Transcript 50 copies/mL - International AIDS Society

Welcome and
introduction
Pedro Cahn MD PhD
President International AIDS Society
President Fundación Huésped
Buenos Aires, Argentina
Agenda
Pedro Cahn
Individuals as patients: the importance of establishing a
therapeutic alliance
Sharon Walmsley
Initiating HAART: steering a course for long-term treatment
success
Jan van Lunzen
Demanding more in treatment-experienced patients:
maximising the chances of sustained undetectability
Panel discussion
Housekeeping
• Please ensure all mobile telephones are set to
silent mode
• Please use the question cards provided and
hand these in to the hostesses for the panel
discussion
Individuals as patients:
the importance of
establishing a
therapeutic alliance
Pedro Cahn MD PhD
President International AIDS Society
President Fundación Huésped
Buenos Aires, Argentina
The introduction of HAART marked a
turning point in HIV treatment
Mortality and frequency of use of combination ART
including a PI among HIV-infected patients with
CD4 <100 cells/mm3
30
100
80
Deaths
60
20
40
10
20
Use of PIs
0
0
1994
Palella et al. N Engl J Med 1998;338:853–860
1995
1996
1997
Therapy with a PI
(% of patient-days)
Deaths per 100
person-years
40
Risk of second virological failure has
declined dramatically
Incidence per 100 person-years
Incidence of second VF over time:
NA-ACCORD (n=33,381)
120
113.6
90
70.7
60
41.5
17.9
30
15.1
0
1996–97
1998–99
2000–01
*North American AIDS Cohort Collaboration on Research and Design
Deeks et al. 15th CROI, 2007, Boston, MA. Abstract 41
2002–03
2004–05
Maintaining HAART is still a challenge
Off all antiretrovirals
Any change to original HAART regimen, remaining on treatment
On original HAART regimen
100
Percentage
80
60
40
20
0
0
6
12
18
24
30
36
42
48
505
381
286
Months since starting HAART
n
1198
1108
1015
931
Mocroft et al. AIDS Res Hum Retroviruses 2005;21:743–752
822
665
New agents and new classes of antiretrovirals
have increased treatment options
Etravirine
NRTIs
NNRTIs
PIs
Fusion inhibitors
CCR5 inhibitors
Integrase inhibitors
1981
2000
2005
2006
2007
2008
2003
1998
1999
2000
2001
1995
1996
1997
1994
1991
1992
1987
1981
Maraviroc, raltegravir, elvitegravir
Darunavir
Tipranavir
Enfuvirtide, atazanavir, emtricitabine
Tenofovir
Lopinavir/r
Amprenavir
AIDS 1st reported
Efavirenz, abacavir
Nelfinavir, delavirdine
Ritonavir, indinavir, nevirapine
Lamivudine, saquinavir
Stavudine
Zalcitabine
Didanosine
Zidovudine
2008
How to select treatment in 2008?
Individualised treatment is key:
DHHS Guidelines January 2008
• “The Panel appreciates that HIV care is highly
complex and rapidly evolving. Guidelines are
never fixed and must always be individualized”
• “Individual tailoring is based on such
considerations as expected side effects,
convenience, comorbidities, interactions with
other required medications, and results of
pretreatment genotypic drug resistance testing”
DHHS panel on antiretroviral guidelines for adults and adolescents, Guidelines for the use of antiretroviral
agents in HIV-1 infected adults and adolescents. January 2008
Factors to consider when
individualising treatment
Comorbidities
Results of
resistance testing
Patient
adherence
potential
Pregnancy potential
Potential drug
interactions
Convenience
Potential adverse
drug effects
DHHS panel on antiretroviral guidelines for adults and adolescents, Guidelines for the use of antiretroviral
agents in HIV-1 infected adults and adolescents. January 2008
Prevalence of transmitted drug
resistance: WATCH
Percentage
0
3
6
9
12
Africa
15
NRTI
NNRTI
PI
Asia
Europe
North America
South America
Frentz et al. 6th European HIV Drug Resistance Workshop 2008, Budapest, Hungary
MDR
Multi-drug resistance in treatmentexperienced patients failing therapy
Estimated prevalence of triple-class antiretroviral drug
resistance (TC-DR) in 607 patients with genotype data obtained following
2 sequential HIV-RNA levels >1000 copies/mL
Prevalence of TC-DR
30
25
20
15
10
5
0
Overall
Non-HAART as first
HAART as first ART
(n=607)
ART (n=376)
(n=231)
TC-DR defined as having at least 1 mutation associated with reduced ART susceptibility for each of the 3 main
antiretroviral drug classes based on the IAS-USA guidelines excluding minor PI mutations
Napravnick et al. AIDS 2007;21:825–834
Age should also be considered
CDC reported a 5-fold increase in HIV infected people over age 50 (1990–2000)
US adults living with HIV/AIDS by age: CDC 2001–2005
100
4%
4%
5%
90
14%
15%
16%
5%
>60
50–59
18%
80
Percentage
6%
19%
40–49
30–39
70
60
37%
20–29
38%
39%
40%
40%
50
40
30
36%
34%
20
31%
28%
26%
10
10%
9%
9%
9%
9%
2001
2002
2003
2004
2005
0
CDC Annual Report 2005. Revised edition June 2007
Probability of surviving
Cumulative mortality rate for patients who
were not exposed to ART, according to age
group (<50 vs >50)
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
Younger patients
p<0.01
0
200
Older patients
400
Perez & Moore. Clin Infect Dis 2003;36:212–218
600
800
Time, days
1000
1200
1400
Probability of surviving
Cumulative mortality rate for patients who
were exposed to ART, according to age group
(<50 vs >50)
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
Older patients
p<0.29
0
200
Younger patients
400
Perez & Moore. Clin Infect Dis 2003;36:212–218
600
800
Time, days
1000
1200
1400
Reasons for changes to a first
HAART regimen
Reason
100
Unknown
Percentage
80
Other
60
Choice
40
Toxicities
20
0
Failure
1999
2000
2001
≥2002
Calendar year – starting HAART
n
Median CD4
Median VL
271
382
2.60
139
348
2.60
Mocroft et al. AIDS Res Hum Retroviruses 2005;21:743-52
138
355
2.60
78
336
2.72
p=0.36
p=0.37
HAART: not without toxicity
Dyslipidemia/CHD
Renal
Lipoatrophy
Bone density ?
