Cco treatment simplification_downloadable

Keeping It Simple: Treatment
Simplification in HIV Management
This program is supported by an educational grant from

clinicaloptions.com/hiv
Keeping It Simple: Treatment Simplification in HIV Management
About These Slides
 Users are encouraged to use these slides in their own
noncommercial presentations, but we ask that content
and attribution not be changed. Users are asked to honor
this intent
 These slides may not be published or posted online
without permission from Clinical Care Options
(email permissions@clinicaloptions.com)
Disclaimer
The materials published on the Clinical Care Options Web site reflect the views of the authors of the
CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing
educational grants. The materials may discuss uses and dosages for therapeutic products that have not
been approved by the United States Food and Drug Administration. A qualified healthcare professional
should be consulted before using any therapeutic product discussed. Readers should verify all information
and data before treating patients or using any therapies described in these materials.

Faculty
Santiago Moreno, MD, PhD
Professor
Department of Medicine
University of Alcalá
Head
Division of Infectious Diseases
Hospital Ramón y Cajal
Madrid, Spain
Stefano Vella, MD
Director, Department of
Pharmacology and Therapeutic
Research
Research Group on HIV,
Hepatitis, Global Health
Istituto Superiore di Sanità
Rome, Italy

What Is Treatment Simplification
and Who Are Optimal
Candidates?

Definition: Treatment Simplification
 US Department of Health and Human Services[1]
– Defined broadly as a change in established effective therapy
to reduce pill burden and dosing frequency, to enhance
tolerability, or to decrease specific food and fluid
requirement[1]
 GeSIDA[2]
– A switch from a suppressive therapy regimen to a more
simple one that can maintain virological suppression[2]
1. DHHS Guidelines, October 2011. 2. GeSIDA Guidelines, January 2012.

Reasons to Consider Treatment
Simplification
 Improve adherence, convenience, and quality of life
– Reduce number of doses
– Reduce number of pills
– Reduce number of drugs
– Reduce costs
 Many physicians fear simplification out of perceived risk of
tolerability issues and loss of virologic suppression
 However, if simplification is not effective, reverting back to
the previous regimen is an option if carefully managed

Claxton AJ, et al. Clin Ther. 2001;23:1296-1310.
Adherence Inversely Related to Number of
Doses per Day
Studies of Electronic Monitoring of Adherence
MeanDose-Taking
Adherence(%)
71
0
20
40
80
100
Overall
79
QD
69
BID
65
TID
51
QID
60
P = .008
P < .001
P = .001

Stone VE, et al. J Acquir Immune Defic Syndr. 2004;36:808-816.
 HIV-positive patients on ART including ≥ 3 antiretrovirals (N = 299)
 6 US cities
 Self-report questionnaire with aid of facilitator
Not Helpful at All
Pills/Day Dosing
Frequency
Food Rules Biggest Pill
2pills5pills8pills12pills
NoneW
ith
food
Em
ptystom
ach
Extremely Helpful
QD
m
ixtim
es
QD/BID
AllQD,sam
etim
e
AllBID
Sm
allMedium
Large
0
20
40
60
80
100
Mean Relative Impact of Regimen
Features on Adherence

ARV Agents Approved for Once-Daily
Dosing and Fixed-Dose Combinations
Agents Approved for Once-Daily Dosing
Class US EU
NRTIs
ABC
3TC
ddI
FTC
TDF
ABC
3TC
ddI
FTC
TDF
NNRTIs
EFV
NVP-XR
EFV
NVP-XR
PIs
ATV/RTV
FPV/RTV (for tx-naive patients only)
DRV/RTV (for tx-naive patients or tx-exp patients
without DRV resistance mutations)
LPV/RTV (for tx-naive patients only)
ATV/RTV
DRV/RTV (for tx-naive patients or tx-exp patients
without DRV resistance mutations)
LPV/RTV (if necessary)
Approved Once-Daily Fixed-Dose Combinations
Class US EU
NRTIs
TDF/FTC
ABC/3TC
TDF/FTC
ABC/3TC
PIs LPV/RTV LPV/RTV
Two drug classes
EFV/TDF/FTC
RPV/TDF/FTC
EFV/TDF/FTC
RPV/TDF/FTC

DHHS Guidelines, October 2011.
 Patients without a history of treatment failure or drug-
resistant virus
 Patients receiving complex regimens
– However, for some forms of treatment simplification (eg,
boosted PI monotherapy), good adherence is a prerequisite
Optimal Candidates for Treatment
Simplification

