all patients
Which agent(s) would it replace?
CCR5 Inhibitors for Experienced Patients
PROs: Effective against NRTI-, NNRTI-, and PI-resistant virus May be synergistic with other entry inhibitors (e.g. ENF) Cost of tropism assay easier to justify in subset of patients failing therapy
CONs: Greater likelihood of X4- or R5/X4-tropic virus with more treatment
experience or more advanced disease Efficacy with dual-tropic virus depends on activity of other drugs in
regimen, which decreases with greater treatment experience.
Integrase Inhibitors: Short-term Monotherapy with L-870,810
Randomized, double-blind, placebo-controlled, 10-day dose-finding study 200 mg BID (n=7) vs 400 mg BID (n=17) vs placebo (n=6)
Development stopped due to preclinical toxicity, but proof of concept demonstrated Other candidate being evaluated Little S, et al. 12th CROI, # 161
Days since randomization
On therapy Post therapy
Δ f
rom
bas
elin
e H
IV
RN
A
log 1
0 c/
mL
–2
–1
0
1
2
1 3 8 10 17 24
–2
–1
0
1
2
L-000870810 200 mg L-000870810 400 mg Placebo
How Will We Use Integrase Inhibitors?
Too soon to tell…» Depends on potency, convenience,
tolerability, toxicity» Unlike CCR5 inhibitors, there appear to be
no other specific considerations that argue for earlier or later use
Can “2nd Generation” Agents Move to the Head of the Line?
Yes: LPV/r started out as a “salvage drug” but became a 1st-
line PI because of greater potency, durability, and lack of resistance with failure
Other examples: TDF, ABC
What does it take to become 1st-line in a class? Advantages with respect to tolerability, toxicity,
convenience, durability, and/or resistance profile
The Potential for Earlier Use of 2nd Generation Agents
PIs » Tipranavir: unlikely because of higher RTV dose, greater PI toxicity, pill
burden, bid dosing» TMC 114: more likely than TPV, though still bid with higher pill burden than
current standards
NNRTIs» TMC 125: unlikely because of higher pill burden vs. EFV» TMC 278: low pill burden, potential for earlier use if better tolerated than
EFV
NRTIs» D-d4FC: qd dosing, but need data on resistance profile with failure
Tipranavir/Ritonavir Superior to Lopinavir/Ritonavir in RESIST Studies
TPV/r superior to LPV/r at Week 24 in PI-experienced patients In subgroups in each arm receiving same total number of active drugs,
TPV/r arm remained superior
Cooper D, et al. ICAAC 2005, Abstract 560.
45.335.2 39.636.1
10.721.4
0
20
40
60
80
100
LPV/rNaive
LPV/r Experienced
Overall
45.735.8 39.639.6
13.121.4
0
20
40
60
80
100
LPV/r Susceptible
LPV/rResistant
Overall
TPV/rLPV/r
% W
ith
VL
≥1
log
10 c
/mL
P < .05 P < .0001 P < .05 P < .0001
TPV Mutation Score vs IAS-USA Protease Gene Resistance Mutations
Many mutations (13, 35, 43, 58, 74, 83) have not been associated with resistance to other PIs Major mutations (D30N, G48V, N88D, L90M) associated with other PIs do not contribute to
TPV mutation score
10
S
C
SAMV
TTAVVIR
SFSTLVALLFMI
MDVAICVpVLLVVIIIINIRF
9088848277 7371 63 545350484746 36 3332302420 IAS-USA
LNIVVCALIFIGIMMLVDLKL
VV
TMR
VLPKEAVLTIGFMV
848382 74 69 5854 474643363533 2013 10TPV
IVTHQIIMKMELKI
Score
D
N
V
L
Relationship of TPV Score to TPV Phenotype Results and Response
Valdez H, et al. Resistance Workshop 2005. Abstract 27.