Hepatic
Gastrointestinal
Specific toxicities associated with
treatment changes
Reasons for treatment changes in 140 changes due to toxicities
(virologically-suppressed patients)
Lactic acidosis
Raised amylases
Myositis
Headache
Lipid abnormality
Diabetes or raised glucose
Diarrhoea
Allergic reaction
Rash
Intolerance
Abnormal LFTs
CNS effects or insomnia
Peripheral neuropathy
Malaise or fatigue
Abdominal pain
Lipodystrophy
Anaemia
Nausea or vomiting
Renal problem
0
5
10
15
20
Frequency
Lodwick R et al. AIDS 2008;22:1039–1046
25
30
35
Cardiovascular risk: MI rates by age group in
HIV-infected and HIV-uninfected patients
Rates per 1000 person-years
Acute MI rates in 3851 HIV-infected and 1,044,589 HIV-uninfected
patients from 1996–2004: rate per 1000 person years
120
HIV infected
HIV uninfected
90
60
30
0
18–34
35–44
45–54
55–64
Age group (years)
Triant et al. J Clin Endocrinol Metab 2007;92:2506–2512.
65–74
75–84
SMART: Risk of major CVD events as
function of TI
Relative Hazard of Expanded CVD Events[1]
Patients With Major CVD Event (%)
Event
RR (TI/CT)
(95% CI)
P
Value
Clinical MI, silent MI,
CAD requiring
invasive procedure or
surgery, death from
CVD
1.57
(1.00-2.46)
.05
1.49
(1.04-2.11)
.03
TI
+ PVD, CHF, CAD
requiring drugs
1.58
(1.12-2.22)
.009
CT
+ unobserved death
from unknown cause
20
15
10
5
0
0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
Yrs From Randomization
TI
CT
2752
2720
1306
1292
713
696
379
377
10
10
Reproduced with permission from Phillips et al. Antiviral Therapy; 13: in press. ©2008 International Medical Press. All
rights reserved.
Prevalence of CVD risk factors in
D:A:D cohort
Family history of CHD
Previous CVD
Smoking
Hypertension
Obesity
Diabetes mellitus
Raised total cholesterol
Raised triglycerides
0
10
20
30
40
% of total D:A:D cohort
Friis-Moller et al. AIDS 2003;17:1179-1193
50
60
Prevalence of HCV and HBV infections in HIV
infected populations by HIV risk group
Patients positive (median %)
80
70
Anti-HCV
HBsAg
60
50
40
30
20
10
0
Total
Injection
drug use
Heterosexual
HIV risk group
Data from Western Europe and the USA
Alter et al. J Hepatol 2006;44:S6–S9
Homosexual
•
•
Bonn cohort (1990–2002)
• 285 HIV/HCV
co-infected patients
Liver-related mortality rates
per 100 person-years
• HAART: 0.45
• ART: 0.69
• No therapy: 1.70
Predictors for
liver-related mortality
• No HAART
• Low CD4 cell count
• Increasing age
Overall mortality
1.0
HAART*
0.8
0.6
ART
0.4
No therapy
*p<0.001
0.2
0
1000
2000
3000
5000
6000
Liver-related mortality
1.0
HAART*
ART
0.8
No therapy
0.6
0.4
*p=0.018
0.2
0
1000
2000
3000
Days
Qurishi et al. Lancet 2003:362:1708–1713
4000
Days
Cumulative survival
•
Cumulative survival
HAART reduces overall liver mortality
in HIV/HCV-coinfected patients
4000
5000
6000
HIV-infected patients in the HAART era have a
10-year shorter expected survival than ageand gender-matched controls
Survival from age 25 years
Probability of Survival
1
Population controls
0.75
Late HAART
(2000-2005)
0.5
Early HAART
(1997-1999)
0.25
0
Pre-HAART (1995-1996)
25
30
35
40
45
50
Age, y
Adapted from Lohse et al. Ann Intern Med 2007;146:87-95
55
60
65
70
Women of child-bearing age
• “In women of reproductive age, antiretroviral
regimen selection should account for the
possibility of planned or unplanned pregnancy”
DHHS panel on antiretroviral guidelines for adults and adolescents, Guidelines for the use of antiretroviral
agents in HIV-1 infected adults and adolescents. January 2008
Treatment options in HIV-infected
pregnant women: DHHS guidelines 2008
Recommended
Alternative
Not recommended
NNRTIs
NVP
EFV
DLV
Protease inhibitors
LPV/r
IDV
RTV
SQV/r
NFV
(insufficient data: APV,
ATV, DRV, fAPV, TPV)
NRTIs
AZT
3TC
ddl
FTC
d4T
ABC
(Insufficient data TDF)
Enfuvirtide, maraviroc: insufficient data to recommend
DHHS panel on antiretroviral guidelines for adults and adolescents, Guidelines for the use of antiretroviral
agents in HIV-1 infected adults and adolescents. January 2008
Considerations for treatment of HIV
in children
Product
Recommended dosing for
paediatric populations?
Paediatric formulation
available?
