New HIV Therapy

1
New HIV Therapy

• Anton Pozniak
• Chelsea and Westminster Hospital
• London UK

2
What Nucleosides?
3
(No Transcript)
4
(No Transcript)
5
Gilead 903 96 Week Virologic Response
Intent to Treat (Missing Failure)
lt400 c/ml
100
82 vs. 78
80
78 vs. 74
lt50 c/ml
60
Patients undetectable
40
TDF3TCEFV
20
d4T3TCEFV
0
8
16
24
32
40
48
56
64
72
80
88
96
4
Weeks
Staszewski S et al. 10th CROI, Boston MA,
February 2003. Abs 564b
6
Gilead 903 Fasting Lipid Profile at Week 96
140
120
d4T 3TC EFV

100
TDF 3TC EFV
80
Mean Change (mg/dL)
Plt0.001
60

P0.032
40

20

0
Triglycerides
Cholesterol
LDL
HDL
Staszewski S et al. 10th CROI, Boston MA,
February 2003. Abs 564b
7
Gilead 903 96 Week Tolerability
TDF3TCEFV (n299)
d4T3TCEFV (n301)
Grade 3-4 AEs
Patients () with Events
70 (23)
67 (22)
Rash
7 (2)
7 (2)
Bacterial Infection
7 (2)
3 (1)
Depression
6 (2)
4 (1)
Fever
5 (2)
1 (lt1)
Pneumonia
4 (1)
6 (2)
Selected AEs
Peripheral Neuropathy
8 (3)
29 (10)
Lipodystrophy
3 (1)
35 (12)
Lactic Acidosis
0
3 (1)
Investigator defined
Staszewski S et al. 10th CROI, Boston MA,
February 2003. Abs 564b
8
Which NNRTI ?
9
2NN Design
1216 HIV treatment-naïve patients
NVP ODEFV OD (N209)
Due to NRTIs used all arms are BID
NVP BID (N 387)
NVP OD (N220)
D4T3TC
The study was powered to show non-inferiority
(10 difference)
Main objective Head-to-head lt50 copies 48 weeks
EFV OD (N400)
van Leth et al. 10th CROI, Boston MA, February
2003. Abs 176
10
Treatment success and failure
100
failure component
29.1
22.0
20.0
34.5
(whichever comes first)
75
change Rx
15.3
18.9
11.4
disease progression
of patients
16.3
50
virologic
success
25
56.4
56.3
62.3
46.9
0
NVP-od
NVP-bd
EFV
NVPEFV
Success only significant difference EFV vs
NVPEFV, plt 0.001
8
Frank van Leth
Viramune is not licensed for once-daily dosing
in the UK
11
Virologic success
100
75
patients
with virologic success
50
25
65.0
63.6
61.7
67.8
0
NVP-od
NVP-bd
EFV
NVPEFV
No significant differences in any of the pairwise
comparisons
9
Frank van Leth
Viramune is not licensed for once-daily dosing
in the UK
12
Virologic successby baseline pVL
overall
baseline pVL lt 5log
10
baseline pVL gt 5log
100
10
75
patients
with virologic success
50
25
65.0
51.5
63.6
53.7
61.3
57.1
61.7
67.8
71.1
64.0
71.1
68.2
0
NVP-od
NVP-bd
EFV
NVPEFV
10
Frank van Leth
Viramune is not licensed for once-daily dosing
in the UK
13
pVL lt 50 copies/mLITT

percentage of patients
p0.193
weeks after start allocated treatment
EFV
n400
70.0
NVP EFV n209
62.7
11
Frank van Leth
Viramune is not licensed for once-daily dosing
in the UK
14
pVL lt 50 copies/mLOT

percentage of patients
p0.064
weeks after start allocated treatment
88.7
142
NVP-bd
n378 336 306 305
291
282
275
81.5
86.8
EFV
n381 342 329 322
310
299
289
NVPEFV n199 170 149 145
137
130
127
79.5
12
Frank van Leth
Viramune is not licensed for once-daily dosing
in the UK
15
Increase in CD4 cellsOT
)
3
13
Frank van Leth
Viramune is not licensed for once-daily dosing
in the UK
16
Grade 3 or 4 clinical adverse events(all
isolated laboratory events excluded)
NVP-od
NVP-bd
EFV
NVPEFV
p-value
n220
n387
n400
n209