-2
-1
0
-3
Med
ian
Ch
ang
e in
VL
at
Wk
24*
(lo
g10
co
pie
s/m
L)
0-1 2-3 4-5 6-7 8-9
-2.10(n = 144)
-0.89(n = 242)
-0.45(n = 260)
-0.49(n = 68)
-0.08(n = 4)
TPV Score
Median FC: 0.7-0.9 1.1-1.4 2.0-3.1 3.3-3.9 14.7-52.5
*24-week data from patients in RESIST-1 and -2 given TPV/r
POWER1: Virologic Response to TMC114/r
LB0102
Time (weeks)
Pat
ien
ts w
ith
HIV
-1 R
NA
< 5
0 co
pie
s/m
L (
%)
0
1 2 4 8 12 16 20 24
TMC114/r 400 QD (n = 64)TMC114/r 800 QD (n = 63)TMC114/r 400 BID (n = 63)TMC114/r 600 BID (n =65)Comparator PIs (n = 63)
P < .001 for all doses80
60
20
40 43%48%49%53%
18%
100
New Trends in Resistance and New Trends in Resistance and Drug SequencingDrug Sequencing
Sequencing therapy in 2006 and beyond: how many tries do you get?
• One of many plausible scenarios:2 NRTIs + 1 NNRTI
→ 3 NRTIs + 1 PI/r → 1 PI/r + CCR5 inhibitor +/- NRTIs → integrase inhibitor + ENF + other CCR5 inhibitor +/-PI/r → maturation inhibitor + other entry inhibitor(s) + ?
• Problems:• People who fail initial therapy today were probably non-adherent with
simple regimens• The “first shot’ may always be the “best shot”• Infection with resistant virus can eliminate many sequences
Resistance Mutations:What’s “In” and What’s “Out” in 2005
OUT TAMs
» Selected by ZDV and d4T, which will be used less frequently in initial therapy
» Usually absent with initial failure» Impact of generic ZDV?
PI mutations» Typically absent with early failure of boosted PIs
Resistance Mutations:What’s “In” and What’s “Out” in 2005
IN M184V
» 3TC and FTC are used in all initial regimens» M184V emerges quickly with failure
NNRTI mutations» NNRTIs used widely for initial therapy» NNRTI resistance emerges quickly with failure
K65R, L74V» Still not widely seen, but more likely to be selected by today’s regimens» May not be preventable with early modification
ENF mutations» Emerge rapidly with non-suppressive ENF-containing therapy
GS934: Efficacy and Tolerability48-week data
Pozniak AL, et al. IAS 2005. Abstract WeOa0202.
Excluding pts with baseline NNRTI resistance
FTC + TDF 80% vs AZT/3TC 70% (P = .021)
AEs leading to D/C
FTC + TDF + EFV
(n = 257)
AZT/3TC + EFV
(n = 254)
Any AE 10 (4%) 23 (9%)*Anemia 0 14 (6%)
Nausea 1 (1%) 4 (2%)
Fatigue 0 3 (1%)
Vomiting 0 2 (1%)
Dermatitis 2 (1%) 0
Neutropenia 0 2 (1%)
Differences in efficacy primarily due to differences in discontinuation due to AEs
* P = .016
Pat
ien
ts w
ith
HIV
-1 R
NA
<
400
co
pie
s/m
L [
TL
OV
R]
(%)
77%
68%
P = .034
FTC + TDF + EFV AZT/3TC + EFV(ITT n = 509)
0
20
40
60
80
BL 8 16 24 32 40 48
100
Weeks
GS934: Resistance Analysis
BL NNRTI resistance mutations ↓ response, whereas BL NRTI resistance mutations had little impact» 2/22 (9%) with BL NNRTI-R had VL < 400 at Wk 48» 12/13 (92%) with BL NRTI-R had VL < 400 at Wk 48
Resistance Mutations at Wk 48
FTC + TDF + EFV(n = 244)
ZDV/3TC + EFV(n = 243)
Resistance analysis, n (%) 12 (5%) 23 (10%)
Population n (% mITT, % RAP) n (% mITT, % RAP)
Any resistance mutations 9 (4%, 75%) 17 (7%, 77%)
Any EFV-R 9 (4%, 75%) 16 (7%, 73%)
Any M184V/I 2 (1%, 17%) 7 (3%, 32%)
Any TAM 0 1 (< 1%, 5%)
K65R 0 0
McColl D, et al. IAS 2005. Abstract TuPp0305. % mITT, % of patients in modified intent-to-treat analysis; % RAP, % in patients with resistance testing
“Nuke-Sparing Regimens”: The Latest Thing or Old News?