Delavirdine

Efavirenz

Nevirapine




















NNRTI
PI
Amprenavir
Atazanavir
Darunavir
Fosamprenavir
Lopinavir/r
Nelfinavir
Saquinavir
Tipranavir
Tipranavir US PI, 2008. Drugs used in the treatment of pediatric HIV infection: http://fda.gov/oashi/aids/pedlbl.html
Alliance in the guidelines
• DHSS guidelines 2008
• “Achieving treatment goals requires a balance of
sometimes competing considerations”
• “Providers and patients must work together to
define priorities and determine treatment goals
and options”
DHHS panel on antiretroviral guidelines for adults and adolescents, Guidelines for the use of antiretroviral
agents in HIV-1 infected adults and adolescents. January 2008
HAART: the new targets
• The 1st decade: preservation of CD4 levels in
order to decrease AIDS-related morbidity and
mortality
• The 2nd decade: maximize virological
suppression in order to avoid emergence of
resistance mutations
• The 3rd decade: to expand life expectancy by
decreasing “non-AIDS related” morbidity and
mortality
Summary
• Individualised therapy should be based on a
range of often interdependent factors
• For optimum outcomes, providers must work
together with HIV-infected individuals to define
priorities and determine treatment options
• This can be facilitated if a strong therapeutic
alliance has been established
Initiating HAART:
steering a course for
long-term treatment
success
Sharon Walmsley MD
Professor of Medicine
University of Toronto
Senior Scientist
Toronto General Hospital
Research Institute
Considerations for initiating HAART
Suitability
for use in
special patient
groups
Efficacy/
durability
Metabolic profile/
CV risk
Genetic barrier
to resistance
Adherence/
pill burden
Short and long-term
tolerability
Initial HAART for naïve patients:
NNRTI-based vs PI-based regimens
• ACTG51421
• Efavirenz (EFV) + 2 NRTIs vs lopinavir-ritonavir (LPV/r) + 2
NRTIs vs LPV/r + EFV
• n=753
• Primary endpoints:
• Time to virological failure
• Time to regimen failure
• FIRST2
• NNRTI + 2 NRTI vs PI + 2 NRTI vs PI + NNRTI + 1 NRTI
• n=1397
• Primary endpoint:
• Composite of an AIDS-defining event, death or CD4 cell count
decline to <200 cells/mm3
1. Riddler SA et al. NEJM 2008;358:2095–2106; 2. MacArthur RD et al. Lancet 2006;368:2125–2135
NNRTI vs PI-based strategies:
virological response
Patients with HIV-RNA <50 copies/mL (%)
ACTG51421
FIRST2
100
100
90
90
80
70
70
60
50
EFV vs LPV/r at week 96:
p=0.003
40
30
EFV
LPV/r
20
% patients
% patients
80
60
50
Time to reduction varied
significantly among treatment
strategies: p<0.0001
40
30
NNRTI
PI
20
10
10
0
0
0 4 8 16 24 32 40 48 56 64 72 80 88 96
0
Weeks since randomisation
EFV 250 236
LPV/r 253 235
NRTI- 250 242
sparing
224
226
228
212
217
217
201
201
206
1
2
3
4
5
6
30
17
17
5
2
2
Years from randomisation
178
177
180
PI: 466
NNRTI: 458
PI+NNRTI: 459
179
113
120
118
74
77
89
60
47
56
42
31
Modified from: 1. Riddler SA et al. NEJM 2008;358:2095–2106 and 2. MacArthur RD et al. Lancet 2006;368:2125–2135
Initial HAART for naïve patients: NNRTI-based
vs PI-based regimens – main findings
• PI regimens inferior to NNRTI regimens in
terms of achieving and maintaining virological
suppression
• Rate of AIDS-defining events, death or severe
immunologic decline comparable
MacArthur RD et al. Lancet 2006;368:2125–2135; Riddler SA et al. NEJM 2008;358:2095–2106
ARTEN: NVP vs atazanavir/r in combination
with emtricitabine (FTC)/tenofovir (TDF)
Genotype report
Day -28
Week 2:
up-titration to 400 mg NVP/day
Screening
(n=187)
Nevirapine BID + FTC/TDF
Cont
or new
Screening
(n=187)
Nevirapine QD + FTC/TDF
Cont
or new
Screening
(n=187)
Atazanavir/r + FTC/TDF
Cont
or new
0
12
DSMB
200 pat
48
Primary
endpoint
Fully recruited; ongoing
144
or EOT
Post-trial
Factors to consider when choosing the NNRTI
Efficacy/
durability
Long-term safety/
tolerability
Metabolic profile/
CV risk
Suitability for use in
special patient groups
2NN: randomized controlled trial comparing
virological efficacy of nevirapine and efavirenz
Percentage of patients with viral load (VL)
<50 copies/mL through 48 weeks (ITT)
100
p=ns for all pairwise
comparisons
90
% patients
80
70
65.4
70
70
NVP QD (n=220)
EFV QD (n=400)
60
50
40
30
20
10
0
NVP BID (n=387)
van Leth F et al. Lancet 2004;636:1250–1253
2NN: virological efficacy of nevirapine and
efavirenz: long-term follow up
Percentage of patients with VL <400 copies/mL
through 144 weeks
100
90
87
91
87
% patients
80
70
60
50
40
30
20
10
0
NVP BID (n=224)
NVP QD (n=120)
Wit F et al. 4th IAS 2007, Sydney, Australia. Abstract WEPEB032
EFV QD (n=223)
Durability of NVP-based regimens in switch
patients: 3-year follow-up of NEFA
Proportion of non-failing patients*
Kaplan-Meier survival estimates
1.00
NVP
EFV
Abacavir
0.75
0.50
0.25
0.00
0
1
*Failure = death, progression to AIDS or virological failure
Martinez E et al. AIDS 2007;21(3):367–369
Years
2
3
Subanalysis of BICOMBO study:
NVP vs EFV in combination with once-daily
Kivexa® or Truvada®
Study population (n=335)
• Stable lamivudine-based regimen for ≥6 months (VL <200)
NRTI switch to Kivexa®
NRTI switch to Truvada®
Primary analysis, week 48
• Randomization stratified according to the third drug, either a PI (n=33) or a NNRTI (n=300)
• Patients treated with NVP (n=118) compared versus patients treated with EFV (n=182)
Martinez E et al. 17th IAC 2008. Abstract TUPE0110
Treatment and virological failure: subanalysis
of BICOMBO study
Primary endpoint: the proportion of patients with treatment failure
for any reason through week 48
100
90
Treatment failure
Virological failure
80
% patients
70
60
50
40
30
n=24
n=27
20
10
n=2
n=2
0
Nevirapine
p=0.271 for Therapeutic Failure (Fisher’s exact test)
p=0.647 for Virological Failure (Fisher’s exact test)
Martinez et al. 17th IAC 2008. Abstract TUPE0110
Efavirenz
Factors to consider when choosing the NNRTI
Efficacy/
durability
Long-term safety/
tolerability
Metabolic profile/
CV risk
Suitability for use in
special patient groups
Nevirapine: hepatic events are
related to gender and CD4 count in
treatment-naïve individuals
% patients with symptomatic
hepatic events
12
<150 cells/µL
150–250 cells/µL
250–400 cells/µL
8
4
0
Females
Males
Stern JO et al. XIVth International AIDS Conference 2002, Barcelona, Spain. Abstract LBOr15
Reanalysis of the 2NN study: hepatic events
in those meeting CD4+ criteria*
Asymptomatic hepatic event after NVP
Symptomatic hepatic event after NVP
Asymptomatic event after EFV
Symptomatic event after EFV
20
16
% hepatic events
p=ns
12
p=ns
8
4.2
4
2.8
3.9
3.2
3.9
3.6
0
NVP QD
119
n=
NVP BID
255
Storfer S et al. EACS 2005, Dublin, Ireland. Abstract PE9.6/2
EFV
225
*Excluding Thai centre
What about virologically suppressed patients
who switch to nevirapine?