Hepato-biliary
1.8
2.6
0.5
1.0
0.082
hepatotoxicity
1.4
2.1
0.3
1.0
Cutaneous
4.1
3.6
3.8
5.7
0.619
rash
4.1
3.1
1.8
3.8
CNS / Psychiatric
1.4
3.6
5.5
7.7
0.001
insomnia / abn. dreams
-
-
1.5
2.4
anxiety
-
-
1.0
1.4
depression
-
0.3
1.5
0.5
Miscellaneous
diarrhoea
0.5
0.8
1.0
1.9
vomiting
0.9
1.0
1.0
1.4
pyrexia
0.9
2.1
0.8
1.0
Total of patients
15.0
20.4
18.0
24.4
0.077

Total of patients discont.
24.1
21.2
15.5
29.7
lt0.001
patients with at least one grade 3/4 event.
patients temporarily or permanently discontinuing
Rx because of AE (any grade)
14
Frank van Leth
Viramune is not licensed for once-daily dosing
in the UK
17
Grade 3 or 4 laboratory toxicities
NVP-od
NVP-bd
EFV
NVPEFV
p-value
n220
n387
n400
n209

Hepatobiliary lab. toxicity
13.2
7.8
4.5
8.6
0.002
Non-hepatobiliary lab. toxicity
8.2
12.9
8.8
9.6
0.161
neutropenia
2.3
3.9
1.8
5.3
amylase
1.8
3.1
3.5
1.4
triglycerides
1.4
1.3
1.3
0.5
alkaline phosphatase
0.5
1.3
0.8
1.9
elevated ASAT and/or ALAT
hepatobiliary only significant difference
NVP-od vs EFV, plt 0.001
15
Frank van Leth
Viramune is not licensed for once-daily dosing
in the UK
18
Deaths

• 25 patients died during the study
• 2 deaths attributed to NVP use
• female from Argentina with toxic hepatitis
  without evidence of
• hepatic co-infection
• Stevens Johnson syndrome from S. Africa. Died of
  MRSA septicaemia while recovering in hospital
• 1 death attributed to d4T use
• lactic acidosis
• 11 deaths related to HIV-disease
• 11 deaths non-Rx and non-HIV related
• none of suicides attributed to use of study
  medication

16
Frank van Leth
Viramune is not licensed for once-daily dosing
in the UK
19
Summary
NVP-od
NVP-bd
EFV
NVPEFV
significant
A
B
C
D
difference
n220
n387
n400
n209
Rx-success,
56.4
56.3
62.3
46.9
C vs D
pVLlt50 c/mL,
70.0
65.4
70.0
62.7
ns
3
CD4 increase, cells/mm
170
160
160
150
ns
grade 3/4 clinical AE,
15.0
20.4
18.0
24.4
A vs D
grade 3/4 liver associated lab AE,
13.2
7.8
4.5
8.6
A vs C
grade 3/4 other lab AE,
8.2
12.9
8.8
9.6
ns
Frank van Leth
Viramune is not licensed for once-daily dosing
in the UK
18
20
Change in Plasma Lipid Concentrations at 48 weeks
F. van Leth et al. Abstract 752. 10th Conference
on Retroviruses and Opportunistic Infections,
February 2003, Boston
21
Change in Plasma TCHDL-c ratio over 48 weeks
NVP vs EFV, plt0.001
F. van Leth et al. Abstract 752. 10th Conference
on Retroviruses and Opportunistic Infections,
February 2003, Boston
22
Change in Plasma HDL-c over 48 weeks
NVP vs EFV, plt0.001
F. van Leth et al. Abstract 752. 10th Conference
on Retroviruses and Opportunistic Infections,
February 2003, Boston
23
Change in Plasma Total Cholesterol over 48 weeks
ns
F. van Leth et al. Abstract 752. 10th Conference
on Retroviruses and Opportunistic Infections,
February 2003, Boston
24
Change in Plasma LDL-c over 48 weeks
ns
F. van Leth et al. Abstract 752. 10th Conference
on Retroviruses and Opportunistic Infections,
February 2003, Boston
25
Change in Plasma Triglycerides over 48 weeks
F. van Leth et al. Abstract 752. 10th Conference
on Retroviruses and Opportunistic Infections,
February 2003, Boston
26
2NN Conclusions

