Transcript Pub Hlth Use of HIVDR data - World Health Organization

Uses of Data from the WHO HIV Drug
Resistance Strategy:
1.
Monitoring of HIVDR emerging in treated
groups in sentinel ART clinics
HIV Drug Resistance Team
World Health Organization
1
Goal
Monitor HIVDR emerging in cohorts starting ART at
sentinel clinics, and associated ART program factors, in
order to assist ART program planning and maintain
effectiveness of first-line ART regimens
Context: ART program evaluation of HIVDR
prevention/emergence of HIVDR and associated ART
program factors
Objectives
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Estimate the proportion of the ART site population
achieving HIVDR prevention as measured by viral load
suppression, 12 months after starting first-line ART
Genotype specimens to identify specific HIVDR mutations
and mutation patterns in patient groups not achieving
prevention of HIVDR.
Collect and analyze data on ART programme factors
potentially associated with the prevention (or nonprevention) of HIVDR
Use results to plan for further programme evaluation if
necessary, to support optimal ART programme functioning
at sentinel sites, to apply lessons learned to other
programme sites, and to support planning and decision
making to optimize ART effectiveness
Monitoring of HIVDR emerging in treatment
Cohorts beginning ART at sentinel sites followed for 12 months
Blood draw for viral load and genotyping at baseline, and at
regimen switch or 12 months (may extend to 24/36 months)
 Outcome measures: viral suppression (prevention of HIVDR
emergence) and genotype
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– HIVDR mutations evaluated if viral load is detectable
Potentially associated factors (adherence, drug supply,
subtype, previous antiretorivral (ARV) drugs, ART regimen)
evaluated
 Evidence-based recommendations, and lessons learned for
other ART programs, to be disseminated by the HIVDR
working group
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Monitoring: Inclusion and Exclusion Criteria
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Inclusion Criteria:
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Individuals initiating adult first-line ART at participating
sentinel sites, regardless of age*
Exclusion Criteria:
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Individuals previously taking first-line ART at the
sentinel monitoring site
Individuals transferring in from another ART delivery
site on a first-line regimen
* Paediatric monitoring protocol is also avialable
Potentially-associated ART clinic factors
(independent variables: minimum dataset)
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Individual Patient Factors*
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Aggregate Site Factors:
– Previous ARV exposure (PMCT, HIV mono or dual-therapy,
partner's ARVs, informal sector ARVs) before first-line ART
– Baseline HIVDR mutations
– Drug pick-up % of expected
– Adherence to first-line ART
– ART clinic attendance % of expected
– HIV-1 subtype
– Drug supply continuity
– Prescribing practices
– Drug quality (if assessed as part of program monitoring)
*Additional factors such as other clinical conditions, other medications may be
collected if available
Prospective Cohort: Definition of Time Points
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TIME 1 (Baseline): Time of commencement of first-line ART
TIME 2 (Endpoints):
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Still on first line ART regimen at 12 months*
Switch: Change to second line regimen before 12 months
Stop: ART ends and patient continues in care at clinic for at least 30 days after
ART ends, no resumption of first-line ART before 12 months from original ART start
date (no prescription or no drug pick-up for two months before 12 months from
original start date or report of no ARV drugs taken for 30 days before 12 months
from original start date)
Loss to to follow-up: Break in appointment keeping and drug pick up; no return to
clinic before 12 months
Death during first 12 months after start of first-line ART
Transfer out: Transferring care from the HIVDR monitoring site to another ART
delivery site, still on first line ART
*Patients experiencing a Substitution, that is, removal of one drug from a first line regimen and substituting another,
are still considered to be on first line ART at 12 months if they do not reach another endpoint.