 In patients with controlled viremia and no tolerability
issues, simplifying treatment to improve quality of life
should be considered[1-4]
 When switching treatment, for whatever reason,
maintenance of virologic suppression remains the main
concern
 Efficacy and likely adherence to the new regimen should
be considered
 Numerous clinical trials have studied the efficacy, safety,
and tolerability of a switch in patients with stable virologic
suppression
1. DHHS Guidelines, October 2011. 2. GeSIDA Guidelines, January 2012. 3. EACS Guidelines, 2011.
4. Thompson MA, et al. JAMA. 2010;304;321-333.
Summary and Additional Considerations

Simplification Strategies:
Within-Class Simplifications

Within-Class Simplifications
 Preserves unused drug classes for potential future use
 Types of simplifications
– PI substitutions
– Simplification from twice-daily PI to once-daily PI
– Simplification from boosted PI to unboosted PI
– NNRTI substitutions
– Simplification to agents with reduced dosing frequency or
coformulated agents
– NRTI substitutions
– Simplification to agents with reduced dosing frequency or
coformulated agents

Patient Case: Medical History
 27-yr-old white MSM
 Diagnosed HIV positive in January 2004
 Otherwise healthy; no past medical history of interest
 Blood cell count and chemistry: no significant
abnormalities
 CD4+ count: 325 cells/mm3
; HIV-1 RNA: 4.7 log10 c/mL
 Baseline HIV genotype: K103N
 HLA-B*5701: negative
 HAV, HBV immune; HCV antibody negative

Patient Case: Treatment History
 Antiretroviral therapy initiated in March 2004
– TDF (QD) + 3TC (QD) + LPV/RTV (BID)
 Medication generally well tolerated
– Loose stools twice daily
 After 2 yrs of therapy
Date HAART CD4 VL Creat,
mg/dL
HDL,
mmol/L
LDL,
mmol/L
TC,
mmol/L
TG,
mmol/L
March
2004
Naive 297 4.7 0.7 0.828 3.543 4.836 1.468
June
2006
TDF + 3TC
+ LPV/RTV
412 < 1.7 0.9 0.957 4.474 6.025 3.782

Patient Case: Considerations for
Treatment Simplification
 Suppressive regimen
 No previous failures
 Regimen well tolerated (although persistent loose stools)
 Mild to moderate rise in lipids
 BID regimen, 6 pills/day
 Patient asks if he could be switched to a regimen with
fewer pills

Rubio R, et al. HIV Med. 2010;11:545-553.
SIMPATAZ: Simplification From PI-Based
Therapy to ATV/RTV
 183 virologically suppressed patients enrolled in multicenter, prospective,
noninterventional study
– Physician recommended treatment simplification
 At Mo 12, 95% of patients on treatment maintained undetectable HIV-1 RNA
 Overall AE rate low
– 3.8% of patients experienced moderate to severe AEs, judged related to ATV/RTV
– Only 1 discontinuation judged related to ATV/RTV AE
 Total cholesterol, triglycerides, and LDL cholesterol all improved significantly
 Proportion of patients classifying themselves as highly satisfied with their
antiretroviral therapy regimen increased significantly from baseline to Month 12
after switch (47% vs 91%; P < .001)

Patient Case: Outcome
 Patient was switched to fixed-dose TDF/FTC (QD) and
to ATV 300 mg QD + RTV 100 mg QD (QD regimen,
3 pills/day)
 After 18 mos of therapy with the new regimen, loose stools
disappeared
 After more than 5 yrs on this therapy:
mg/dL
HDL,
mmol/L
LDL,
mmol/L
TC,
mmol/L
TG,
mmol/L
March
2004
Naive 297 4.7 0.7 0.828 3.543 4.836 1.468
June
2006
TDF + 3TC +
LPV/RTV
412 < 1.7 0.9 0.957 4.474 6.025 3.782
August
2011
TDF/FTC +
ATV/RTV
596 < 1.7 0.9 0.931 3.879 5.431 2.314