• 62.3 of patients receiving efavirenz vs. 56.3
  receiving NVP BID achieved treatment success at
  48 weeks
• NVP exhibited higher rates of clinical and/or
  laboratory hepatotoxicty
• EFV exhibited higher rates of grade 3-4
  CNS/psychiatric side effects (EFV 5.5 and NVP
  BID 3.6 and NVP QD 1.4)
• Two patients died from NVP-associated
  complications there were no deaths associated
  with EFV use
• NVP increased triglycerides to a smaller extent
  than EFV, and increased HDL cholesterol to a
  higher degree than that seen with EFV
• No significant difference in dislipidaemia
  between the arms

van Leth et al. 10th CROI, Boston MA, February
2003. Abs 176 752
27
What Pis?
28
BMS 008/044 24 week virological response
Murphy R et al. 10th CROI, Boston MA, February
2003. Abs 555
29
BMS 008/044 Median HDL level at 008 entry, 044
entry and 044 week 24
Murphy R et al. 10th CROI, Boston MA, February
2003. Abs 555
30
BMS 008/044 frequency of TC ?200mg/dl
Murphy R et al. 10th CROI, Boston MA, February
2003. Abs 555
31
BMS 008/044 frequency of LDL ?130mg/dl
Murphy R et al. 10th CROI, Boston MA, February
2003. Abs 555
32
NEAT 908 study Virologic response to lt50 c/ml
Per Protocol
84 83
55
ITT RDF
41
Per Protocol Stratified Difference (95 CI) -1
(-10, 7) ITT stratified Difference (95 CI)
15 (2, 28)
(PP) 908 n 150 134 130 120 116 111 NFV n
73 68 59 52 46 42
Nadler J et al. 10th CROI, Boston MA, February
2003. Abs 177
33
NEAT 908 study Drug-related adverse events of at
least moderate severity
No. () of Subjects
908 BID
NFV BID
With Adverse Event
N166
N83
Diarrhoea
8 (5)
15 (18)
Drug Hypersensitivity
15 (9)
4 (5)
Rash
12 (7)
2 (2)
Nausea
9 (5)
3 (4)
Vomiting
3 (2)
3 (4)
Fatigue
4( 2)
1 (1)
Headache
3 (2)
2 (2)
Insomnia
3 (2)
1 (1)
Weakness
3 (2)
1 (1)
Fisher Exact Test P 0.002
Nadler J et al. 10th CROI, Boston MA, February
2003. Abs 177
34
NEAT 908 study Fasting mean cholesterol (mg/dl)
HDL
LDL
Total
180
250
160
200
140
203
197
120
122
119
150
100
153
152
80
89
86
100
60
40
50
20
0
0
BL
Wk 48
BL
Wk 48
908 BID
NFV BID

Nadler J et al. 10th CROI, Boston MA, February
2003. Abs 177
35
Context 908r study

• 320 PI-experienced patients randomised to
• 908r 1400/200 OD
• 908r 700/100 BID
• LPVr 400/100 BID
• Baseline viral load CD4 were similar between
  arms
• Drug-related AEs (?Grade 2)
• 908r OD 19
• 908r BID 35
• LPVr BID 34
• 908r was non-inferior to LPVr
• Fewer patients achieved lt400 lt50 copies/ml on
  908r cf LPVr

DeJesus E et al. 10th CROI, Boston MA, February
2003. Abs 178
36
Tipranavir/ritonavir in PI-experienced patients

• 216 patients randomised to
• TPVr 500/100
• TPVr 500/200
• TPVr 750/200
• TPVr was not affected by up to 3 of the universal
  PI mutations (33, 82, 84, 90)
• Less inter-patient variability was seen with
  500/200
• 500/200 and 750/200 had similar antiviral
  activity
• 500/200 better tolerated than 750/200
• 500/200 selected for Phase III programme

Gathe J et al. 10th CROI, Boston MA, February
2003. Abs 179
37
BIKSLopinavir/r plus Efavirenz HIV RNA lt LOQ at
W16 and W24
HIV RNA log copies/ml W16 W16 W16 W24 W24 W24
HIV RNA log copies/ml N lt400 lt50 N lt400 lt50
Total 36 33 (92) 19 (53) 24 21 (88) 13 (54)
Naive 29 26 (90) 15 (52) 17 15 (88) 8 (47)
PI-experienced 7 7 (100) 4 (57) 7 6 (86) 5 (71)
Day0 gt5log 18 15 (83) 6 (33) 11 10 (91) 6 (55)
38
DAD study HAART and risk of myocardial
infarction
HAART use was associated with a 27 relative
increase in the rate of MI per year of exposure
over the first 7 years of use Absolute risk of MI
remains low
Friis-Moller N et al. 10th CROI, Boston MA,
February 2003. Abs 130
39
Antiretrovirals in development at 10th CROI