Outcomes at 12 months or earlier endpoint
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Undetectable viral load at Time2 Ξ Prevention of HIVDR*
Classification of outcomes in those lacking evidence of HIVDR
prevention:
Detectable viral load + "resistant" genotype at Time2 Ξ HIVDR
Detectable viral load + "susceptible" genotype at Time2 Ξ
potential HIVDR
Lost to follow-up, Stop Ξ potential HIVDR
Transfer out, death Ξ not relevant, remove from numerator and
denominator
*Viral load suppression defines HIVDR prevention for the purposes of
HIVDR sentinel monitoring
HIVDR Monitoring Sample Size
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“Effective” sample size of 96 (N = 96 + number of
expected deaths + number of expected transfers out)
guarantees a maximum width of a 95% CI +/- 10%
regardless of the cumulative incidence of viral
suppression
 The first consecutive eligible N individuals presenting
for ART on and after the start date are selected for
sentinel HIVDR monitoring
 Point estimate is used to classify the proportion of
viral suppression (ΞHIVDR prevention) as being
above or below 70%
Blood Draw for genotyping
Blood Draw for genotyping + viral load
Suppressed viral load
LTFU
stop
Time1
Time2
ART 1
12
Months
If still on
1st line
Time2
Switch
Outcomes
Death*
Resistance
Potential resistance
Prevention of resistance
HIVDR muts not seen
Detectable viral load
Transfer out*
Transfer out*
Omitted from
numerator and
denominator
Detectable HIVDR mutations
Data Sources
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Capture of routine data:
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Additional data collected for HIVDR monitoring
– HIV CARE/ART CARDS or medical records: previous ARV**,
start date, prescriptions, drug pick-up, regularity of
appointment keeping, pill counts**, endpoints (death, loss to
follow-up, transfer out on 1st-line regimen, substitution, stop,
switch of regimen)
– Pharmacy records
– Genotyping: residual blood specimen: Time1 (Baseline) and
Time2 (12 months or regimen switch) + viral load at Time2
– If needed, minimal supplemental questions at Time1 + Time2
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**previous ARV and pill counts abstracted if available
Key HIVDR Monitoring results
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% achieving HIVDR prevention after 12 months of ART
(suggested target: >70% "HIVDR prevention")
Among those NOT achieving prevention: Description of
HIVDR mutations and mutation patterns
Assess association between levels of HIVDR prevention
and HIVDR mutation patterns with:
a)
b)
c)
d)
e)
previous ART
drug pick-up regularity
appointment keeping
adherence
baseline mutations
a)
b)
c)
HIV-1 subtypes
Drug supply continuity
Prescribing practices
For analysis of more than one site's data, also assess
association with:
Public Health Implications of results:
HIVDR prevention
1. >70% HIVDR prevention:
– Evaluate for important lessons learned which can be qualitatively
generalized to other sites
– Encourage ongoing programme evaluation
2. < 70% HIVDR prevention:
– May be associated with aggregate site factors, individual patient
factors – both should be addressed by identifying elements of the
ART programme which require increased support or change
– HIVDR team should identify barriers to HIVDR prevention that
affect other clinics
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Drug supply discontinuities
Non-standard prescribing
Previous ARV experience among those starting first-line ART
Programmatic factors associated with lack of access or nonadherence, loss to follow-up
– Evaluate program monitoring information or initiate program
monitoring in other clinics
– Address probable problems
Public Health Implications of results:
HIVDR mutation patterns
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Recommendations for action depend upon mutations
seen and their distribution + patterns. Examples of
action include:
If specific mutations are associated with PMTCT or other
previous ART, consider (on a population basis) alternate
regimens for individuals with specific histories
If specific mutations are associated with particular
prescribing practices, consider training or other
measures to standardize prescribing
Depending on the patterns, consider implications for
standard first and second-line regimens currently in use
If indicated, develop research strategies to study
questions in depth
Multi-site and multi-country analyses
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Multi-site and multi-country analyses may be possible
To evaluate the association between independent
variables and viral suppression/resistance patterns
Monitoring results may generate hypotheses to be tested
by supplemental research projects
Examples: association between HIVDR prevention or
resistance patterns and
– Previous PMTCT or previous “non-medical ARV”
– Prescribing patterns
– Interruptions in drug supply
– Simple adherence measures (keeping appointments)
– Interaction between HIV-1 subtypes + ARVS
Summary of uses for results
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Will allow national HIVDR working group to identify and
describe good ART practices or needed improvements in
ART sites to limit HIVDR :
– Program monitoring, prescribing practices, follow-up, support for
adherence and ART access, assurance of uninterrupted drug