Gatell J, et al. Clin Infect Dis. 2007;44:1484-1492.
P = .004
P = .53
P < .001
0
5
10
15
20
25
All Patients Patients on
Boosted PI at BL
Patients on
Unboosted PI at BL
PatientsWithHIV-1RNA
≥50copies/mLatWk48(%)
ATV (n = 278) Control PI (n = 141)
7
16
8
11
5
22
 Switched patients experienced significantly fewer fasting triglyceride, total cholesterol,
and non-HDL cholesterol elevations vs control patients (P < .001)
 Comparable rates of AE-related discontinuations and serious AEs between arms
SWAN: Switching PI-Based Therapy
to ATV + NRTIs for Tx Simplification

Squires K, et al. IAS 2011. Abstract MOPE215.
ARIES: Switch From a RTV-Boosted PI to
Unboosted ATV
P = .390
0
20
40
60
80
100
ATV
HIV-1RNA<50c/mL
atWk144(%)
77 73
ATV/RTV
 515 virologically suppressed treatment-naive patients with no evidence of
virologic failure during 36-wk induction phase of ATV/RTV + ABC/3TC
randomized to switch to unboosted ATV or no change for 48 wks
Tx-Related Grade 2-4
AEs, %
ATV
(n = 189)
ATV/RTV
( n = 180)
BL to Wk 36 26 30
 Hyperbilirubinemia 13 13
 Diarrhea 4 3
 Nausea 3 2
Wk 36 to Wk 144 13 23
 Hyperbilirubinemia* 6 14
*P = .0232
 Changes in median lipid levels from
randomization to Wk 144 more favorable
with ATV vs ATV/RTV therapy

Patient Case: Final Outcome
 Patient was switched to fixed-dose ABC/3TC (QD) and to unboosted
ATV 400 mg QD (QD regimen, 3 pills/day)
– TDF decreases unboosted ATV concentrations by 20% to 40% and,
therefore, should only be coadministered with RTV-boosted ATV[1]
 After 6 mos of therapy with the new regimen:
mg/dL
HDL,
mmol/L
LDL,
mmol/L
TC,
mmol/L
TG,
mmol/L
March
2004
Naive 297 4.7 0.7 0.828 3.543 4.836 1.468
June
2006
TDF + 3TC
+ LPV/RTV
412 < 1.7 0.9 0.957 4.474 6.025 3.782
August
2011
TDF/FTC +
ATV/RTV
596 < 1.7 0.9 0.931 3.879 5.431 2.314
February
2012
ABC/3TC +
ATV
622 < 1.7 0.8 1.138 3.491 4.526 1.524
1. Atazanavir PI.

Out-of-Class Simplifications

Out-of-Class Simplifications
 Can be useful option for patients with tolerability issues
 Strategies
– Simplification from PI-based regimen to NNRTI-based regimen
– NVP-based regimens
– EFV/FTC/TDF
– RPV/FTC/TDF
– No data but ongoing clinical trial[1]
– Simplification from PI-based regimen to RAL
– Simplification from RAL + FTC/TDF to EVG/COBI/FTC/TDF
– No data but ongoing clinical trial[2]
1. ClinicalTrials.gov. NCT01252940. 2. ClinicalTrials.gov. NCT01533259.

 33-yr-old white man
 Injection drug user until 1995 when he initiated a
methadone-maintenance program
 Known HIV positive in 1994 when he presented with
pulmonary tuberculosis
– At that time, CD4+ cell count: 390 cells/mm3
, HIV-1 RNA: 4.4
log10 copies/mL
 Lost to follow-up; never attended clinic appointments

 Seen at the clinic in January 2003
 Receiving methadone but no other medications
 No complications after TB (treatment was completed in a DOT
program)
 At this time
– CD4+ cell count: 215 cells/mm3
; HIV-1 RNA: 4.9 log10 copies/mL
– LFT results: AST 102 IU/L, ALT 97 IU/L; no other significant
findings
– Hepatitis B immune, hepatitis C antibody positive
– HIV resistance test: wild type

 ART initiated in February 2003: ABC (BID) + 3TC (BID) +
FPV/RTV (BID)
 Medication well tolerated
 The patient remained on same therapy until current
presentation
– HIV-1 RNA persistently < 1.7 log10 IU/mL
– CD4+ cell count rose to 541 cells/mm3
– Significant elevation in triglycerides (from 0.926 to 4.968
mmol/L)
– LFT similar (refused treatment for chronic hepatitis C at this
time)

 Regimen well tolerated
 Moderate increase in lipids
 BID regimen, 8 pills/day
 . . . but the patient feels well