Rationale was based on concerns about inevitable mitochondrial toxicity with NRTIs
Role of NRTIs on Change in Limb Fat (ACTG 5005)
*P<0.05 between groups; †P<0.05 within groups. Dube M, et al. 2002; 4th Lipo Wkshp. Abstract 27.
IQR
** *
†
††
†
††
N=156; analysis by intent to treat
Me
dia
n %
ch
ang
e f
rom
ba
sel
ine
-30
-20
-10
0
10
20
Study Week
AZT/3TC ddI+d4T
Entry 16 32 48 64 80
“Nuke-Sparing Regimens”: The Latest Thing or Old News?
Rationale was based on concerns about inevitable mitochondrial toxicity with NRTIs» These concerns have subsided with greater use of
“mitochondria-friendly” NRTIs (TDF, ABC, 3TC, FTC)
RAVE Study: Switch Thymidine Analog to ABC or TDF
Suppressed patients with self-defined lipoatrophy on thymidine analog (TA)
105 pts randomized to replace TA with TDF or ABC
Total limb fat increased to similar extent in both arms over 48 weeks
Moyle G, et al. 12th CROI, 2005, Abstract 44LB.
Ch
ang
e i
n f
at
mas
s (g
) b
y D
EX
A,
Wk
48
393522
1061
316
791
1046
0
200
400
600
800
1000
1200
Limb Trunk Total Fat
TDFABC
Within-group change in limb fat from baseline: TDF P = .01, ABC P = .001
GS 903E: Impact of Switching off d4T on Lipids and Limb Fat
96-week open-label extension phase of 903 study» Data from subgroup of pts given d4T for 144 weeks who
switched to open-label TDF for 48 weeks
Madruga JVR, et al. IAS 2005. Abstract TuPe2.2b12.
Mea
n C
ha
ng
e in
Fas
tin
g
Lip
ids
at W
eek
48 (
mg
/dL
)
TGs TC LDL HDL
-80
-60
-40
-20
0
-72
-38
-16
-1
Mea
n T
ota
l L
imb
Fa
t (k
g)
p = 0.005
0
4.2
4.4
Wk 96 Wk 144 Wk 48post-switch
P < .0014.6
4.8
5.05.02
(n = 74)
4.60(n = 74)
d4T TDF
“Nuke-Sparing Regimens”: The Latest Thing or Old News?
