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Treatment Failure

HAIVNHarvard Medical School AIDS

Initiative in Vietnam

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Learning Objectives

By the end of this session, participants should be able to:

Identify the 3 types of treatment failure Explain how to diagnose treatment

failure based on clinical, immunological, and virological criteria

Explain the indications for viral load testing in Vietnam and interpret a viral load result

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Overview

Estimated frequency of treatment failure in Vietnam is 2-3% in first year of treatment, based on clinical and immunological criteria• Highest incidence among patients who took

ARVs before enrolling in free ARV program Changing treatment to second line on

basis of virological or immunological failure aims to prevent clinical progression

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Resistance Overview (1)

Low levels of drug (caused by nonadherence) or low drug potency (caused by previous resistance) allow viral replication, which generate mutations in viral RNA and DNA

New mutations arise and these mutations can confer resistance to current drug

Resistant virus will preferentially multiply, gradually leading to treatment failure

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Resistance Overview (2)

Pre-Treatment

Initial Response

ARV Treatment

Wild type HIV Resistant HIV

Adherence Problem

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Three Types of Treatment Failure

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Typical Order of Treatment Failure

ClinicalFailure

ImmunologicFailure

VirologicFailure

ClinicalFailure

Immunological Failure

Virological Failure

This is the only part that you “see” (without lab tests)

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Clinical Treatment Failure

MOH criteria:• New or recurrent WHO stage IV event

Note: • Must differentiate from IRIS• Some stage 4 conditions can occur even

with complete virological suppression and may not indicate treatment failure while some stage 3 conditions may indicate treatment failure

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Immunological Treatment Failure

MOH Criteria: (at least 2 CD4 measurements)• CD4 count falls to or below pre-treatment

value• CD4 count falls to or below 50% on-

treatment peak value• CD4 persistently below 100 cells/uL for 1

year Other causes of change in CD4 must be

considered

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CD4 Monitoring

Check CD4 every 3-6 months Develop a system for reviewing all

CD4 count to review and compare every test to previous results

The CD4 test is like a lottery ticket:

you only get a benefit if you check the numbers later!

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Virological Treatment Failure

MOH criteria: VL > 5.000 copies/ml Confirm virological failure with 2 VL

tests at least one month apart before switching to 2nd line ARV

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Viral Load (VL) Test

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Viral Load Test – Definition

HIV PCR (VL) test:• Number of HIV RNA copies per ml of

plasma• VL testing will be supported in some

provinces in Vietnam

Best test to assess treatment success or failure

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Viral Load Test - Best Test to Assess Treatment

Effectiveness 2008 HCMC study of ARV resistance in

patients with 1st-Line treatment failure 248 patients had VL testing June-

December 2007• 96% on 1st line regimens

(d4T/AZT + 3TC + NVP/EFV)• Results:

VL undetectable: 100 (41.5%) VL detectable: 148 (58.5%)

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Targeted Viral Load

Objectives:• Confirm suspected clinical or

immunological failure• Maximize clinical benefits of first-line

therapy• Reduce unnecessary switching to second-

line therapy WHO now recommends use of viral load

to confirm treatment failure A targeted viral load strategy will be

supported in Vietnam

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When to Do the VL test?

After you make sure that patient has:• Been on ARV > 6 months• Adequate adherence

Do the VL test if patient presents with one of the following:• Clinical treatment failure criteria• Immunological treatment failure criteria• Other conditions or risk factors suspecting

treatment failure

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Interpretation of Viral Load

The results of VL Test will be one of these:

Note: Depends on the machine used for VL test, the detectable level can be 250 or 48

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What to Do if VL Result Is Undetectable?

Interpretation: •VL suppressed•Treatment failure is not confirmed

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Interpretation: Detectable but below threshold for confirming treatment failure

What to Do if VL Result Is Low Detectable?

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What to Do if VL Result Is > 5000?

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3 Steps to Diagnose Treatment Failure

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Clinical Practice: 3 Steps to Diagnose Treatment Failure

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Clinical Practice: Step 1 (1)

If patient is not adherent? Counsel the patient on adherenceEvaluate the patient again after 3 months of good adherence:

• Clinical exam• Repeat CD4 and/or VL if available Consider switching to 2nd line only if

evidence of treatment failure persists while patient is taking ARV with good adherence

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Clinical Practice: Step 1 (2)

Does patient have an acute OI? Acute OI such as TB can temporarily

decrease the CD4 count Therefore, before considering

switching to second line ARV:• Treat the OI first• Then reassess the clinical and

immunological status of the patient.

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Clinical Practice: Step 2

Clinical failure

New or recurrence of stage 4 diseases or conditions

CD4

failure c

CD4 count returns to or falls below pre-therapy baseline level

50% decline from the on-treatment peak value since the initiation of ART (if known)

CD4 count < 100 cells/mm3 after a year without any increase

Virological failured

VL > 5,000/ml

Check patient based on MOH Criteria for Treatment Failure

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Clinical Practice: Step 3 – Making a Decision

CriteriaClinical Stage

1 - 2 3 4

CD4 failure(VL testing not available)

• Do not switch ARV regimen

• Follow for appearance of clinical manifestations of treatment failure

• Repeat CD4 after 3 months

Consider switching to 2nd line ARV

Switch to 2nd line ARV

CD4 and VL failure Switch to 2nd line ARV

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If Patient Is Confirmed with Treatment Failure, What to Do?

Before Switching to 2nd Line ARV: Repeat adherence counseling Treat any acute OI first Provide counseling and patient

education about the new regimen

Second line ARV is last-line ARV in Vietnam!

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Switching ARV Due toTreatment Failure

1st Line ARV 2nd Line ARV

TDF + 3TC + NVP/EFVAZT + 3TC

or ddI + ABC

+ LPV/rAZT/d4T + 3TC + NVP/EFV

TDF + 3TCor

ddI + ABC

AZT/d4T + 3TC +TDF/ABC EFV/NVP + ddI

Vietnam MOH, HIV/AIDS

Treatment Guidelines, 2009.

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CASE STUDY

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Key Points

Important to recognize resistance and treatment failure

Three types of treatment failure are: clinical, immunological, and virological

Always evaluate patient’s adherence before changing to second line ARV

Diagnose treatment failure through:• VL testing (most accurate)• If VL not available, use combination of

clinical and/or immunological criteria

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Thank you!

Questions?