Slide 1 of XX
Antiretroviral Therapy:
A Case-Based Panel Discussion
(Part I)
Michael S. Saag, MD
Eric S. Daar, MD
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
MERGED: 03-21-13
IAS–USA
Slide 2 of 50
Case 1
– 30 yo white man
– Diagnosed on routine insurance
examination
– PMHx remarkable for HTN, diet controlled
– No medications
– Understands treatment issues and wants
to begin therapy if you think it is
appropriate
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 3 of 50
Case 1b
– 30 yo white man
– Diagnosed on admission to jail for
disorderly conduct
– PMHx remarkable for HTN, diet controlled
and paranoid schizophrenia
– Doesn’t take any medications and doesn’t
want to
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 4 of 50
Latently Infected
CD4+ Lymphocytes
HIV Infected
Cells
HIV virions
Antiretroviral Rx
Uninfected Activated
CD4+ Lymphocytes
M Saag, UAB
Uninfected Resting
CD4+ Lymphocytes
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 6 of 50
Effect on inflammation in predicting mortality higher in HIV
disease than the general population (SOCA/SCOPE)
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Hunt et al CROI 12
Slide 7 of 50
T cell “activation” is lower in treated than untreated
adults, but consistently higher than “normal”
P < 0.001
80
% CD38+HLADR+
CD8+ T Cells
P < 0.001
60
40
20
0
HIV +
HIV
Negative
Untreated
(n=82)
(n=82)
NonHIV +
Controller
ART
(n=65)
(n=65)
HAART
HIV –
(n=132)
(n=132)
Hunt et al JID 2003, PLoS ONE 2011 and unpublished
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 9 of 50
Permanent Loss of CD4 if Wait to Start
– >350
CD4 counts return
to near-normal levels
– ≤350 cells/mm3: CD4 counts
significantly increased but
plateau after 4 years below
normal range
cells/mm3:
• Differences in CD4 counts
associated with differences
in morbidity and mortality
Median CD4 Counts Over 6 Years
Stratified by Baseline CD4 Count
CD4 Count (cells/mm3)
• CD4-count increases on
sustained suppressive
(<400 c/mL) ARV treatment
(n=655) by baseline count
900
800
700
500
500
400
300
200
<200
100
201–350
>350
0
0
1
2
3
4
5
6
Years After Starting HAART
Moore RD, Keruly JC. Clin Infect Dis 2007;44:441-446.
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 11 of 50
HOPS Cohort: Resistance Development
GT mutations and virologic failure1
p=0.076
p=0.007
Any
mutation
(n=78)
NRTI mut.
among
NRTI-exp
(n=50)
p=0.051
p=0.103
50
Patients (%)
• Major mutations
50% less likely in
pts starting with
CD4+ >350 vs <200
cells/mm3, despite
greater treatment
exposure
50
40
30
20
10
0
NNRTI mut.
among
NNRTI-exp
(n=37)
0-199 cells/mm3
200-349 cells/mm3
>350 cells/mm3
1. Uy JP, et al. 4th IAS, Sydney 2007, #WEPEB017; 2. van Sighem B, et al. ibid, #WEPEB016
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
PI mut.
among
PI-exp
(n=48)
Slide 13 of 50
Most New Infections Transmitted by
Persons who Do Not Know Their Status
~25%
Unaware
of
Infection
account for…
~75%
Aware
of
Infection
Source: G. Marks et al. AIDS 2006
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
~54%
New
Infections
~46%
of New
Infections
Slide 15 of 50
Reasons to Start Early:
•
•
•
•
•
•
•
The Biology
Association of Inflammation and Disease
Better Tolerated Medications Today
Randomized Controlled Trial Data
Cohort Data
Public Health
Common Sense!
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 16 of 50
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 17 of 50
Relative Time on Treatment…
40 years on Rx
CD4 650/ul
35 years on Rx
5 years
CD4 500/ul
30
35
40
45
50
55
AGE (years)
50
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
65
70
Slide 18 of 50
Relative Time on Treatment…
40 years on Rx
HARM?
CD4 650/ul
35 years on Rx
5 years
CD4 500/ul
30
35
40
45
50
55
AGE (years)
50
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
65
70
Slide 19 of 50
So ….what is the harm?