Rationale was based on concerns about inevitable mitochondrial toxicity with NRTIs» These concerns have subsided with greater use of “mitochondria-
friendly” NRTIs (TDF, ABC, 3TC, FTC)
Recent data show greater toxicity with PI/NNRTI regimens (e.g. LPV/r + EFV)
Could new classes (e.g. CCR5 inhibitors) replace NRTIs?» Depends in part on long-term safety of TDF and ABC
Study 934
Serum Creatinine: week 48
Maximum Confirmed Toxicity Grade (mg/dL)a
FTC/TDF(n = 257)
CBV(n = 254)
Grade 1 (>1.5 - 2.0) 0 1 (<1%)
Grade 2 (2.1 - 3.0) 0 1 (<1%)
Grade 3 (3.1 - 6.0) 0 0
Grade 4 (>6.0) 0 0
a. Confirmed toxicity grade = 2 consecutive visits
‡
Arribas, J, et al. 18th International Conference on Antiviral Research, April 10, 2005. Barcelona, Spain
# on TDF 335 304 247 185
# on NRTI 403 369 297 172
*
*
0
20
40
60
80
100
120
0 90 180 270 360 450 540Days
GF
R (
ml/
min
/1.7
32 )
TDFNRTI
The Hopkins Cohort: TDF and Renal Function
Gallant JE, et al. 3rd IAS, Rio de Janeiro, 2005
Decline in ClCr independently associated with TDF use, baseline CD4<50, and duration of therapy
No association with age, race, sex, HIV transmission group, HTN, diabetes, HIV RNA, use of LPV/r or other specific ARV agents, or prior use of adefovir
Although statistically significant, clinical significance unclear: no difference in discontinuation
Majority of TDF-treated subjects remain on TDF and will continue to be followed
Johns Hopkins Cohort Conclusions
Gallant JE, et al. 3rd IAS, Rio de Janeiro, 2005
When to Use the New Agent
Too soon:» New drug used in combination with partially
active drugs despite relatively preserved CD4
Case 1
45-year-old man with multi-class resistance» Phenotype shows partial susceptibility to:
– TPV (FC 3.8)– TDF (FC 1.3)– ddI (FC 1.4)
CD4 326, VL 52,000 He is switched to TPV/r + TDF + ddI + ENF
When to Use the New Agent
Too soon:» New drug used in combination with partially
active drugs despite relatively preserved CD4 Too late:
» Use of new drug deferred until patient resistant to all other available drugs
Case 2
36-year-old man with treatment failure 1998: Began AZT/3TC + EFV 2000: Switched to ABC + 3TC + SQV/RTV
because of failure with NNRTI resistance Current status:
»CD4 180 (down from 240 three months ago)»VL 40,230 (increased from 13,452 3 months ago)»Phenotype: Susceptible to TDF, ddI, d4T, APV, LPV
Case 2
36-year-old man with treatment failure 1998: Began AZT/3TC + EFV 2000: Switched to ABC + 3TC + SQV/RTV
because of failure with NNRTI resistance Current status:
»CD4 180 (down from 240 three months ago)»VL 40,230 (increased from 13,452 3 months ago)»Phenotype: Susceptible to TDF, ddI, d4T, APV, LPV
Started on LPV/r + FPV + TDF + ddI
TORO: % w/ VL <400 c/mL through Week 48
(ITT, D/C + Switch = Failure)Patients on LPV/r with LPV susceptibility and > 2 other susceptible agents in OB
Draft
0102030405060708090
100
0 4 8 12 16 20 24 28 32 36 40 44 48
Study Week
% o
f P
atie
nts
ENF-based regimens (n=98)Regimens without ENF (n=59)
TORO: Change in VL from BL(D/C=Censored)
-3
-2
-1
0
0 4 8 12 16 20 24
Weeks Since Switch or BL
Med
ian
Pla
sm
a H
IV-1
RN
A
Lo
g C
han
ge f
rom
Baseli
ne
ENF+OB Switch
When to Use the New Agent
Too soon:» New drug used in combination with partially
active drugs despite relatively preserved CD4 Too late:
» Use of new drug deferred until patient resistant to all other available drugs
Just right:» New drug combined with other active new
agents, or use deferred until other new agents available
% with VL < 50 at Week 24 (ITT NC=F)
67% (n = 27)16% (n = 25)
37% (n = 27)8% (n = 39)
48% (n = 40)5% (n = 56)
45% (n = 38)5% (n = 42)
31% (n = 16)0% (n = 13)
ENF Used (Naive)
ENF Not Used
3 Primary PI Mut
TMC114 FC > 4
No Sensitive ARV in OBR
0 20 40 60 80
TMC114/r 600/100 BIDControl
47% (n = 64)9% (n = 74)
Overall
100
Katlama C, et al. CROI 2005, Abstract 164.
Subgroup Analyses of Response to TMC114/r 600/100 mg BID
“Salvage Therapy Only Works When it’s Not Really Salvage Therapy”
-Joep Lange
www.hopkins-hivguide.org