• Name Action Development stage
• GW4751 NNRTI In vitro
• GW4511 NNRTI In vitro
• GW3011 NNRTI In vitro
• RO033-4649 PI Phase I
• TMC114 PI Phase II
• PDPs Integrase In vitro
• AK602 Entry In vitro animal
• TAK-220 Entry In vitro animal
• UK-427,857 Entry In vitro
• TNX-355 Entry Phase I
• PA-457 Budding/maturation In vitro
• T-1249 Fusion Phase II
• Racivir (RCV) NRTI Phase I/II

Various. 10th CROI, Boston MA, February 2003. Abs
6, 7, 8, 9, 10, 11, 12, 13, 14, 14lb Otto MJ et
al. 10th CROI, Boston MA, February 2003. Abs 552
40
TMC114 Study design
Arasteh K et al. 10th CROI, Boston MA, February
2003. Abs 8
41
TMC114 Baseline PI susceptibility
Arasteh K et al. 10th CROI, Boston MA, February
2003. Abs 8
42
Median plasma-concentration time profiles of
TMC114 at day 14
Arasteh K et al. 10th CROI, Boston MA, February
2003. Abs 8
43
TMC114 plasma HIV-1 RNA results
Arasteh K et al. 10th CROI, Boston MA, February
2003. Abs 8
44
TMC114 clinical adverse events

• Most commonly reported were GI and CNS related
  events
• Diarrhoea 32
• Flatulence 18
• Headache 16
• Dizziness 11
• Events primarily mild/moderate in severity
• No dose relationship seen
• 2 discontinuations
• 1 GI CNS related events
• 1 oesophageal candidiasis
• 5 grade 3/4 Aes
• Primarily GI CNS 1 grade 4 rash
• One SAE - hepatotoxicity (TMC114r 600/100 BID
  group)

Arasteh K et al. 10th CROI, Boston MA, February
2003. Abs 8
45
T20- TORO 12 Demographics and Baseline
Characteristics
ENFOB OB (N661) (N334) Male (N,) 593
(90) 300 (90) White (N,) 590 (89) 296
(89) Age (median, years) 42 43 BL HIV-1 RNA
(median, log10 copies/ml) 5.2 5.1 BL CD4
(median, cells/mm3) 88 97 Prior ADEs (N, ) 523
(79) 286 (86) GSS at entry (mean)
1.7 1.8 PSS at entry (mean) 1.6 1.6
Genotypic and phenotypic sensitivity scores
(GSS and PSS) represent the number of drugs in
the regimen to which virus was sensitive,
excluding ENF.
46
Summary of patient characteristics at baseline
in TORO 1 and TORO 2

• Majority of patients white males in early 40s
• Viral load at baseline gt5 log10
• CD4 count at baseline 70 -100 cells/mm3
• Patients were heavily treatment-experienced
• Approximately 12 prior ARVs and 7 years on
  therapy

47
Summary of patient characteristics at baseline
in TORO 1 and TORO 2

• Patients had high levels of baseline resistance
  to antiretrovirals
• gt80 had 5 or more primary RT/PR mutations
• Approximately three quarters of patients had
  newly approved or investigational drugs in their
  OB regimen (LPV/r or TDF)
• Patients in TORO 1 and TORO 2 represent a heavily
  treatment-experienced population with significant
  drug resistance and limited treatment options

48
Summary of Results of the MainEfficacy Endpoints
(ITT Population)
Parameter ENFOB OB Trt 95CI p-value
(N661) (N334) Diff HIV 1 RNA
(log10 copies/ml) NA NA -0.846 -1.066,
-0.626 lt0.0001 LSM difference (ENFOB) OB CD4
T cells (cells/mm3 NA NA 36.6 20.7, 52.6
lt0.0001 LSM difference (ENFOB) OB HIV-1 RNA
lt50 copies/ml 15.9 6.3 2.99 1.81, 4.93
lt0.0001 responders HIV-1 RNA lt400
copies/ml 32.7 15.0 2.97 2.08, 4.23 lt0.0001
responders HIV-1 RNA ?1 log10
decrease 47.2 24.9 2.80 2.08, 3.77 lt0.0001
responders
NA not applicable. The method of the
meta-analysis used was based on the treatment
differences between ENFOB and OB alone from
TORO1 and 2. Therefore the individual estimate of
LSM is not available. Odds ratio
49
Demographic subpopulations Subgroup analysis of
mean change from baseline in log10 HIV-1 RNA at
week 24 (ITT population)
Non-
?
Male
Female
White
white
lt40yrs
40yrs
0
N38
N208
N300
N296
-1
Change from BL log10 HIV-1 RNA
N126
N34