• Destruction of Lymphoid Tissue
• Inflammation
• Increased Cardiovascular Events
• Increased incidence of certain
malignancies
• Increased ‘Aging’
• Accelerated Cognitive Decline
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 20 of 50
Conclusions
• Balance of data support starting Rx in ~
all individuals regardless of CD4+ T cell
counts
– Understanding of HIV pathogenesis
– Cohort data
– Public health implications
– No randomized clinical trial data for higher
CD4 counts (START study is enrolling)
• Waiting until RCT data could well lead to
harm that likely will not be reversible
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 21 of 50
Case 2
 42 year old man diagnosed with HIV in 1999;
several OIs
 Has ‘taken’ most existing antiretroviral drugs
available, on and off, for years
 Currently on TDF / FTC / DRV / rit
 CD4 count is 33 /µL (nadir CD4 = 6)
 CD4 count 3 months ago was 76 cells/µL
 HIV RNA 128,000 c/mL (max VL 167,000)
 Phenotype: Pan-sensitive
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 22 of 50
Case 3
34 yo woman is diagnosed with TB
As part of evaluation she is found to be HIV+
Initial lab values
— CD4 82 cells/µL
— VL 76,000 c/mL
No other significant medical condition
She is started on 4-drug anti-TB therapy
(including INH and rifabutin)
Virus is wild-type virus
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 23 of 50
Case 1
—30 yo white man
—Diagnosed on routine insurance
examination
—PMHx remarkable for HTN, diet controlled
—No medications
—Understands treatment issues and wants
to begin therapy if you think it is
appropriate
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 24 of 50
A 49 year old asymptomatic man
presents to your clinic after recently
being diagnosed with HIV
•
•
•
•
•
History of HTN with CrCl ~75 mL/min
HBsAb+, HCV antibody negative
CD4 cells repeatedly 500-700 cells/uL
Plasma HIV RNA 30-50,000 copies/mL
Not anxious to start antiretrovirals but willing
if you think it is necessary
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 25 of 50
Factors to consider in choosing
first-line therapy
•
•
•
•
•
•
•
•
Patient’s willingness to commit to therapy
Baseline resistance
Efficacy data
Tolerability
Convenience
Comorbid conditions
Consequences of failure (resistance)
Since the introduction of potent ARV therapy
preferred regimens all include NRTIs + third drug
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 26 of 50
Boosted-Protease Inhibitors
KLEAN1
(ITT-E, TLOVR)
48 weeks
100
100
80
66
65
CASTLE3
(ITT, NC=F)
96 weeks
ARTEMIS2
(ITT, TLOVR)
96 weeks
80
100
79
71
80
50
50
50
40
40
40
20
20
20
0
n=434 N=444
LPV/r
FPV/r
400/100 700/100
BID
BID
0
n=346 n=343
LPV/r DRV/r
QD or 800/100
BID
QD
0
68
74
n=443 n=440
LPV/r
ATV/r
400/100 300/100
BID
QD
Adapted from: 1. Eron J, et al. Lancet 2006; 368:476-482; 2. Mills A, et al. AIDS May 29, 2009
3. Molina J-M, et al. 48th ICAAC/46th IDSA , Washington, DC, 2008. Abst. H-1250d
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
ATV/r vs. EFV
Primary Endpoint
Daar ES, et al. Ann Intern Med 2011; 154:445-456.
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 27 of 50
Slide 28 of 50
STARTMRK: RAL vs. EFV
ITT, NC=F
Percentage of Patients with
HIV RNA Levels <50 Copies/mL
100
86
81
75
76
69
67
71
80
82
79
50
61
40
20
CD4 Change: RAL +374 vs. EFV +312
0
Weeks
0
12 24
48
72
96
280
281
281
282
281
282
120
144
168
192
216
240
Number of Contributing Patients
Raltegravir 400 mg BID
Efavirenz 500 mg QHS
281 278 279
282 282 282
250
281
280
281
281
282
281
282
Rockstroh J, et al, 19th IAC; Washington, DC; July 22-27, 2012; Abst. LBPE19.