• Meta-analysis of randomised controlled trials including:
• Virologically suppressed patients who switched to NVPcontaining HAART with 3 month follow up
• CD4 counts classified as high (HCD4; 400 cells/µL for males
and 250 cells/µL for females) or low (LCD4)
• Primary endpoint: hepatotoxicity within 3 months of switch
• Randomised control trials included:
•
•
•
•
NEFA (n=155, minimal follow-up 36 months)
GESIDA (n=101, minimal follow-up 3 months)
QDLluita (n=84, minimal follow-up 12 months)
Boehringer Ingelheim study 1100.138 (n=70, minimal
follow-up 24 months)
De Lazzari E et al. HIV Med 2008;9:221–226
What about virologically suppressed patients
who switch to nevirapine?
Development of hepatotoxicity or rash within
3 months of switch
% patients
40
35
Low CD4+ count (n=133)
30
High CD4+ count (n=277)
25
20
13
15
10
10
5
2
4
0
Hepatotoxicity
De Lazzari E et al. HIV Med 2008;9:221–226
Rash
What about virologically suppressed patients
who switch to nevirapine? Data from ATHENA
• 3752 patients classified in the following groups:
Naïve patients
Pretreated patients
Low CD4+ count
pre ART (PL)
Low CD4+
count at
start NVP
(NL; 77%)
High CD4+
count at
start NVP
(NH; 23%)
Low CD4+
count at
start NVP
(PLL; 49%)
High CD4+
count at
start NVP
(PLH; 30%)
High CD4+ count
pre ART (PH)
Low CD4+
count at
start NVP
(PHL; 4%)
• Rates of discontinuation due to rash and hepatotoxicity
calculated and compared between groups
Wit F et al. Clin Infect Dis 2008;46:933–940
High CD4+
count at
start NVP
(PHH; 17%)
ATHENA: risk of rash and hepatotoxicity in
patients with undetectable HIV RNA who
switch to nevirapine
Odds ratio (adjusted)
5
4
3
2
1
0
NL
NH
Naïve patients
PLL
PLH
Experienced patients
Wit F et al. 4th IAS 2007, Sydney, Australia. Abstract MOPEB008
PHH
Conclusions: impact of CD4+ count on rash
and hepatotoxicity in switch patients
• In meta-analyses, baseline CD4 count/gender
is not associated with increased risk of
rash/hepatotoxicity on switching to NVP in
virologically suppressed patients1
• Supported by data from ATHENA2 and
EUROSIDA3 suggesting risk similar in naïve
and treatment-experienced patients with
undetectable viral load
1. De Lazzari E et al. HIV Med 2008;9:221–226; 2. Wit F et al. Clin Infect Dis 2008;46:933–939;
3. Mocroft A et al. Antivir Ther 2007;12:325–333
Toxicities as a reason for treatment changes
• Reasons for treatment change assessed in
virologically-suppressed patients (n=508; 912
person-years follow-up)
• Reason for change available in 279 changes
• Most common reasons:
• Toxicity: 50.2%
• Patient choice: 17.6%
• Poor adherence: 3.6%
Lodwick R et al. AIDS 2008;22:1039–1046, Royal Free London, 2000-2005
Toxicities as a reason for treatment changes
Specific toxicities associated with
treatment changes
Lactic acidosis
Raised amylases
Myositis
Headache
Lipid abnormality
Diabetes or raised glucose
Diarrhoea
Allergic reaction
Rash
Intolerance
Abnormal LFTs
CNS effects or insomnia*
Peripheral neuropathy
Malaise or fatigue
Abdominal pain
Lipodystrophy
Anaemia
Nausea or vomiting
Renal problem
0
5
10
15
20
25
30
35
Frequency
*CNS effects comprised 23% of the total toxicities and all reports were in patients taking EFV
Lodwick R et al. AIDS 2008;22:1039–1046
Long-term CNS toxicity with efavirenz use
Cross-sectional study from one university hospital outpatient clinic – patients
receiving stable EFV-based regimen for at least 1 year
Neuropsychiatric adverse events with
efavirenz treatment (mean treatment
duration: 91.1 ± 39.5 weeks, n=60)
50
% of patients
40
30
20
10
0
Dizzy
Sad
Mood
changes
Irritable Impaired Abnormal
concentration dreams
Modified after Fumaz C et al. J Acquir Immune Defic Syndr 2005;38(5):560–565
Switching from efavirenz to nevirapine
leads to resolution/improvement of
neuropsychiatric side effects
18 patients with
sleep disturbances
20 patients with
neuropsychiatric
side effects
Switch from efavirenz
to nevirapine
14 pts
symptoms
resolved
completely
6 pts
reported
significant
improvements
Switch from efavirenz to nevirapine
14 pts
symptoms
resolved
completely
Ward D & Curtin J. AIDS Patient Care STDS 2006;20(8):542–548
3 pts
reported
improvement
1 pt
had no
change
Factors to consider when choosing the NNRTI
Efficacy/
durability
Long-term safety/
tolerability
Metabolic profile/
CV risk
Suitability for use in
special patient groups
D:A:D study: adjusted relative rates of MI
according to cumulative exposure to PIs
and NNRTIs
Protease inhibitors
Non-nucleotide reverse-transcriptase inhibitors
Adjusted relative rate
8.0
4.0
2.0
1.0
0.5
0
<1
1–2
2–3
3–4
Exposure (year)
Modified from Friis-Møller N et al. N Engl J Med 2007;356:1723–1735
4–5
5–6
>6
Interruption of ART and risk of cardiovascular
disease (CVD): findings from SMART
ARV therapy
(on at baseline)
HR for CVD events
(DC/VS*)
95% CI (p-value)
Any ARV
1.57
1.00–2.46 (0.05)
NNRTI based
1.37
0.85–2.21 (0.20)
NVP based
9.29
1.19–72.6 (0.05)