DeJesus E, et al. J Acquir Immune Defic Syndr. 2009;51:163-174.
Simplification of PI- or NNRTI-Based
Regimens to EFV/FTC/TDF
 Patients with HIV-1 RNA < 200 copies/mL for ≥ 3 mos
randomized 2:1 to EFV/FTC/TDF or no change
– 87% vs 85% of patients who switched or maintained current
regimen maintained HIV-1 RNA < 50 copies/mL at Wk 48
– Higher rate of discontinuation for AEs in switch vs no change
arm: 5% vs 1%
– Mainly due to increase in CNS AEs
– Self-reported adherence high at baseline and during study
(≥ 96%)
– Patients randomized to EFV/FTC/TDF preferred switch at all
postbaseline study visits (P < .001)

 Patient switched to EFV/FTC/TDF (1 pill/day) and regimen was
well tolerated
 Drug-drug interaction with methadone needed minor
adjustments of methadone dose
 Patient feels his quality of life has really improved
 Latest evaluations
– HIV-1 RNA: < 1.7 log10 IU/mL
– Triglycerides lower, but still high (3.274 mmol/L)
– LFT similar (transient elastography shows only mild fibrosis [F1])

Case Discussion
 Which other out-of-class regimens may have been
appropriate for this patient?
– RPV/FTC/TDF?
– Nevirapine-based regimen?
– Raltegravir-based regimen?

1. Ena J, et al. HIV Med. 2008;9:747-756. 2. EMEA Nevirapine PI.
Simplification From Suppressive PI-Based
Therapy to NVP-Based Regimens
 Meta-analysis of 6 randomized clinical trials (N = 550) switching suppressive PI-based
therapy to NVP-based therapy or no change[1]
 Overall discontinuation rate due to AEs similar among arms
– However, NVP-based regimens led to more discontinuations because of liver toxicity compared
with PI-based therapies (7.4% vs 0%)
 Although treatment-naive women and men with CD4+ counts > 250 cells/mm3
and
> 400 cells/mm3
, respectively, should not initiate NVP, EMEA endorses switching
patients with suppressed HIV-1 RNA to NVP regardless of CD4+ count[2]
-0.5 -0.25 0 0.25 0.5
Favors PI-based therapy Favors NVP-based therapy
Study Risk Difference
(Fixed), 95% CI
Ruiz
Total (95% CI)
Arranz
Negredo
Negredo
Calza
Barreiro

SPIRAL: Switch to RAL Noninferior to
Maintaining PI/RTV Regimens
0
20
40
60
80
100
Switch to
RAL
Continue
PI/RTV
86.689.2
Free of Treatment Failure at Wk 48
(ITT, S = F)
Patients With VF RAL
(n = 4)
PI/RTV
(n = 6)
Previous VF 1 3
Previous suboptimal ART 2 3
Resistance test at VF 1 4
 Mutations 0 3 (PR, RT)
Martinez E, et al. AIDS. 2010;24:1697-1707.
Mean Change
From Baseline
to Wk 48, %
Switch
to RAL
Continue
PI/RTV
P Value
TG -22.1 +4.7 < .0001
TC -11.2 +1.8 < .0001
LDL-C -6.5 +3.0 < .001
HDL-C -3.2 +5.8 < .0001
Total to HDL-C
ratio
-4.9 -1.3 < .05

Eron J, et al. Lancet. 2010;375:396-407.
SWITCHMRK-1 and -2: Switch From Stable
LPV/RTV to RAL-Based HAART
 Predefined criteria for noninferiority: lower limit of the 95% CI for
treatment difference > -12%
RAL + ARVs, n
174 166 169 173 172 176 176 176 176 175
LPV/RTV + ARVs, n
174 171 171 171 174 178 178 177 177 178
50
60
70
80
90
100
0 4
Wks
HIV-1RNA<50c/mL(%)
8 12 24
87%
81%
∆: -6.6 (95% CI: -14.4 to 1.2)
Protocol 032 Protocol 033
50
60
70
80
90
100
0 4
Wks
8 12 24
∆: -5.8 (95% CI: -12.2 to 0.2)
94%
88%
HIV-1RNA<50c/mL(%)