N281
N593
N590
N71
N68
N380
-2
Plt0.05
50
Baseline viral load and CD4Subgroup analysis
of mean change from baseline in log10 HIV-1 RNA
at week 24 (ITT population)
lt40,000
40,000
CD4 lt100
CD4 100
?
?
copies/mL
copies/mL
cells/mm3
cells/mm3
0
N168
N262
-1
Change from BL log10 HIV-1 RNA

N72
N163

N347

N520

N141
-2
N314
ENF OB
OB
Plt0.05
51
Subgroup analyses by Genotypic Sensitivity Score
(GSS) (ITT, LOCF)
Genotypic Sensitivity Score
0
1
2
3
4
5
0
53
-0.5

95
112
Change from baseline log10 HIV-1 RNA
-1
21

93
61
-1.5
194
8


-2
p ? 0.05
108

174
17
-2.5
44
ENF OB N661
OB N334
Similar results observed with PSS
52
Treatment factorsSubgroup analysis of mean
change from baseline in log10 HIV-1 RNA at week
24 (ITT population)
53
Multiple regression analyses for change from
baseline to week 24 in log10 HIV-1 RNA data
(LOCF) ITT
Predictor RC 95 C.I. p-value Treatment with
ENF -0.89 -1.04, -0.74 lt0.0001 Baseline CD4
Count -0.20 -0.25, -0.15 lt0.0001 (per 100
cells/mm3) Baseline HIV-1 RNA -0.21 -0.33,
-0.08 0.0017(per log10 copies/ml) PSS (per unit
score) -0.26 -0.31, -0.21 lt0.0001 LPV/r in OB
-0.22 -0.36, -0.07 0.0037 Total Adherence
Score (per 10) -0.19 -0.24, -0.13 lt0.0001 Prio
r LPV/r Experience 0.83 0.69, 0.98 lt0.0001
Adherence based on 4 day recall Regression
Coefficient
54
TORO 2 Time to virological failure was
significantly delayed with T20 OB
1
0.75
ENFOB
1-Prob (Virological Failure)
0.5
OB
0.25
(Plt 0.0001)
0
0
4
8
12
16
20
24
Study Week
VF HIV-1 RNA lt 0.5 log10 decrease from BL on 2
consecutive visits, starting at Weeks 6 and 8 or
lt1.0 log10 decrease from BL on 2 consecutive
measurements, starting at Weeks 14 and 16
55
Percentage of most frequent adverse events (? 5
in either group)
NB bacterial Pneumonia 4.5
0.3 4.2
56
Eosinophilia (week 24)

• Eosinophilia
• x109 cells/L ENFOB
  OB
• N
  662 N 332
• 1-2 x ULN 55 (8.3) 5 (1.5)
• (gt 0.70 to ? 1.4)
• 2 x ULN 12 (1.8) 3 (0.9)
• (? 1.4)
• Total 67 (10.1) 8 (2.4)

• Eosinophilia was not associated with clinical
  events suggestive of hypersensitivity