supply
Inform policy decisions at national and global levels on
effectiveness of first line regimens and composition of
second-line regimens
 Reinforce programme practices and ART programme
monitoring recommended as part of overall WHO treatment
strategy
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Key HIVDR Monitoring Results
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Evaluate whether sentinel programs achieve >70%
"HIVDR prevention" after 12 months of ART
Among isolates with detectable virus: Describe
HIVDR mutations and mutation patterns
Assess association between levels of HIVDR
prevention and mutation patterns with:
– Previous ARV experience
– Prescribing practices
– Drug pick-up regularity
– Appointment keeping
– Continuity of drug supply
– Pill count (if routinely performed at site)
– Adherence scale question
Summary of current WHO language
on uses of results
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Will allow national HIVDR working group to identify and
describe good ART practices or needed improvements in
ART sites to limit HIVDR :
– Program monitoring, prescribing practices, follow-up, support for
adherence and ART access, assurance of uninterrupted drug
supply
Inform policy decisions at national and global levels on
effectiveness of first line regimens and composition of
second-line regimens
 Reinforce programme practices and ART programme
monitoring recommended as part of overall WHO treatment
strategy
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Examples: HIVDR suppression
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Low % HIVDR suppression associated with
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Low % HIVDR suppression, no particular associations
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High % HIVDR suppression
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poor drug supply continuity, or
previous ARV use, or
Poor appointment-keeping, or
Poor drug pick-up, or
Poor reported adherence, or
Specific subtype
Aberrant prescribing practices, or
Drug supply discontinuities
– Data suggests possible association but sample too small
– Data suggests no particular associations
– "good" indicators (> 80% adherence, drug pick-up, etc.)
– despite high % previous ARV use
– despite high % poor reported adherence
Examples: HIVDR patterns
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Resistance to specific drug or drug class associated
with:
– Previous ARV
– Specific HIV-1 subtype
– Demographic variable (risk group, gender, ethnic group,
residence area, clinician)
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High % of resistance to specific drug or drug class with
no clear associations
Low % HIVDR suppression but very few isolates with
any resistance mutations
Recommendations (general)
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Will probably always include the word "consider"
Should specify additional data needed for the
considerations
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Which groups or experts should review the data with
national HIVDR working groups to make
recommendations?
To which groups should recommendations be made?
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National Recommendations
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Recommendation categories within a country:
– Research studies to answer a specific question
– Enlargement of cohort size or number of sentinel sites to answer a
specific question
– Extension of the methodology to Year 2/3
– Consideration of changes to optimize ART program practices
• Training, support to staff, follow-up, clinic hours, financial or other
support to increase access
• Additional methods to monitor individual patients and take specific
actions for individuals based on results
– Consideration of changes in standard first-line ART regimens for specific
subgroups, all new patients in the clinic, all new patients in the area, all
new patients in the country
– Consideration of changes in the second line regimens for any of these
– Consideration of additional monitoring of or changes in ART program
practices
– Others?
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Which scenarios would prompt a definite recommendation in one
of these categories?
Regional/global recommendations
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Recommendation categories on the international level:
– Research studies to answer a specific question
– Enlargement of cohort size or number of sentinel sites in multiple
countries to answer a specific question
– General extension of the methodology to Year 2/3
– Consideration of multi-country support to optimize ART program practices
• Training, support to staff, follow-up, clinic hours, financial or other
support to increase access
• Additional methods to monitor individual patients and take specific
actions for individuals based on results
– Consideration of changes in standard first-line ART regimens for specific
subgroups, specific region(s), all resource-limited countries
– Consideration of changes in the second line regimens for any of these
– Consideration of additional monitoring of or changes in ART program
practices
– Others?
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Which scenarios would prompt a definite recommendation in one
of these categories?