*DC, drug conservation (STI), VS, virological suppression (no STI)
Phillips A et al for the SMART Study Group. 14th CROI 2007, Los Angeles, USA. Abstract 41
Metabolic abnormalities and risk of MI
Unadjusted model
Multivariable Poisson model adjusted for age, sex, BMI, HIV risk, cohort,
calendar year, race, family hx CVD, smoking, previous CVD event, TC, HDL,
HTN, DM
Total cholesterol (per mmol/L incr)
RR: 1.31* (1.25–1.37)
Total cholesterol (per mmol/L incr)
RR: 1.26* (1.19–1.35)
Triglycerides (per 2-fold incr)
RR: 1.58* (1.43–1.75)
Hypertension
RR: 1.30† (0.99–1.72)
HDL (per mmol/L incr)
RR: 0.72‡ (0.52–0.99)
0.1
0.5
1
Relative rate of MI (95% CI)
*p<0.001; † p=0.06; ‡ p=0.05
Friis-Møller N et al. N Engl J Med 2007;356:1723–1735
5
10
NNRTI comparison of lipid changes: data
from the 2NN study
HDL-cholesterol
TC:HDL-C ratio
NVP
EFV
5.0
TC:HDL-C
HDL-C mmol/L
1.5
1.0
0.5
4.5
4.0
3.5
3.0
0 2 4 8 12
24
36
48
Weeks after start allocated treatment
Van Leth F et al. PLoS Med 2004;1:e73
0 2 4 8 12
24
36
48
Weeks after start allocated treatment
Switching from PI to nevirapine has a
favourable effect on lipid profile: LIPNEFA
study (24 months)
Percentage change (%)
(Median, 24 months from baseline)
Total
cholesterol
LDL
HDL
Triglycerides
cholesterol cholesterol
40
34
30
18
20
10
0
-10
5
-3
-7
-11
-20
-30
-40
2
0
NVP (n=29)
EFV (n=32)
ABC (n=29)
Fisac C et al. AIDS 2005;19:917–925
-8
-12
-14
-28
Switching from efavirenz or PI to nevirapine
has a beneficial effect on lipids
Median change in plasma lipid levels
from baseline to 36 months (mg/dL)
Prospective 3-year observational cohort study
Patients switched from EFV- (n=44), or PI-containing regimens (n=105)
20
10
0
-10
-20
-30
-40
-50
LDL-C
Goldbach R et al. 17th IAC 2008. Abstract TUPE0071
HDL-C
TG
Nevirapine intensive lipid evaluation
(NILE) study
• Nevirapine exerts favourable changes on the plasma
lipid profile, especially on HDL cholesterol
• The NILE study looked at the mechanisms of how
nevirapine influences lipids
• Patients with HIV-RNA ≤50 copies/mL while on
AZT/3TC/ABC for ≥6 months and no prior NNRTI
exposure (n=13) had NVP added
Sankatsing R et al. 4th IAS 2001, Sydney, Australia. Poster WEPEB032
NILE study: mechanism of lipid changes
with nevirapine
HDL
*p<0.05 for
% change from
week 0 to 24
*
*
Large HDL
particles
*
*
*p<0.05 for
% change from
week 0 to 6
*
*
Apo A-1
Cholesteryl ester
transfer protein
activity
-10
*p<0.05 for
% change from
week 6 to 24
*
0
10
Week 6
Week 24
*
20
30
% change from baseline
Sankatsing R et al. 4th IAS 2001, Sydney, Australia. Poster WEPEB032
40
50
Metabolic impact of ARV drugs/drug classes
Metabolic impact of drug classes
Less
Metabolic impact of drugs
Less
More
More
NNRTI
NRTI
PI
NVP
3TC/FTC
ABC
TDF
fAPV
EFV
ZDV
ATV/r
SQV/r
ddl
LPV/r
fAPV/r
DRV/r
d4T
IDV/r
TPV/r
RTV (full dose)
Lundgren J et al. HIV Med 2008;9:72–81. EACS guidelines
Association between HAART and
fibrinogen levels
• Fibrinogen is an inflammatory factor associated with
atherosclerosis
• Framingham study: each SD increase in fibrinogen level
(56 mg/dl) is associated with a 20% independent increment of
risk for cardiovascular disease
• Cross-sectional analysis of 1131 HIV-infected
participants and 281 controls with
fibrinogen measurements
• Median fibrinogen levels higher in HIV-infected individuals
compared with controls
• Associations between current use of each drug and
drug class and fibrinogen levels assessed by
multivariable linear regression
Madden E et al. AIDS 2008;22:707–715. CARDIA: substudy of Fat Redistribution And Metabolic change in HIV
infection (FRAM)
Fibrinogen levels with different antiretroviral agents
Median fibrinogen
(mg/dL) ±95% CI
450
400
p<0.0001
p<0.0001
† p<0.0001 vs no NNRTI
* p=0.0002 vs no NNRTI
*
†
350
300
0
No PI
All PI
(n=512) (n=616)
No
All
NNRTI NNRTI
(n=695) (n=433)
Modified from Madden E et al. AIDS 2008;22:707–715
NVP
(n=148)
EFV
(n=273)
Factors to consider when choosing the NNRTI
Efficacy/
durability
Long-term safety/
tolerability
Metabolic profile/
CV risk
Suitability for use in
special patient groups
Stage of liver fibrosis and levels
of antiretrovirals
Plasma levels in 279 HIV/HCV + pt on HAART
Liver fibrosis (Fibroscan); 37% F0–F1, 15% F2, 11% F3, 37% F4
Drug plasma levels (ug/ml)
•
•
12
10
8
p<0.01
6
4
2
0
n=
•
Cirrhotic patients
No
Yes
EFV
NVP
LPV
30 16
31 15
33 23
ATV 400 ATV 300
36 22
48 25
In compensated cirrhotics plasma levels of NNRTI, mainly EFV, may be increased,
plasma levels of PI remain similar to non-cirrhotics
Barreiro P et al. J Infect Dis 2007;195:973–979
Association between NNRTI and PI exposure
and liver fibrosis progression
• Objective: to analyse the effect of exposure to
NNRTI and PI on liver fibrosis progression in
HIV/HCV coinfected patients (n=201)
• Fibrosis stage score (F) was recorded from 0 (no
fibrosis) – 4 (definite cirrhosis)
• Fibrosis progression rate (FPR) was also calculated
by dividing F by the estimated duration of HCV
infection in years.
