adherence in tlc+: the sticky wicket michael s. saag, md center for aids research university of...
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Adherence in TLC+: The Sticky Wicket
Michael S. Saag, MD
Center for AIDS Research
University of Alabama at Birmingham
USA
One Man’s Journey to Adherence:
Michael S. Saag, MD
Center for AIDS Research
University of Alabama at Birmingham
USA
Lessons from a Career Path in HIV Research
Disclosures Grant Support / Consulting
• Ardea• Avexa• Boehringer-Ingelheim• Bristol-Myers Squibb• Gilead Sciences• GlaxoSmithKline
/ViiV• Merck
• Pain Therapeutics• Pfizer / ViiV • Progenics• Tibotec / Virco• Tobria
Translational Research
M Saag, UAB
Piatak, et al, Science, 1993
Viral Load
101
102
103
104
105
106
0 2 4 6 8 10 12
Weeks
T1/2 = 1.1 days
HIV Infected Cells
Uninfected Resting CD4+ Lymphocytes
Uninfected Activated CD4+ Lymphocytes
Antiretroviral Rx
Latently Infected
CD4+ Lymphocytes
HIV virions
M Saag, UAB
Viral Load
101
102
103
104
105
106
0 2 4 6 8 10 12
Weeks
T1/2 = 1.1 days
RNA+ cells in Lymph node vs RNA in Plasma
HIV RNA+ cells/106 LN cells0.1 1 10 100 1000 10000
Plasma Viral Load (copies/ml)
10
100
1000
10000
100000
1000000
10000000
<50
At steady state, when an actively producing cell dies, it is replaced by how
many newly infected cells?
1. One
2. Twenty – Five
3. One Hundred
4. One Thousand
5. It depends on the viral load
M Saag, UAB
VL = 100,000
VL < 50
Viral Load
101
102
103
104
105
106
0 2 4 6 8 10 12
Weeks
T1/2 = 1.1 days
Clinical Trials
Slide #24
How Did We Get Here?How Did We Get Here?How Did We Get Here?How Did We Get Here?
Sequential exposure to effective “monotherapy” in a population of largely adherent, aggressively treated patients created a cohort of individuals with highly-resistant HIV
1996 1997 1998 19992000
ZDV NVP 3TC EFV LPV
ddI SQV RTV ABC TDF
d4T IDV NFV
Slide #25
New HAART EraNew HAART EraNew HAART EraNew HAART Era
After years of sequential “monotherapy” many patients with MDR are now entering a period where more than one new medication may be readily available
2004 2005 2006 2007 2008 2009
T20 TPV DRV Maraviroc, Raltegravir Etravirine
Slide #26
10090% RESPONSE
0 60 70
8010
20
30
40
50 Bartlett, JA, et al
Abst # 586 CROI 2005
Outcomes Research
MEDICAL INFORMATICS
The FUTURE:
8 Year Survival in HAART Era8 Year Survival in HAART Era
Updated from Chen, et al, 8th CROI, 2001
CD4 Count at HAART InitiationCD4 Count at HAART Initiation
Median Median CD4CD4
% CD4 % CD4 < 200< 200
19961996 115 62.8%
19971997 180 53.8%
19981998 221 47.8%
19991999 212 49.3%
20002000 197 50.1%
20012001 277 39.5%
20022002 210 48.8%
20032003 220 47.2%
20042004 207 49.1%
Median Median CD4CD4
% CD4 % CD4 < 200< 200
20052005 278 39.6%
20062006 300 35.4%
20072007 296 35.2%
20082008 310 29.4%
Most New Infections Transmitted by Persons who Do Not Know Their Status
~25% Unaware
of Infection
~75% Aware
of Infection
account for…
~54% New
Infections
~46% of New
Infections
Source: G. Marks et al. AIDS 2006
TNT: Based on the association of viral load and HIV transmission risk
0
5
10
15
20
25
30
Viral load (HIV-1 RNA copies/ml) and HIV transmission
Tra
nsm
issi
on
rat
e p
er 1
00 P
erso
n-Y
ears
<40
0
400
-349
9
350
0-99
99
10 0
00-4
9 99
9
>50
000
Quinn TC, et al. NEJM 2000; also Fideli U, et al. AIDS Res Hum Retrovir 2001
<40
0
400
-349
9
350
0-99
99
10 0
00-4
9 99
9
>50
000
<40
0
400
-349
9
350
0-99
99
10 0
00-4
9 99
9
>50
000
All subjectsMale-to-FemaleTransmission
Female-to-MaleTransmission
Lancet 2009; 373:48-57
2009 WHO model
Slide #36
Test and TreatTest and Treat
21% of HIV-infected individuals in the U.S.
are undiagnosedRole in reducing
HIV transmissionCampsmith M et al. MMWR 2008;57:1073-76, Gardner et al. AIDS 2005;19:423-431, Marks et al. AIDS
2006;20: 1447-50, Fleming et al. 9th CROI 2002, abstract 11, Metsch et al. Clin Infect Dis 2008;47:577-584, Cohen at al. Ann Intern Med 2007;146:591-601, Diffenbach & Fauci. JAMA 2009;301:2380-82
……don’t forget don’t forget EngagementEngagement
Slide #37
Test and TreatTest and Treat
24-44% fail to enter care w/in 6
mos.