Eron J, et al. Lancet. 2010;375:396-407.
SWITCHMRK -1 and -2: Significant
Decrease in Lipids With Switch to RAL
MeanChangeFromBaseline
atWk12(%)
-50
-40
-30
-20
-10
0
10
20 RAL + ARVs
LPV/RTV + ARVs
Protocol 032 Protocol 033
*
NS nps-12.8
0.7
-15.2
2.3
-41.5
3.6
-2.4
2.1
-0.9
0.8
NS nps-12.4
1.3 2.9
8.2
4.0
0.6
-0.6-2.5
-14.8
-42.8
Fasting
Cholesterol
Fasting
Non-
HDL-C
Fasting
TG†
Fasting
LDL-C
Fasting
HDL-C
Fasting
Cholesterol
Fasting
Non-
HDL-C
Fasting
TG†
Fasting
LDL-C
Fasting
HDL-C
*P < .0001; †
median change from BL at Wk 12, %.
*
*
* *
*

Reducing the Number of
Active Drugs in a Regimen

Switches That Reduce the Number of
Active Drugs in a Regimen
 Reduces drug exposure and may improve tolerability of
regimen
 Strategies
– Boosted PI monotherapy
– Avoids NRTI toxicities; reduces costs
– Ongoing clinical trials of switches to boosted PI + 3TC only
– Simplification from 2 NRTIs plus a third agent to ATV/RTV +
3TC as maintenance therapy (SALT)[1]
– Simplification from LPV/RTV plus 2 NRTIs to LPV/RTV + 3TC[2]
1. ClinicalTrials.gov. NCT01307488. 2. ClinicalTrials.gov. NCT01471821.

 39-yr-old white woman
 Known HIV positive in September 2008 (infected
presumably by unprotected heterosexual contact)
 Asymptomatic
 Past medical history: nothing significant
 CD4+ count: 220 cells/mm3
; HIV-1 RNA: 5.2 log10 c/mL
 Baseline HIV genotype: wild type
 HLA-B*5701 positive

 Antiretroviral therapy initiated in December 2008:
EFV/FTC/TDF
 Transient dizziness and abnormal dreams that resolved
spontaneously
 After 1 yr of therapy:
Date HAART CD4+ VL Creat,
mg/dL
eGFR,
mL/min/1.73 m2
December
2008
Naive 220 5.2 0.7 97
January
2010
EFV/FTC/TDF 526 < 1.7 1.5 57

 Regimen well tolerated
 Impairment of renal function
 QD, 1 pill

 Patient was switched to DRV/RTV monotherapy
 Regimen has been very well tolerated
 After 2 yrs of monotherapy:
– HIV-1 RNA remains < 1.7 log10 copies/mL
– Improvement in renal function—serum creatinine: 0.9 mg/dL;
eGFR: 89 mL/min/1.73 m2

Study MONET[1]
MONOI[2]
Design  Simplification monotherapy
 DRV/RTV 800/100 QD (n = 127)
 Wk 48 primary endpoint; 144-wk follow-up
 Simplification monotherapy
 DRV/RTV 600/100 mg BID (n = 112)
 Wk 48 primary endpoint; 96-wk follow-up
Patient population  256 experienced patients
 HAART with 2 NRTIs + either NNRTI or PI
at screening
 No previous use of DRV
 VL < 50 for ≥ 6 mos
 No hx VF
 225 experienced patients
 DRV-naive HIV-infected patients on HAART
 VL < 400 for ≥ 18 mos
 VL < 50 at screening
 No PI failure
 CD4+ nadir > 50
 All patients suppressed on DRV/RTV
600/100 mg BID + 2 NRTIs prior to
comparative study
Comparator DRV/RTV 800/100 mg QD + 2 NRTIs (n = 129) DRV/RTV 600/100 mg BID + 2 NRTIs (n = 113)
Primary endpoint  2 consecutive HIV RNA > 50 copies/mL
 Discontinuation of randomized tx (TLOVR)
• Stopping DRV/RTV or starting NRTIs in
mono arm
• Stopping NRTIs in the control arm
(switches in NRTIs permitted)
 Proportion with tx success at Wk 48
 Tx failure:
• 2 x VL > 400 within 2 wks
• Tx modification
• Withdrawal
1. Arribas J, et al. AIDS. 2010;24:223-230. 2. Katlama C, et al. AIDS. 2010;24:2365-2374.
Studies of DRV/RTV Monotherapy Switch