• Exposure to HAART reduced FPR and
development of bridging fibrosis and cirrhosis
Berenguer J et al. Clin Infect Dis 2008;46:137–143
Association between NNRTI and PI exposure
and liver fibrosis progression
AOR; P value
1.32; 0.020
1.24; 0.057
1.64; 0.003
1.32; 0.033
1.72; 0.008
F1 vs F3
HAART
PI
NNRTI
Efavirenz
Nevirapine
0.7 0.8 0.9 1
2
3
Harmful Beneficial
F2 vs F3
AOR; P value
1.20; 0.131
1.00; 0.990
1.51; 0.016
1.42; 0.091
1.58; 0.025
HAART
PI
NNRTI
Efavirenz
Nevirapine
0.7 0.8 0.9 1
Harmful Beneficial
Berenguer J et al. Clin Infect Dis 2008;46:137–143
2
3
AOR = adjusted odds ratio
Women of childbearing age (WCBA)
• The number of HIV positive women
is increasing
• With increased life expectancy, more
positive women are having children
• Family planning and open physician – patient
dialogue are necessities
• Treatment must be safe for both planned
and unplanned pregnancies
Nearly half of pregnancies are unintended
Finer L & Henshaw S. Perspect Sex Reprod Health 2006;38:90–96
FDA pregnancy categories for NNRTIs
 Upgrade of nevirapine to pregnancy category B
Category B Animal reproduction studies have failed to
demonstrate a risk to the fetus and there are
no adequate and well controlled studies in
pregnant women
Nevirapine
Category D There is positive evidence of human fetal risk
Efavirenz
based on adverse reaction data from
investigational or marketing experience or
studies in humans, but potential benefits may
warrant use of the drug in pregnant women
despite potential risks
Nevirapine AUC (µg*hr/mL)
Pregnancy does not alter NVP PK
160
140
120
100
80
60
40
20
0
2nd trimester
3rd trimester
Postpartum
Mean NVP AUC (n=26 patients)
– Antepartum: 56±13 µg*h/mL
– Postpartum: 61±15 µg*h/mL
Capparelli E et al. HIV Med 2008;9:214–220
What is the effect of pregnancy on the
development of liver enzyme elevations/rash?
• Objective:
• To assess predictors of developing liver enzyme elevations
and rash in pregnant and non-pregnant women initiating
HAART (total cohort n=612; total pregnancies n=146)
• Included 79 pregnant women and 61 non-pregnant women
on NVP
• Patients on NVP versus non-NVP regimens compared
• Analyses stratified by baseline and nadir CD4 count
and pregnancy status
• Conclusions
• Pregnancy was not an independent risk factor for developing
liver enzyme elevations or rash in patients receiving NVP
Aaron et al. 15th CROI 2008, Boston, USA. Poster 983
Factors to consider when choosing the NNRTI
Efficacy/
durability
Proven
Long-term safety/
tolerability
Metabolic profile/
CV risk
Favourable
Favourable
lipid profile
Suitability for use in
special patient groups
NNRTI of choice
in WCBA
Demanding more in
treatment-experienced
patients:
maximising the chances of
sustained undetectability
Jan van Lunzen MD PhD
Associate Professor of Medicine
Medical Director
Infectious Diseases Unit
University Medical Center
Hamburg-Eppendorf
2006/2007 guideline paradigm shift for
treatment-experienced patients
‘Goal for all patients
is to achieve an
undetectable viral load’
DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, 2008; IAS-USA Panel.
Treatment for Adult HIV Infection. Recommendations of the IAS-USA Panel 2006
Durable virological suppression was >2
times more common with TPV/r vs CPI/r
Proportion of patients in the RESIST studies with
VL <50 copies/mL (ITT NCF)
40
% VL <50 copies/mL
35
TPV/r: n=746
CPI/r: n=737
30
25
23.2
22.8
20.6
20
15
13.9
11.1
10
9.1
10
6.5
5
0
n=170 n=82
n=82
24
n=173
n=74
n=154 n=67
n=67
48
96
Weeks
Data on file
n=104
n=48
n=48
156
Durable efficacy was achieved with comparable
overall tolerability: RESIST 156 weeks
TPV/r
CPI/r
Any grade 3–4 adverse event
(per 100 PEY)
25.9
28.9
Serious adverse events
(per 100 PEY)
20.0
22.2
Discontinuation of study
medication due to adverse
events (per 100 PEY)
9.4
6.8
PEY, patient exposure years
Hicks C et al. 11th EACS 2007, Madrid, Spain. P7.3/25
Ritonavir plasma levels with
different PIs
Mean RTV trough concentration
(µg/mL)
0.7
0.6
0.589
0.5
0.4
0.324
0.3
0.247
0.183
0.2
0.1
0.0
SQV/r
LPV/r
TPV/r
APV/r
Sabo JP et al. 7th International Workshop on Pharmacology in HIV Therapy 2006, Lisbon, Portugal. Poster 43
Comparable rates of GI side effects:
RESIST week 156
100
% of patients
80
TPV/r
CPI/r
60
40
34.7
31.2
22.7
20
19.3
14.7
10.2
0
n=1486
Data on File
Diarrhoea
Nausea
Vomiting
Action & outcome of liver enzyme elevations with
TPV/r at 96 weeks (Phase IIb and III studies)
1299 patients treated with TPV/r
Discontinued
31/1299 (2.4%)
144 (11.1%) G3/4 ALT/AST
Continued without
interruption
93/144 (65%)
Temporary
interruption/restart
28/144 (19.4%)
ALT/AST ≤G2
88/93 (94.6%)
ALT/AST ≤G2
17/28 (60.7%)
Pol S et al. 11th EACS 2007, Madrid, Spain. Poster P4.5/03
Discontinued
31/144
(21.5%)
% VL <50 copies/mL
(ITT NCF)
Durable efficacy and tolerability in treatmentexperienced children and teenagers
Response on TPV/r oral solution (OS) or capsules + OBR
in different age-groups
60
Week 24
Week 48
Week 100
50
40
30
20
10
0
2–5 y, OS
(n=25)
6–11 y, OS
(n=37)
12–18 y, OS
(n=24)
12–18 y,
capsules
(n=29)
• Most frequently reported AEs: GI events (majority were mild)
• Only 13.9% discontinued TPV/r due to AEs
Salazar JC et al. 17th IAC 2008, Mexico. Poster MOPE0187
How to use TPV/r in clinical practice?
Early virological response (at week 8)
% of patients with VL <50 copies/mL
at week 48 (ITT)
50
41.6
40
30
20
10
4
0
<1.5
≥1.5
Week 8 VL reduction (log10 copies/mL) ITT
Ernst J et al. 4th IAS 2007, Sydney, Australia. Poster WEPEB037
2006/2007 guideline paradigm shift for
treatment-experienced patients
‘Goal for all patients
is to achieve an
undetectable viral load’
‘Resistance testing
should be performed
to assist in selecting active
drugs in case
of virologic failure’
DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, 2008; IAS-USA Panel.
Treatment for Adult HIV Infection. Recommendations of the IAS-USA Panel 2006
Understanding resistance testing
• Interpretation of resistance test results requires
knowledge of the mutations that different
antiretroviral drugs select for and of the
potential for cross resistance to other drugs
conferred by certain mutations
DHHS Guidelines January 2008
Development of the weighted score
• Why was a new score developed and why is
it weighted?
