Transcript Session 9 - Teaching Slides

Treatment Failure
HAIVN
Harvard Medical School AIDS
Initiative in Vietnam
Learning Objectives
At the end of this presentation, participants
should be able to:
• Recognize the importance of diagnosing
treatment failure
• Know the definitions of treatment failure
• Understand how to diagnose ARV treatment
failure based on clinical, immunological, and
virological criteria
• Recite the recommended second line regimens
after first line treatment failure in Vietnam
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Content
•
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•
•
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Overview
Treatment failure definitions
Diagnosing treatment failure
Changing to 2nd line
Case examples
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Overview
• The frequency of treatment failure among children
on ART in Vietnam is currently unknown.
• Studies from other settings (i.e. South Africa)
suggest a relatively high rate of treatment failure
 11% probability of treatment failure at three years
• When treatment failure occurs, it is often not
recognized
 Approximately 50% of children with virologic failure were
not switched to 2nd line therapy
 When switching occurred there was a significant delay
(median 5 months) between treatment failure and
switching
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Overview
• Proper and prompt recognition of
treatment failure is important:
 Prevent progression of disease and clinical
event (OI)
 Prevent accumulation of drug resistance
mutations
 Avoid unnecessary switching to secondline drugs
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Causes of treatment failure
• Problems with patient adherence
• Pre-existing or acquired drug resistance
• Problems with absorption or metabolism
of a drug leading to sub-therapeutic
drug levels; due to:
 inherent characteristics of the individual
 pharmacokinetic interactions with
concomitant medications
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HIV resistance: ARV Exposure
Drug concentration in blood
Changes of drug concentration in blood during treatment
Time
Failed to take
medication
Regular medication
Resistant HIV
Wild-type HIV
Lower limit of effective drug concentration in blood
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Before diagnosing treatment failure:
 ART > 6 months
 Currently adherent
 Not acutely ill
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If the patient (or care provider)
is not adherent:
• Counsel the patient (or care provider) on
adherence
• Evaluate the patient again after 3 months of
good adherence
 Clinical exam
 Repeat CD4 and/or VL if available
Consider switching to second line ARV only if
evidence of treatment failure persists while the
patient is taking ARV with good adherence
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CD4 Monitoring
• Check CD4 every 3-6 months.
• Every test must be reviewed and compared to
previous results.
 Develop a system for reviewing all CD4
test results
 Patients with dropping CD4:
• Consider other causes of low CD4
(acute OI, poor adherence)
• Evaluate for possible treatment failure
The CD4 test is like a số vế: you only get a
benefit if you check the numbers later!
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Types of Treatment Failure
• Virological Failure
• Immunological Failure
• Clinical Failure
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Virological Treatment Failure
• Definition:
 Increase of viral load (VL) caused by resistant virus
 Adult guidelines: VL > 5.000 copies/ml
 Pediatric threshold not defined
 If no evidence of clinical or immunological treatment failure,
then confirm virological failure with 2 VL tests at least one
month apart before switching to 2nd line ARV
• HIV PCR (VL) test:
 Number of HIV RNA copies per ml of plasma
 Available at some sites in the North and South
 Best test to assess treatment success or failure
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Immunological Treatment Failure
• Immunological failure: Decline in CD4 count
due to ongoing destruction of T cell
 CD4 count falls to or below the level of severe
immunodeficiency by age after initial recovery
response
 CD4 count falls rapidly below the level of severe
immunodeficiency by age (confirmed by at least
two consecutive measurements)
 CD4 count falls to or below the baseline CD4
count
 CD4 count falls below more than 50% of the peak
level
Vietnam MOH HIV/AIDS Treatment Guidelines, 2009.
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Clinical Treatment Failure
• Clinical Failure:
 Lack of or decline in growth rate in children who initially
respond to treatment
 Loss of neuro-developmental milestones or development of
encephalopathy
 Severe or recurrent infection or illness: Recurrence or
persistence of AIDS-defining conditions or other serious
infections.
• Notes:
 Before considering a change in treatment because of growth
failure it should be ensured that the child is receiving
adequate nutrition.
 Some stage III conditions (pulmonary and lymph node TB,
bacterial pneumonia) can occur even with complete
virological suppression and may not indicate treatment
failure*
*Vietnam MOH HIV/AIDS Treatment Guidelines, 2009.
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Making the decision to switch
to 2nd line ARV
Clinical
Laboratory
Management
Clinical
Stage 1 – 2
CD4 not
available
Do not switch
CD4
available
Consider switching only if at least 2 CD4 results
are below severe immunodeficiency level by age
CD4 not
available
Consider switching
CD4
available
Switch if CD4 is below severe immunodeficiency
level, especially if children have ever had good
immunological response to ART
CD4 not
available
Switch to 2nd line
CD4
available
Switch to 2nd line
Clinical
Stage 3
Clinical
Stage 4
Vietnam MOH HIV/AIDS Treatment Guidelines, 2009.
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Consider causes of treatment failure
• Assess medication adherence
 Inadequate adherence is the most common cause
of antiretroviral treatment failure
 Assess barriers to adherence
 Explore interventions to improve adherence
• Assess medication intolerance
• Assess issues related to pharmacokinetics
 Recalculate doses for individual medications using
weight or body surface area
 Identify concomitant medications including
prescription, private pharmacy, and traditional
therapies
 Assess for drug-drug interactions
Before switching to 2nd Line ARV…
• Repeat adherence counseling: only change
the ARV regimen when the patient has the
ability to take it with good adherence.
• Treat any acute OI first.
• Provide counseling and patient education
about the new regimen.
REMEMBER:
There is no 3rd line ARV regimen in Vietnam.
Second line ARV is last-line ARV!
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Switching from 1st line to 2nd
line regimens
Failure on 1st regimens
Change to 2nd regimens
AZT or d4T + 3TC + NVP ddI + ABC + LPV/r
AZT or d4T + 3TC + EFV
AZT or d4T + 3TC + ABC
ddI + EFV + LPV/r
ddI + NVP + LPV/r
ABC + 3TC + NVP or EFV AZT + 3TC (+/- ddI) + LPV/r
d4T + 3TC + LPV/r
Key Points
• It is important to recognize resistance and treatment
failure
• Always evaluate adherence before changing to second
line ARV
• There are 3 types of treatment failure: clinical,
immunological, and virological
• Viral load testing is the most accurate way of diagnosing
treatment failure
• If viral load not available, treatment failure can be
determined by a combination of clinical and/or
immunological criteria
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Thank you!
Questions?