DRV/RTV Monotherapy: Efficacy at Last
Report
93.4 91.9
Switch (Intensification With NRTIs) Allowed
DRV/RTV
Mono
80.6
MONET 96 Wks[1]
DRV/RTV
Mono
DRV/RTV +
2 NRTIs
TLOVR, S = F
74.8 ∆ = -5.8%
(-16.0%
to +4.4%)
129127
DRV/RTV +
2 NRTIs
∆ = +1.6%
(-5.0% to +8.1%)
129127
1. Clumeck N, et al. J Antimicrob Chemother. 2011;66:1878-1885. 2. Katlama C, et al. AIDS. 2010;24:2365-2374.
Mono not noninferior
Mono noninferior
100
80
60
40
20
0
100
80
60
40
20
0
MONOI 48 Wks[2]
94.1
99.0
Lower
limit of
90% CI:
-9.1
PP Analysis
DRV/RTV
Mono
DRV/RTV +
2 NRTIs
Mono noninferior
102102
100
80
60
40
20
0
87.5 92.0
ITT Analysis
Lower
limit of
90% CI:
-11.2
DRV/RTV
Mono
DRV/RTV +
2 NRTIs
Mono not
noninferior112 113
100
80
60
40
20
0
PatientsMeeting
PrimaryEndpoint(%)
PatientsMeeting
PrimaryEndpoint(%)

DRV Monotherapy: Resistance
 MONET[1]
– Only 1 patient per arm had any evidence of genotypic resistance
– Both patients regained suppression without change in treatment
 MONOI[2]
– Virologic failure in 3 patients on monotherapy vs 0 on standard
therapy
– 1 patient had DRV resistance associated mutation that was also found
in prestudy sample; no DRV resistance associated mutations in other 2
– All 3 patients regained HIV-1 RNA < 50 copies/mL on
reintroduction of 2 NRTIs
1. Clumeck N, et al. J Antimicrob Chemother. 2011;66:1878-1885.
2. Katlama C, et al. AIDS. 2010;24:2365-2374.

Case Discussion
 Could other boosted PIs have been considered for this
patient as monotherapy?
– LPV/RTV
– ATV/RTV

Bierman WF, et al. AIDS. 2009;23:279-291.
Systematic Review of LPV/RTV
Monotherapy
Therapy Failure, Intent to Treat
Odds Ratio (95% CI)
4.71 (0.48-46.2)
1.70 (0.46-6.21)
2.17 (0.49-9.64)
1.03 (0.53-2.01)
1.67 (0.85-3.31)
1.48 (0.68-3.22)
Favors HAART
1.48 (1.02-2.13)
Studies
OK04 2005
Singh et al, 2007
KALMO
OK04 2008
MO3-613
MONARK
Overall
Favors
monotherapy
0.1 1 10 100
Odds Ratio

Study ATARITMO[1]
ACTG 5201[2]
Karlström[3]
OREY[4]
Design  Simplified
maintenance
monotherapy
 24-wk pilot study
 Simplified
maintenance
monotherapy
 24-wk pilot-study,
48-wk data
presented
 Simplification
monotherapy
 Pilot trial planned
for 72 wks
 Simplification
monotherapy
 48-wk primary
endpoint; continued
through Wk 96
Patient
population
 30 experienced pts
 HAART ≥ 6 mos or
 Switching from
IDV/RTV mono
trial
 VL < 50
 VL < 50 for ≥ 48 wks
on 2 NRTIs + PI
 CD4+ count > 250
 Pts switched to 2
NRTIs + ATV/RTV
→ ATV/RTV mono
after 6 wks
 VL < 20 for ≥ 1 yr
on HAART
 No PI experience
 VL < 50 for ≥ 6 mos
 No hx of VF
 NRTIs + ATV/RTV
≥ 8 wks → ATV/RTV
Comparator  Noncomparative  Noncomparative  Noncomparative  Noncomparative
Primary
endpoint
 2 x VL > 400 or
 3 x VL > 200 or
 4 x VL > 100
 Risk of virologic
failure (2 x VL > 200)
at 24 wks
 Number of pts w/o
VF at 72 wks
 VF: 2 x VL > 20
 To be terminated if
5 cases of virologic
failure occurred
 VL > 400 at Wk 48
 Tx discontinuation
1. Vernazza P, et al. AIDS. 2007;21:1309-1315. 2. Wilkin T, et al. J Infect Dis. 2009;199:866-871.
3. Karlström O, et al. J Acquir Immune Defic Syndr. 2007;44:417-422. 4. Pulido F, et al. EACS 2009. Abstract PS4/6.
Studies of ATV/RTV Monotherapy

