adherence to hiv treatment and prevention
TRANSCRIPT
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Adherence to HIV Treatment and
Prevention
David Bangsberg, MD, MPH
Director Massachusetts General Hospital Center for Global Health
Professor
Harvard Medical School
Professor, Harvard School of Public Health
Visiting Professor Mbarara University of Science and Technology
September, 2014
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Antiretroviral therapy in Africa
Warren Stevens, Steve Kaye, Tumani Corrah BMJ 2004;328:280-282
[In sub-Saharan Africa]….the potential short
term gains from reducing individual morbidity
and mortality may be far outweighed by the
potential for the long term spread of drug
resistance…. In Africa, a higher proportion of
patients are likely to fall into the category of
potential poor adherers unless resource
intensive adherence programmes are
available.
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A Social Model of Adherence for sub-Saharan Africa Ware et al PLoS Medicine 2009
Improving Health
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Resource
Scarcity
Resource
Scarcity
Improving Health
A Social Model of Adherence for sub-Saharan Africa Ware et al PLoS Medicine 2009
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Resource
Scarcity
Resource
Scarcity
Adherence
fulfills
responsibility to
helpers and
preserve
relationships
as a resource
Relationships
as resources to
overcome
economic
obstacles to
adherence
Social
Capital
Improving Health
A Social Model of Adherence for sub-Saharan Africa Ware et al PLoS Medicine 2009
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Resource
Scarcity
Resource
Scarcity
Adherence
fulfills
responsibility to
helpers and
preserve
relationships
as a resource
Relationships
as resources to
overcome
economic
obstacles to
adherence
Social
Capital
Improving Health
A Social Model of Adherence for sub-Saharan Africa Ware et al PLoS Medicine 2009
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Resource
Scarcity
Resource
Scarcity
Adherence
fulfills
responsibility to
helpers and
preserve
relationships
as a resource
Relationships
as resources to
overcome
economic
obstacles to
adherence
Social
Capital
Improving Health
A Social Model of Adherence for sub-Saharan Africa Ware et al PLoS Medicine 2009
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Stigma, Social Capital, Structural Barriers, and
Adherence in Resource-Limited Settings Bangsberg and Deeks Ann Int Med 2010
Stigma Social
Capital
Treatment
Adherence
Structural &
economic barriers
Routine Barriers
Medication side effects
Depression
Substance use
Memory
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Frequency and Duration of Treatment
Interruptions >48hrs over 24 weeks Oyugi et al AIDS 2007
Interruptions > 48 hours 199 interruptions 62 people (64%)
Mean # interruptions/person 2.0 ±2.9 (S.D) Mean duration (days) for those who have interruptions
11.5 ±9.2 (S.D)
Interruptions account for 90% of all missed doses
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Adju
sted
Odds
Rat
ios
13
**
*
Interruptions Independently Predict Virologic Failure Adjusted odds ratios of detectable HIV-RNA by categories of total non-
covered days and longest interruption 28 days prior to HIV RNA Genberg et al AIDS 2012
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Duration of MEMS Defined Treatment Interruption and
Probability of NNRTI Virologic Failure Parienti et al PLoS One 2008
n=72
Longer interval of treatment discontinuation in days
Estim
ate
d p
rob
ab
ility
of vira
l co
ntr
ol
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Real-time Adherence Monitoring Haberer et al AIDS and Behavior 2010
Wisepill Adherence Monitor
www.wisepill.com
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Real-time Adherence Monitoring Haberer et al AIDS and Behavior 2010
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Real-time Adherence Monitoring Haberer et al AIDS and Behavior 2010
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30% Laboratory Monitoring Savings
Machine “Super” Learner Targeted RNA Testing Petersen et al CROI 2013
0.80 0.85 0.90 0.95 1.00
0.1
0.2
0.3
0.4
0.5
0.6
Sensitivity
Ave
rage C
apaci
ty S
avin
gs
HIV RNA/Adherence/Clinical
Baseline HIV RNA/Adherence/Clinical
Adherence/Clinical
Clinical
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WHO TREATMENT GUIDELINES
The 2013 Guidelines
Development Group
recommends that national
HIV programmes provide
ART to all people with a
confirmed HIV diagnosis
with a CD4 count of 500
cells/mm3 or less.