• Some mutations known to be more important than others
• Some mutations not in TPV score are associated with
increased susceptibility to TPV
• Goal was to develop a score to better predict
virological response to TPV/r
• Provide clinicians with additional information regarding which
mutations have the largest impact on virological response
TPV weighted mutation score:
weight classification
Weight
range
Class
Increased
response
Minor
mutations
Major
mutations
Score
Mutations
<0
24I, 50L/V, 54L, 76V
1–2
10V, 36I, 43T, 46L, 84V
≥3
47V, 54A/M/V, 58E, 74P, 82L/T, 83D
Response
≤3
>3–≤10
>10
Susceptible (S)
Partially susceptible (PS)
Resistant (R)
Scherer J et al. 11th EACS 2007, Madrid, Spain. Poster P3.4/07
Virological response by weighted
score: RESIST
Resistant
Partially susceptible
Susceptible
80
Responders* (%)
70
60
50
40
30
20
10
0
Week 8
Week 24
Week 48
Total n=745
*Response defined as VL reduction ≥1 log10 below baseline without treatment change
Scherer J et al. 11th EACS 2007, Madrid, Spain. Poster P3.1/12
Increased and durable response to TPV/r when
>1 hypersusceptibility mutations are present
Response rates in RESIST TPV/r patients*
No increased susceptibility mutations
1 increased susceptibility mutation
>1 increased susceptibility mutation
100
Response rate (%)
90
80
70
60
50
Hypersusceptibility mutations:
40
24I, 50L/V, 54L, 76V
30
20
10
0
Odds ratio for
response 0 vs >1
Week 8
-1.5 log10 copies/mL
3.1
Hall et al. XVII IHDRW 2008, Sitges, Spain. Abstract 124
*Background activity score (BAS) >0.5
Week 48
<50 copies/mL
2.5
Case study
•
•
•
•
•
•
•
Gender:
Age:
Ethnic origin:
Risk of infection:
Date of infection:
Date of first dose:
CDC stage:
male
76 years
German
MSM
unknown
1987
C3
Case study
Past medical history:
• Hepatitis B
• 1988 OHL, oral thrush
• 1989 herpes zoster
• 1995 microsporidiosis
• 1998 recurrent condyloma
• 2000 HIV nephropathy
• 2001 syphilis, recurrence 2005
• 2004 severe lipodystrophy
• 2006 candida oesophagitis
AZT, DDC, SQV, 3TC, d4T, IDV, SQV/RTV, NFV/RTV, NVP, IFα, ABC, IDV/RTV, APV/NFV, LPV/r, EFV, DVD, TFV, T20
500
6.00
5.00
350
4.00
300
250
3.00
200
2.00
150
100
1.00
CD4
HIV RNA
Nov-04
Nov-03
Sep-03
2002
2001
2000
1999
1998
1997
1996
1995
1994
0
1992
50
1991
CD4 (cells/µL)
400
0.00
HIV RNA (cop/mL)
450
November 2004
VL 2950/mL, CD4 127/µL
ART: TVF,DDI,LPV/r,SQV,T20
500
6.00
5.00
350
4.00
300
250
3.00
200
2.00
150
100
1.00
CD4
HIV RNA
Nov-04
Nov-03
Sep-03
2002
2001
2000
1999
1998
1997
1996
1995
1994
0
1992
50
1991
CD4 (cells/µL)
400
0.00
HIV RNA (cop/mL)
450
PI: 10I, 48L, 50V, 54ST, 63P, 82A, 71L, 93L
November 2004
Mutation
RTI: 41L, 67N, 74LV, 118IV, 210W, 215Y
VL 2950/mL, CD4 127/µL
L24I
-2
M36I
2
K43T
M46L
2 5.00
1
I47V
6 4.00
I50L/V
-4
I54A/M/V
3
200
I54L
-7
150
Q58E
5
100
T74P
6 1.00
CD4
2000
1999
1998
1997
1996
1995
1994
1992
50
L76V
-2
V82L/T
5
HIV RNA
N83D
I84V
4
2
6.00
3.00
2.00
0.00
HIV RNA (cop/mL)
250
Nov-04
300
Nov-03
350
Sep-03
400
2002
450
1991
1
2001
500
CD4 (cells/µL)
L10V
ART: TVF,DDI,LPV/r,SQV,T20
NNRTI: none
0
Weight
November 2004
VL 2950/mL, CD4 127/µL
AZT, 3TC, TFV, Tipranavir/r
140
5
4
100
3
80
60
2
40
1
CD4
HIV RNA
Mar 07
Jul-06
Apr-06
Feb-06
Oct-05
Apr-05
Feb-05
0
Dec-04
20
Nov-04
CD4 (cells/µL)
120
0
HIV RNA (cop/mL)
6
160
November 2004
VL 2950/mL, CD4 127/µL
AZT, 3TC, TFV, Tipranavir/r
140
5
4
100
3
80
60
2
40
1
CD4
HIV RNA
Mar 07
Jul-06
Apr-06
Feb-06
Oct-05
Apr-05
Feb-05
0
Dec-04
20
Nov-04
CD4 (cells/µL)
120
0
HIV RNA (cop/mL)
6
160
Darunavir and fosamprenavir have similar
resistance profiles with some overlap
Darunavir IAS-USA mutations
V
V
L
I
I
11
32
33
47
I
I
F
V
I
G
L
I
L
50 54
73
76
84
89
V M
L
S
V
V
V
Overlap mutations darunavir and fosamprenavir
V
I
I
32
47
I
I
G
L
I
50 54
73
76
84
V
V M
L
S
V
V
I
I
Overlap mutations
L
V
M
10
32
46 47
F
I
R
V
I
I
L
V
I
G
L
V
I
L
50 54
73
76
82
84
90
V
S
V
A
F
S
T
V
M
L
V
M
Fosamprenavir IAS-USA mutations
Johnson VA et al. Top HIV Med 2008;16:62–68
Minor mutations
Major mutations
Darunavir and tipranavir have distinct
resistance profiles with little overlap
Tipranavir weighted score mutations1
L
L
M
K M
10
24
36
43 46 47
50 54 58
V
I
I
T
L
L
I
V
I
V
I
Q
T
L
74 76
A E
M
V
P
V
V N
I
82 83 84
L
T
D V
L
Increased response
Minor mutations
Major mutations
V
V
L
I
11
32
33
47
I
I
F
V
I
I
G
L
I
L
50 54
73
76
84
89
V
M
S
V
V
V
Darunavir IAS-USA Mutations2
L
1. Scherer J et al. 11th EACS 2007, Madrid, Spain. Poster P3.4/07
2. Johnson VA et al. Top HIV Med 2008;16:62–68
Susceptibility to tipranavir or darunavir in
patients failing PI-containing regimens
• Analysis of 1316 genotypes from PI-experienced patients
never exposed to TPV or DRV
TPV
DRV
Resistance associated with
prior failure on:
No specific
PIs identified
fAPV (p<0.001)
LPV (p=0.042)
Hypersusceptibility mutations
associated with prior failure
on:
fAPV (p<0.001)
ATV (p=0.0012)
ND
ND, not done
Resistance to TPV assessed using weighted mutation score
Resistance to DRV when ≥3 key mutations present
Garrido C et al. Antivir Ther 2008;13 (Suppl 3): A107
2006/2007 guideline paradigm shift for
treatment-experienced patients
‘Goal for all patients
is to achieve an
undetectable viral load’
‘Resistance testing
should be performed
to assist in selecting active
drugs in case
of virologic failure’
‘Use at least two,
preferably three
fully active agents’
DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, 2008; IAS-USA Panel.