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
250
282
279
279
Slide 29 of 50
Pooled ECHO and THRIVE: Virologic
Response (ITT-TLOVR)
84.3%
82.3%
Rimsky L, et al. 50th ICAAC 2010, Boston, MA. Abst. H-1810
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 30 of 50
Pooled ECHO and THRIVE:
Virologic Response (ITT-TLOVR)
Rimsky L, et al. 50th ICAAC 2010, Boston, MA. Abst. H-1810
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 31 of 50
GS102 & GS103: EVG/COBI/TDF/FTC vs.
EFV/TDF/FTC or ATV/RTV + TDF/FTC
Randomized, Phase III, Double-blind, Double Dummy,
Active-controlled, International Studies
GS 102
Quad QD
~89% men
33% >105 c/mL
CD4= ~385 c/uL
EFV/FTC/TDF Placebo QD
EFV/FTC/TDF QD
Treatment Naïve
Quad Placebo QD
HIV-1 RNA ≥5,000 c/mL
Any CD4 cell count
eGFR ≥70 mL/min
Quad QD
ATV/r +TDF/FTC Placebo QD
GS 103
~90% men
~41% >105 c/mL
CD4= ~370 c/uL
QUAD Placebo QD
ATV/r +TD/FTC QD
48 weeks
Sax P, et al, Lancet 2012: 379::2439-48; DeJesus E, et al, Lancet 2012; 379: 2429-38
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
192 weeks
Slide 32 of 50
Study 236-102: Primary Endpoint:
HIV-1 RNA < 50 copies/mL
+3.6%, 95% CI 3.6 (-1.6% to +8.8%)
CD4+ change: Quad +239 vs. EFV +206 c/mm3 (p=0.009)
No difference by baseline characteristics
Sax P, et al. 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 101.
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 33 of 50
Study 236-102:
Common Adverse Events
Quad
(n=348)
Treatment Emergent Adverse Events in ≥ 10% of subjects (%)
Diarrhea
23%
Nausea *
21%
Abnormal Dreams ^
15%
Upper Respiratory Infection
14%
Headache
14%
Fatigue
12%
Insomnia *
9%
EFV/FTC/TDF
(n=352)
19%
14%
27%
11%
9%
13%
14%
Depression
9%
11%
Dizziness ^
7%
24%
Rash #
6%
12%
* p<0.05; ^ p<0.001; # p=0.009
Sax P, et al, Lancet 2012: 379::2439-48
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 34 of 50
Percent with HIV RNA <50 c/mL (ITT, M=F)
Study 236-103: ATV/r vs.
TDF/FTC/COBI/EVG HIV-1 RNA < 50 c/mL
100
92%
90
88%
80
Diff: 3.5% (95% CI: -1.0 to 8.0)
70
50
QUAD
ATV/r
50
40
30
20
10
0
BL 2
4
8
12
16
24
32
40
48
Week
Changes in CD4+ count: Quad +207 vs. ATV/r +211 cells/mm3 (p=0.61)
No difference by baseline characteristics
DeJesus E, et al, Lancet 2012; 379: 2429-38
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 35 of 50
Study 236-103:
Adverse Events
Adverse Events > 10%
in Either Group
Quad
(n=353)
ATV/r + FTC/TDF
(n=355)
Diarrhea
22%
27%
Nausea
20%
19%
Upper respiratory infection
15%
16%
Headache
15%
12%
Fatigue
14%
13%
Ocular icterus
1%
14%
Discontinuation rates due to renal events were identical in
both arms (0.3%)
DeJesus E, et al, Lancet 2012; 379: 2429-38
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 36 of 50
TDF/FTC/EVG/COBI vs. EFV or
ATV/r: Lipid changes
P <0.001
P= 0.001
P =0.001
P =0.44
P =0.006
Conclusion: While some lipid fractions better with Quad than EFV or ATV/r, overall
differences were modest and unlikely to be of clinical significance.
Sax P, et al, Lancet 2012: 379::2439-48; DeJesus E, et al, Lancet 2012; 379: 2429-38
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 37 of 50
EVG/COBI/TDF/FTC vs. EFV or ATV/r:
Creatinine Changes
Conclusion: Cobicistat is associated with reduced active secretion of
creatinine in the renal tubules leading to initial rises in creatinine levels.
