Treatment Failure

HAIVNHAIVNHarvard Medical School AIDS

Initiative in Vietnam

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Learning ObjectivesAt 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

• 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

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 second-

line 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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Lower limit of effective drug concentration in blood

Regular medication Wild-type HIVResistant HIV

Drug concentration in blood

Failed to take medication

Changes of drug concentration in blood during treatment

TimeFailed to take medication

Time

HIV resistance: ARV Exposure

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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 ManagementClinical

Stage 1 – 2CD4 not available

Do not switch

CD4 available

Consider switching only if at least 2 CD4 results are below severe immunodeficiency level by age

Clinical Stage 3

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

Clinical Stage 4

CD4 not available

Switch to 2nd line

CD4 available

Switch to 2nd line

Vietnam MOH HIV/AIDS Treatment Guidelines, 2009.

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

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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!

Switching from 1st line to 2nd line regimens

Failure on 1st regimens Change to 2nd regimens

AZT or d4T + 3TC + NVPAZT or d4T + 3TC + EFV

ddI + ABC + LPV/r

AZT or d4T + 3TC + ABC ddI + EFV + LPV/rddI + NVP + LPV/r

ABC + 3TC + NVP or EFV AZT + 3TC (+/- ddI) + LPV/rd4T + 3TC + LPV/r

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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

Thank you!

Questions?