Treatment for Adult HIV Infection. Recommendations of the IAS-USA Panel 2006
TPV/r + enfuvirtide (T20):
RESIST 156 weeks
40
% of patients with VL <50
copies/mL
35
TPV/r + new T20
30
CPI/r + new T20
25
21.8
20
15
10
5
0
Hicks C et al. 11th EACS 2007, Madrid, Spain. Poster P7.3/25
9.3
New drug classes: lasting response
with at least two active drugs
Week
Mean change from baseline in HIV RNA
log10 cop/mL
0
4
8
12
16
20
24
0
EVG with ≥1 active NRTI or first use of T20 (n=47)
-0.5
-1
-1.5
-2
-2.5
Zolopa A et al. 14th CROI 2007, Los Angeles, USA. Abstract 143LB
EVG = elvitegravir
New drug classes: monotherapy failed
to show a lasting response
Week
Mean change from baseline in HIV RNA
log10 cop/mL
0
4
8
12
16
20
24
0
EVG with ≥1 active NRTI or first use of T20 (n=47)
-0.5
EVG with no active drugs in OBT (n=26)
-1
-1.5
-2
-2.5
Zolopa A et al. 14th CROI 2007, Los Angeles, USA. Abstract 143LB
EVG = elvitegravir
Tipranavir + elvitegravir:
no significant PK interactions
Mathias A et al. 4th IAS 2007, Sydney, Australia. Poster TUPDB06
Tipranavir + raltegravir:
BENCHMRK studies (48 weeks)
Proportion of patients with VL <50 copies/mL
73
40
Raltegravir+TPV/r* in OBT
Placebo+TPV/r* in OBT
* TPV sensitive by genotypic testing
0
20
40
Cooper et al.; NEJM 2008; 359: 355-365
60
% patients
80
Tipranavir + raltegravir:
no clinically-relevant PK interactions
• In presence of tipranavir/r:
• C12h of raltegravir was decreased1,2
• AUC0-12h and Cmax of raltegravir were not clinically
relevantly affected1
• No overall effect on efficacy
• Comparable efficacy observed in 100 patients receiving
raltegravir plus either TPV/r or a control PI3
• Tipranavir can be co-administered with raltegravir
without dose adjustment3
1. Wenning LA et al. 46th ICAAC 2006, San Francisco, USA. Abstract A-374; 2. Rahal A et al. 9th IWCPHT 2008.
Abstract 25; 3. Raltegravir Prescribing Information, Merck and Co Inc. October 2007.
Tipranavir + maraviroc:
MOTIVATE studies (24 weeks)
Proportion of patients with VL <50 copies/mL
59.4
Maraviroc + TPV/r* in OBT (n=32)
43.8
Placebo + TPV/r* in OBT (n=16)
* TPV sensitive by genotypic testing
0
20
40
60
Patients (%)
van der Ryst E et al. 4th IAS Sydney 2007. Poster WEPEB115LB
80
Tipranavir + maraviroc:
no significant PK interactions
Mean MVC concentration
(ng/mL)
• No effect on maraviroc AUC
• No clinically significant interaction
1000
100
10
MVC + TPV/r (500/200)
MVC + placebo
1
0
2
4
6
8
Time post dose (h)
Abel S et al. 10th EACS 2005, Dublin, Ireland. Abstract LBPE4 3/15;
http://www.hiv-druginteractions.org/new/Uploaded_Attachment/52_Maraviroc%20Oct07.pdf
10
12
Tipranavir can be combined with new
drug classes without dose adjustment
Drug class
Drug name
Fusion inhibitor
Fuzeon®
enfuvirtide (T20)
CCR5 inhibitor
Celsentri®
(maraviroc)
Integrase inhibitor
Isentress™
(raltegravir)
Integrase inhibitor
Elvitegravir
(GS-9137)
Combination with
TPV/r




Vourvahis M et al. Pharmacotherapy 2007;27:888–909; Raffi F et al. 4th IAS 2007, Sydney, Australia. Poster WEPEB045;
Mathias A et al. 4th IAS 2007, Sydney, Australia. Poster TUPDB06; Wenning LA et al. 46th ICAAC 2006, San Francisco, USA. Abstract A-374;
Markowitz M et al. XVI Int AIDS Conference 2006. Abstract B20; Abel et al. 10th European AIDS Conference 2005. Abstract LBPE4.3/15
Conclusions
‘Goal for all patients
is to achieve an
undetectable viral load’
•
‘Resistance testing
be performed
•toshould
TPV/r
provides durable efficacy
assist in selecting active
drugs in case
of tolerability
virologic failure’
Overall
comparable to other
‘Use at least two,
preferably three
fully active agents’
CPIs
Conclusions
‘Goal for all patients
is to achieve an
undetectable viral load’
‘Resistance testing
•should
TPV/r
and DRV/r have distinct
be performed
to assist in selecting
active profiles
resistance
drugs in case
• of
TPV/r
weighted
mutation score:
virologic
failure’
reliable tool to better predict susceptibility
‘Use at least two,
preferably three
fully active agents’
Conclusions
‘Goal for all patients
is to achieve an
undetectable viral load’
‘Resistance testing
should be performed
• to TPV/r
new classes
can achieve
assist in +
selecting
active
and
maintain
drugs
in case undetectable VL in
of
virologic failure’
treatment-experienced
patients
‘Use at least two,
preferably three
fully active agents’
Panel
Discussion
Pedro Cahn
Sharon Walmsley
Jan van Lunzen
Panel
Discussion
Pedro Cahn
Sharon Walmsley
Jan van Lunzen