33% with known HIV NOT in regular care
21% of HIV-infected individuals in the U.S.
are undiagnosedRole in reducing
HIV transmissionCampsmith M et al. MMWR 2008;57:1073-76, Gardner et al. AIDS 2005;19:423-431, Marks et al. AIDS
2006;20: 1447-50, Fleming et al. 9th CROI 2002, abstract 11, Metsch et al. Clin Infect Dis 2008;47:577-584, Cohen at al. Ann Intern Med 2007;146:591-601, Diffenbach & Fauci. JAMA 2009;301:2380-82
……don’t forget don’t forget EngagementEngagement
Slide #38
Celebrate
Make a plan
Identify a Need
Name It
Empower Others
Join You
to
Emerge
ChallengesNew
Client-OrientedNew PatientNavigation
toEncourageConnection
toTreatment
Project CONNECTProject CONNECT
Slide #39
CONNECT: Program EvaluationCONNECT: Program Evaluation
Time Period “No Show”
Unadjusted OR (95%CI)
Adjusted OR (95%CI)a
Pre-CONNECT (n=522)
Post-CONNECT (n=361)
30.7%
17.7%
1.0
0.48 (0.35-0.68)
1.0
0.54 (0.38-0.76)
a Multivariable model controls for age, race, sex, insurance, location of residence and time from call to scheduled visit.
Wylie et al. 4th International Conference on HIV Treatment Adherence 2009
Slide #40
Mugavero, Davila, Nevin & Giordano; 4th International Conference on HIV Treatment Adherence 2009
Missed Visits
Appt. Adherence
Visit Constancy
Gap in Care
HRSA HAB Measure
Patient A Yes; 1 80% 100% No Yes
Patient B Yes; 4 33% 50% Yes Yes
Patient C No; 0 100% 75% No Yes
Patient D Yes; 1 67% 25% Yes No
Slide #41
Missed Visits and MortalityMissed Visits and Mortality
Characteristic HR (95%CI)a
Missed visit in 1st year 2.90 (1.28- 6.56)
Age (HR per 10 years) 1.58 (1.12-2.22)
CD4 count <200 cells/mm3
2.70 (1.00-7.30)
Log10 plasma HIV RNA 1.02 (0.75-1.39)
ART started in 1st year 0.64 (0.25-1.62)
a Cox proportional hazards (PH) analysis also adjusts for sex, insurance, race/ethnicity, depression, anxiety, alcohol abuse, and substance abuse.
Mugavero et al. Clin Infect Dis 2009;48:248-56
Slide #42
Retention in Care: Challenge to Retention in Care: Challenge to SurvivalSurvival
Giordano et al. Clin Infect Dis 2007;44:1493-1499
Quarters w/ visit (Visit Constancy)
N (%) of Sample
Adjusted HR (95%CI) for Mortality
4 1685 (64%) 1.0 (Referent)
3 479 (18%) 1.41 (1.10-1.82)
2 286 (11%) 1.68 (1.24-2.26)
1 169 (7%) 1.94 (1.36-2.76)
Slide #43
Expanding the Spectrum of Expanding the Spectrum of AdherenceAdherence
0
10
20
30
40
<50 50-59 60-69 70-79 80-89 90-99 100
Appointment Adherence (%)
% o
f S
am
ple
Mugavero. Top HIV Med 2008;16:156-61.
Slide #44
Expanding the Spectrum of Expanding the Spectrum of AdherenceAdherence
0
20
40
60
80
100
<50 50-59 60-69 70-79 80-89 90-99 100
Appointment Adherence (%)
% w
ith V
L<50c/m
L
Mugavero. Top HIV Med 2008;16:156-61.
Slide #45
Expanded spectrum of HIV adherence
Engagement in care includes distinct steps: Linkage, Retention and Re-engagement
Engagement in care vital for HIV treatment success at individual & population level
Early missed visits may identify patients at risk for poor long-term health outcomes
Engagement worse in groups bearing a disproportionate burden of US HIV epidemic
SummarySummary
Slide #46
Incorporate adherence to care counseling into patient encounters as a matter of routine
Evaluate “no show” phenomenon at the clinic level & revise new patient orientation
Develop partnerships with local HIV testing, clinical & supportive service providers Integrate HIV testing and linkage activities Coordinate activities around retention and
re-engagement for shared patients
What Can We Do?What Can We Do?
Slide #47
ThanksThanks
UAB 1917 Clinic Cohort supported by UAB CFAR (P30AI27767), CNICS (R24AI067039), and the Mary Fisher CARE Fund; MJM supported by NIMH (K23MH082641) & CDC
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