Sax P, et al, Lancet 2012: 379::2439-48; DeJesus E, et al, Lancet 2012; 379: 2429-38
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 38 of 50
A5202: Study Design
Arm
A
HIV-1 RNA ≥1000 c/mL
Any CD4+ count
> 16 years of age
ART-naïve
1857
N=1858
enrolled
B
Randomized
Randomized 1:1:1:1
1:1:1:1
C
Stratified by screening HIV-1 RNA
(< or ≥ 100,000 c/mL)
Enrolled 2005-2007
D
Followed through Sept 2009, 96 wks after
last pt enrolled
TDF/FTC QD
ABC/3TC Placebo QD
ABC/3TC QD
TDF/FTC Placebo QD
TDF/FTC QD
ABC/3TC Placebo QD
ABC/3TC QD
TDF/FTC Placebo QD
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
EFV
QD
EFV
QD
ATV/r
QD
ATV/r
QD
Slide 39 of 50
A5202: Time to Virologic Failure in
Patients with HIV RNA >100,000 c/mL
Probability of No Virologic Failure
Probability of No Virologic
Failure (%)
100
TDF-FTC (26 events)
80
ABC-3TC (57 events)
60
40
P<0.001, log-rank test
Hazard ratio, 2.33 (95% CI, 1.46-3.72)
20
0
0
12
24
No. at Risk
36
48
60
72
84
Weeks since Randomization
96
108
ABC-3TC
398
363
313
267
222
188
137
87
49
20
TDF-FTC
399
361
321
284
236
204
150
104
65
23
Sax PE, et al. NEJM 2009;361:2230-2240.
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
ABC/3TC vs. TDF/FTC
Low Viral Load Stratum
Sax PE, et al. JID 2011: 204:1191-1201.
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 40 of 50
Slide 41 of 50
HEAT: Virologic Failure by Baseline
HIV-1 RNA (A5202 Efficacy Endpoint)
90
87
87
90
80
60
40
20
15%
22%
4%
80%
18%
~59%
~37%
19%
50%
18%
40%
63%
20%
41%
0%
0
n=
100%
Proportion of Subjects with VF
Percent without Virologic Failure
100
<100,000
≥100,000
188
155
205
ABC/3TC
140
ABC/3TC
≥500,000 c/mL
250,000 - <500,000 c/mL
Pappa K, et al. 17th IAC, Mexico City, 2008. Abst. THAB0304.
Young B, et al. 48th ICAAC/46th IDSA, Washington, DC, 2008. Abst. H-1233.
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
TDF/FTC
100,000 - <250,000 c/mL
<100,000 c/mL
Slide 42 of 50
Relative Risk of MI (95% CI)
D:A:D Study: NRTIs and Risk of MI
1.9
1.5
1.2
1
**
0.8
Recent Exposure*: yes/no
Cumulative Exposure: per year
0.6
#PYFU:
#MI:
ZDV
138,109
523
ddI
74,407
331
ddC
29,676
148
d4T
95,320
405
3TC
152,009
554
ABC
53,300
221
TDF
39,157
139
Adjusting for eGFR does not change ABC MI finding:
Adjusted RR 1.89; 95% CI (1.46 – 2.44; P=0.0001)
* Recent use=current or within the last 6 months.
**Not shown (low number of patients currently on ddC)
Lundgren J, et al. 16th CROI, Montreal, Canada, 2009. Abst. 44LB. Sabin C, et al. Lancet
2008;371:1417-26.