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Early Treatment (CD4>250) is Associated with
More Frequent Treatment Interruptions and
Incomplete Virologic Suppression Adakun et al JAIDS 2013
• Average MEMS adherence <90%: OR=1.54 p=0.19
• Any MEMS >72 hr interruptions OR=2.21 p=0.05
• HIV RNA >400 OR=2.52 p=0.04 • Controlling for: age, sex, marital status, education,
employment, socioeconomic status, clinic travel time, Hopkins Depression score, and AUDIT-C alcohol screen, and ARV regimen
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Stigma, Social Capital, Structural Barriers, and
Adherence in Resource-Limited Settings Bangsberg and Deeks Ann Int Med 2010
Stigma Social
Capital
Treatment
Adherence
Structural &
economic
barriers
Routine Barriers
Medication side effects
Depression
Substance use
Memory
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Stigma, Social Capital, Structural Barriers, and
Adherence in Resource-Limited Settings Bangsberg and Deeks Ann Int Med 2010
Stigma Social
Capital
Treatment
Adherence
Structural &
economic
barriers
Routine Barriers
Medication side effects
Depression
Substance use
Memory
Decline in
health
and economic
status
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HIV Infected
HIV Diagnosed
Staged
ART eligible ART Initiation Retention
on ART
ART ineligible
ART eligibility
The Leaky Cascade of HIV/AIDS Care Programs in Resource Limited Settings
40%
59%
46%
68%
70%
Rosen, PLoS Med 2011; Gardner CID 2011Fox, TMIH 2010; Giordano
AIDS Care 2005; Giordano Current HIV/AIDS Reports 2005
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TREATMENT Refusal
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Pre-exposure Prophylaxis: ART in HIV
negatives to Prevent HIV Acquisition
Study Population N Results
iPrEx MSM 2499 44% efficacy
TDF2 Study Young men
and women 1200 62% efficacy
Partners PrEP
Study
Heterosexu
al couples 4758
67% efficacy TDF
75% efficacy FTC/TDF
FEM-PrEP Women 2021 No efficacy
VOICE Women 3021
(oral arms) No efficacy
Bangkok Tenofovir Study IDUs 2400 62% efficacy FTC/TDF
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Adherence and Efficacy in PrEP Trials
% of blood
samples with
tenofovir
detected
HIV protection
efficacy in
randomized
comparison
Partners PrEP FTC/TDF arm
81% 75%
TDF2 79% 62%
iPrEx 51% 44%
FEM-PrEP 26% 6%
Donnell et al CROI 2012
Grant et al N Engl J Med 2010
Van Damme et al CROI 2012
Paxton et al FDA 2012
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Adherence Summary Unannounced Pill
Count MEMS Clinic Pill Count Self Report
N Mean (SD) Median
(IQR)
Mean
(SD)
Median
(IQR)
Mean
(SD)
Median
(IQR)
Mean
(SD)
Median
(IQR)
Overall 1,03
9
97.6
(6.3)
99.1
(96.9-100)
86.9
(16.4)
92.1
(85.9-94.2)
96.6
(6.7)
98.8
(96-99.8)
98.2
(3.8)
99.4
(98-100)
By gender
Female 490 98.2
(5.1)
99.3
(97.5-100)
89.6
(12.4)
92.9
(88.4-94.6)
97.4
(6.1)
99.1
(97-100)
98.4
(3.9)
99.5
(98.3-100)
Male 549 97.1
(7.2)
98.8
(96.2-100)
84.6
(19)
91.2
(83.5-93.6)
95.9
(7.2)
98.4
(95.5-99.6)
97.9
(3.8)
99.2
(97.6-100)
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PrEP Efficacy
• HIV-1 infections
– 14 in 404 participants on placebo (333 person-years)
– 0 infections in 750 participants on active drug (616
person-years)
• PrEP efficacy within this adherence sub-study was
100% (95% CI 87-100%)
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PREP adherence is
opportunity to
mitigate tension
and strengthen
relationship
“Discordance
dilemma”
Excellent Adherence PrEP Adherence Explained by
Relationship Dynamics Ware et al JAIDS 2012
PrEP Resolves Tension in a Committed HIV Discordant
Sexual Relationship
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PREP adherence is
opportunity to
mitigate tension
and strengthen
relationship
“Discordance
dilemma”
Excellent Adherence PrEP Adherence Explained by
Relationship Dynamics Ware et al JAIDS 2012
PrEP Resolves Tension in a Committed HIV Discordant
Sexual Relationship
Love
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PREP
nonadherence
becomes
mechanism to
express discord
PREP is a reminder
of “discordance
dilemma” in setting of
mistrust or threat to
the relationship
Corollary: Relationship Discord Threatens
PrEP Adherence Ware et al JAIDS 2012
PrEP Can Create Tension in a Previously Committed HIV
Discordant Sexual Relationship
Discord
and
Distrust
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PrEP Adherence During Relationship
Discord and Distrust
Courtesy of Fran Priddy IAVI
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Relationship Support and PREP Adherence
Ware and Bangsberg JAIDS 2011
Treatment
Adherence
Structural &
economic
barriers
Routine Barriers
Medication side effects
Depression
Substance use
Memory
Stigma
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Relationship Support and PREP Adherence
Ware and Bangsberg JAIDS 2011
Relationship
Support
Treatment
Adherence
Structural &
economic
barriers
Routine Barriers
Medication side effects
Depression
Substance use
Memory
Stigma
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Africans “don’t know what Western time
is,”and “do not know what you are talking
about,” when asked to take drugs at
specific times.