57
Substitutions associated with T-20 resistance
cluster in the amino terminal heptad repeat (HR1)
of gp41
Amino Terminal Sequence of gp41
FLGFLGAAGSTMGARSMTLTVQARQLLSGIVQQQNNLLRAIEAQQHLLQL
TVWGIKQLQARILAVERYLKDQQ
Sites of amino acid substitutions associated with
T-20 resistance
58
T20 susceptibility of NL4-3 virus harbouring
gp41 single substitutions
aa 36-45 Substitution T20
Fold sequence EC50 (?g/ml)
change GIVQQQNNLL N/A
0.012 N/A GIVQHQNNLL Q40H
0.256 21 GIVQQQNDLL N43D
0.210 18 GIAQQQNNLL V38A
0.188 16 DIVQQQNNLL G36D
0.091 8 SIVQQQNNLL G36S
0.088 7 GIVQQQNSLL N43S
0.067 6 GIVQQQNKLL N43K
0.063 5 GIVQQQTNLL N42T
0.045 4 GIMQQQNNLL V38M
0.042 4 GIVQQQDNLL N42D
0.027 2 GIVQQQNNML
L44M 0.021 2 GIVQQQNNLM
L45M 0.017 1 GIVQQQENLL
N42E 0.015 1 GIVQQQSNLL
N42S 0.006 1
XI Intl. HIV Drug Resistance Workshop 2002.
Seville, Spain 1) Mink et al. Poster 22. 2)
Greenberg et al. Abstract 128
59
T20 susceptibility of NL4-3 virus harbouring
gp41 double substitutions
aa 36-45 Substitution T20
Fold sequence
EC50 (?g/ml) change GIEQQQSNLL V38E,
N42S 6.156 513 GIAQQQTNLL
V38A, N42T 1.782
149 GIAQQQDNLL V38A, N42D 1.685
140 GIVQQQTSLL N42T, N43S 0.727
61 SIMQQQNNLL G36S, V38M
0.424 35 GIVQQQTKLL N42T, N43K
0.388 32 SIVQQQNNML G36S,
L44M 0.181 15
XI Intl. HIV Drug Resistance Workshop 2002.
Seville, Spain 1) Mink et al. Poster 22. 2)
Greenberg et al. Abstract 128
60
T1249-102Percent of patients with ? 1.0 log
Decline (ITT)
100
80
63
60
50
rcent of Patients
40
29
20
Pe
0
5
8
11
Study Day
MissingFailure
61
Percent of patients with ? 1 log10 drop in HIV
RNA according to length of ENF therapy after VF
100
Median drop -1.6
90
80
70
Percent of patients with ? 1 log drop
60
50
Median drop -0.94
40
30
7/7
8/17
20
10
0
24-48 wk gt 48 wk
62
In the presence of drug pressure the GIA mutant
strain is fitter than the wild-type strain
1.0
Wt-PLAP 1071 W16-hisD
0.8
0.6
Fraction of population
0.4
0.2
0.0
0
2
4
6
8
10
12
14
Days post infection T20 5 µg/ml
Lu et al. XI Int. HIV Drug Resistance Workshop
2002. Seville, Spain Poster 67
63
STIs
64
CPCRA 064 STI in patients with multi-resistant
HIV

• 270 patients randomised to
• New regimen
• STI of 4 mths then new regimen
• Median baseline CD4 180 cells/µl
• Mean 2.75 active drugs available
• Study closed by DSMB
• STI did not appear to confer clinical,
  immunologic, virologic or QoL benefits

Lawrence J et al. 10th CROI, Boston MA, February
2003. Abs 67
65
GIGHAART Study Design

• - VL gt 50 000 cp/ml
• - CD4 lt 200/mm3
• - Prior TT ?2 PI
• ? 2 NRTIs
• ? 1 NNRTI

Deferred GIGHAART 8 weeks WASH-OUT
Immediate GIGHAART
D0
W12 Primary end point W20
W24 Follow -Up
W32
66
GIGHAART Therapy
D4T - DDI-AZT
3 - 4 NRTI
3TC - ABC
Hydroxyurea (HU) 500 mg bid

1 NNRTI NVP - EFV - DLV

3 PI
- RTV 400 mg bid

- IDV 400 mg bid
- APV 600 mg bid


- SQV 600 mg bid
or
- RTV 400 mg bid - LPV 400mg bid

- NFV 1250 mg bid

Optionnal since april 2000 From sept. 2000
67
Genotypic Resistance at Baseline
Immediate GIGHAART Deferred GIGHAART
n 33 n 29
72 86
88 94
RT gene - patients ? 3 TAMs - patients ? 1
NNRTI mut Protease gene- patients ? 1 major
mut.
97
91
68
ANRS 097 STI in salvage therapy

• 68 patients randomised to
• Gighaart (?7 drugs)
• STI of 8 weeks then gighaart
• Median baseline CD4 27 cells/µl
• Few/no available active drugs for gighaart
  regimen
• LPVr was only new drug for some patients
• STI followed by gighaart induces a significant
  virological and immunological benefit up to 48
  weeks

Katlama C et al. 10th CROI, Boston MA, February
2003. Abs 68
69
Partial STI

• Maintain Nukes only N15
• Leads to stable CD4 and VL for up to 6 months
• Less fit virus
• Little evolution further resistance
• Maintain PIs n5
• Rapid loss virological control

Deeks S CROI 2003
70
Immune-based therapies
71
Pegylated interferon alfa-2b in early stage HIV
Schugt I et al. 10th CROI, Boston MA, February
2003. Abs 59
72
Mycophenolate mofetil (MMF) addition to
HAARTn18 therapy-naïve HIV ve patients
MMF addition to a triple class HAART regimen
provided no additional benefit
Sankatsing S et al. 10th CROI, Boston MA,
February 2003. Abs 658a
73
New HIV Therapy

• Anton Pozniak
• Chelsea and Westminster Hospital
• London UK