Studies of ATV/RTV Monotherapy
Study ATARITMO[1]
ACTG 5201[2]
Karlström[3]
OREY[4]
Results  2 pts (7%) with
VF at Wk 24
(1 d/c, 1
protocol
violation)
 5 pts with
virologic “blips”
 34 simplified
to ATV/RTV
monotherapy
 88% (30) did not
experience VF
at Wk 48 after
simplification
 1 pt with VL =
508 at final visit
 Stopped at 15 pts
 5 VFs
 No pts
completing
72 wks on
monotherapy
without VF
 9/14 (64%) with
virologic success
after median
36 wks
 21% with tx failure
 12% with virologic
rebound
Resistance  Not tested in
plasma
samples
 5 pts genotyped
 No major PI
RAMs
 No low frequency
ATV resistance
variants detected
 3 pts genotyped
 No PI resistance
mutations
 7 pts genotyped
 1 pt with ATV
resistance
mutation N88S
at Wk 48
 1 additional pt
with N88S +
M46L after Wk 48
1. Vernazza P, et al. AIDS. 2007;21:1309-1315. 2. Wilkin T, et al. J Infect Dis. 2009;199:866-871.
3. Karlström O, et al. J Acquir Immune Defic Syndr. 2007;44:417-422. 4. Pulido F, et al. EACS 2009. Abstract PS4/6.

EACS 2011[1]
IAS-USA 2010[2]
DHHS 2011[3]
PI/RTV monotherapy
with BID LPV/RTV or
QD DRV/RTV might
represent an option in
patients with intolerance
to NRTI or for treatment
simplification
Therefore, PI/RTV
monotherapy is not
recommended except in
exceptional
circumstances when
other drugs cannot be
considered for reasons of
toxicity/tolerability
In aggregate, boosted PI
monotherapy as initial or as
simplification treatment has
been somewhat less
effective in achieving
complete virologic
suppression and avoiding
resistance. Therefore, this
strategy cannot be
recommended outside of
a clinical trial
1. EACS Guidelines version 6, 2011. 2. Thompson MA, et al. JAMA. 2010;304;321-333.
3. DHHS Guidelines, 2011.
Guidelines Differ Regarding PI
Monotherapy

Reasons to Consider Treatment
Simplification
 Improve adherence, convenience, and quality of life: active
simplification
– Reduce number of doses
– Reduce number of pills
– Reduce number of drugs
– Reduce costs
 In patients with controlled viremia and no tolerability issues,
simplifying treatment to improve quality of life should be considered
 Many physicians fear simplification out of perceived risk of tolerability
issues and loss of virologic suppression
 However, if simplification is not effective, reverting back to the
previous regimen is an option if carefully managed

Potential Benefits of Treatment
Simplification
 Several highly convenient regimens available, including newer
agents and reformulations/coformulations of older drugs with
less frequent dosing and less toxicity
– Regimens with lower pill burdens and less frequent daily dosing
are associated with better adherence
 When switching treatment, for whatever reason, maintenance of
virologic suppression remains the main concern
– Studies have identified simplification strategies that usually
maintain virologic suppression and often reduce adverse events
– Previous use of suboptimal therapy may reduce likelihood of effective
treatment response

Recommendations for Treatment
Simplification
 A boosted PI may be switched for simplification to
unboosted ATV, an NNRTI, or RAL only if full activity of
the 2 NRTIs remaining in the regimen can be guaranteed
 Complex multidrug regimens should be changed to
simpler, well-tolerated, active regimens
 BID NRTIs can be switched to QD NRTIs
 Intraclass switches preferred for drug-specific AE
 Boosted PI monotherapy may represent an option for
treatment simplification in suppressed patients without
history of failure on previous PI-based therapy
EACS guidelines version 6, 2011.

Go Online for More
Educational Programming on HIV
Treatment Simplification!
Downloadable slideset for personal study or use in your own
noncommercial talks
clinicaloptions.com/simple

Cco treatment simplification_downloadable

Empfohlen

Empfohlen

Weitere ähnliche Inhalte

Was ist angesagt?

Was ist angesagt? (20)

Andere mochten auch

Andere mochten auch (12)

Ähnlich wie Cco treatment simplification_downloadable

Ähnlich wie Cco treatment simplification_downloadable (20)

Mehr von Carlos Alberto Trapani

Mehr von Carlos Alberto Trapani (20)

Kürzlich hochgeladen

Kürzlich hochgeladen (20)

Cco treatment simplification_downloadable

Hinweis der Redaktion