Andrew Natsios USAID Administrator
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How to Take ARVs on Time in Rural Uganda
Without a Watch: John’s Adherence Story Maier et al PLOS 2006
• No education
• Works as a farmer.
• Lives with his brother, sister-in-law, and three nieces in a three room mud-walled house without electricity.
• Owns a lantern, bed, sofa, bike, and a radio, but no watch.
• HIV in April 2005 and started generic D4T/3TC/NVP (Triomune) after disseminated herpes zoster and Kaposi’s sarcoma
• CD4 count of 151
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Electronic medication monitor record of time of
bottle openings for am and pm doses.
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Adherence
• 90% of doses within 10 minutes of 7:20
• 90% of doses within 17 minutes of 7:20
pm
• Overall adherence 98.9%
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John’s Adherence: 0-9 and 10-18 months
Initial MEMS assessment (August 2005
to April 2006 (9 months))
Subsequent MEMS assessment (May
2006 to January 2007 (9 months))
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Conclusions
• Humility – (we were wrong most of the time)
• Social context matters – Strength of social ties to partner, family, friends
– Impact of HIV on close social ties
• Reliable PrEP adherence by engaging stable committed partners
• Early ARV treatment may be more challenging
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Conclusions
• Humility – (we were wrong most of the time)
• Social context matters – Strength of social ties to partner, family, friends
– Impact of HIV on close social ties
• Reliable PrEP adherence by engaging stable committed partners
• Early ARV treatment may be more challenging
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Conclusions
• Humility – (we were wrong most of the time)
• Social context matters – Strength of social ties to partner, family, friends
– Impact of HIV on close social ties
• Reliable PrEP adherence by engaging stable committed partners
• Early ARV treatment may be more challenging
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Conclusions
• Humility – (we were wrong most of the time)
• Social context matters – Strength of social ties to partner, family, friends
– Impact of HIV on close social ties
• Reliable PrEP adherence by engaging stable committed partners
• Early ARV treatment may introduce new challenges
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manmanu
I”In sum, a well designed study and important contribution to the field
of nosocomial transmission of TB, but I strongly recommend that the
author find an editor whose first language is English.”
Anonymous reviewer
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Andrew Moss, PhD UCSF
Tom Coates, PhD UCLA
Bruce Walker, MD MGH/Harvard
Jessica Haberer, MD, MS MGH/Harvard
Peter Hunt, MD
Jeff Martin, MD
UCSF
UCSF
Conrad Muzoora, MD Mbarara University of Science and Technology
Anna Baylor, MD MGH
Steven Deeks, MD UCSF
Mwbesa Bwana, MD Mbarara University of Science and Technology
Connie Celum University of Washington
Norma Ware, PhD Harvard Medical School
Jared Beaton, MD, PhD University of Washington
Lloyd Marshall Wisepill, Cape Town
Acknowledgements
Funding
Mark and Lisa Schwartz Foundation, Bill and Melinda Gates Foundation
NIMH RO-1 54907; Michael Stirratt, PhD and Chris Gordon, PhD