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 43 of 50
Concerns regarding NRTIs
• Many studies have not seen relationship
between ABC and CV events
• TDF-associated with greater decline in bone
mineral density
• TDF-associated with variable decline in
renal function
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
DHHS Guidelines for Adolescents/Adults:
What to Start
Preferred
Regimens
• EFV/TDF/FTC
• ATV/r + TDF/FTC
• DRV/r (once daily) + TDF/FTC
• RAL + TDF/FTC
[Pregnant Women Only: LPV/r (twice daily) + ZDV/3TC]
Alternative
Regimens
• EFV + ABC/3TC
• RPV + (TDF or ABC)/(FTC or 3TC)
• ATV/r or DRV/r + ABC/3TC
• FPV/r or LPV/r (qd or bid) ABC/3TC or TDF/FTC
• RAL + ABC/3TC
• EVG/COBI/TDF/FTC (9/18/12)
Acceptable
Regimens
• EFV or RPV + ZDV/3TC
• NVP + TDF/FTC or ZDV/3TC or ABC/3TC
• ATV + (ABC or ZDV)/3TC
• ATV/r, DRV/r, LPV/r, FPV/r , RAL + ZDV/3TC
• MVC + ZDV or ABC/3TC
• SQV/r + TDF/FTC or ABC/3TC or ZDV/3TC (with caution)
Slide 44 of 50
DHHS Guidelines. Available at:
http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf . Revision March 27, 2012.
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 45 of 50
ART: What to Start
IAS–USA Recommendations, 2012
Component
Recommended Regimens
NNRTI plus nRTIs
• Efavirenz/tenofovir/emtricitabine (AIa)
• Efavirenz plus abacavir/lamivudine (AIa)
in HLA-B*5701-negative patients with baseline
plasma HIV-1 RNA <100,000 copies/mL
PI/r plus nRTIs
• Darunavir/r plus tenofovir/emtricitabine (AIa)
• Atazanavir/r plus tenofovir/emtricitabine (AIa)
• Atazanavir/r plus abacavir/lamivudine (AIa)
in patients with plasma HIV-1 RNA <100,000
copies/mL
InSTI plus nRTIs
• Raltegravir plus tenofovir/emtricitabine (AIa)
Thompson MA, et al. JAMA. 2012;308(4):387-402
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 46 of 50
Your Patient
• 43 year old man found to be HIV
infected
• HIV VL 56,000 c/ml
• CD4 count 340 cells/ul
• Seropositive for HBV
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 47 of 50
Initial Evaluation
• Physical exam: normal; no
hepatosplenomegaly
• Initial laboratory studies
– ALT 1.7 x ULN, bilirubin normal
– Platelet count: 150,000
– HCV Ab negative
– HBV DNA 6.1 x 105 IU/mL
–HBsAg+ / HBeAg+
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 48 of 50
FDA Approved Therapies
First Line Therapy
Year
Peginterferon alfa-2a
2005
Entecavir
2005
Tenofovir
2008
Second Line Therapy
Year
Adefovir dipivoxil
2002
Telbivudine
2006
Third Line Therapy
Year
Lamivudine
1998
Available at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/ Accessed 02/18/10.
CLDF HBV Advisory Board
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
TDF: Virologic Suppression at Year 6
Response
HBeAg- Patients
(Study 102)
Slide 49 of 50
HBeAg+ Patients
(Study 103)
Year 5
Year 6
Year 5
Year 6
HBV DNA < 400 copies/mL
Intent-to-treat*, % (n/N)
83
(291/350)
81
(281/345)
65
(150/248)
63
(157/251)
HBV DNA < 400 copies/mL
On treatment†, % (n/N)
99
(292/295)
99.6
(283/284)
97
(170/175)
99
(167/169)
♦ 80% of 585 patients entering the open-label phase remained on study at year 6;
73% of enrolled patients remained on study
♦ HBeAg loss/seroconversion rates of 50% and 37%, respectively, through 6 years
♦ 11% of HBeAg+ patients had confirmed HBsAg loss (8% with seroconversion)
♦ No resistance to TDF was detected through 6 years
Marcellin P, et al. AASLD 2012; Boston. #374.
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.
Slide 50 of 50
HBsAg Loss Occurred in 33% of
HBeAg+ Pts Treated With 5 Years of ETV
HBsAg Loss in HBeAg-positive Patients
33%
Months
Patients
at risk
72
70
65
54
48
41
35
28
19
8
3
• HCC developed at yearly rate of 2.5% despite good viral suppression
Conclusions:
• Long-term ETV monotherapy efficiently suppressed HBV replication in
naïve HBV patients
• High rates of HBsAg loss can also be seen with this therapy
Lampertico P, et al. 63rd AASLD; Boston, MA; November 9-13, 2012; Abst. 366.
From MS Saag, MD and ES Daar, MD at San Francisco, CA: March 29, 2013, IAS-USA.