Zambian HIV Guidelines:: Treatment Failure

	Zambia HIV National Guidelines
	Introduction HIV Counseling and Testing Sexually Transmitted Infections (STIs) General Principles of Antiretroviral Therapy for Chronic HIV Infection in Adults and Adolescents When to Start ARV Therapy for Chronic HIV Infection in Adults and Adolescents Initial Regimen for ARV Therapy Adherence Baseline evaluation and Monitoring Calculations: Ideal Body Weight, Body Mass Index and Creatinine Clearance ARV Therapy for Individuals with Tuberculosis Co-Infection Adverse Effects and Toxicity Immune Reconstitution Inflammatory Syndrome (IRIS) Changing or Stopping ART Treatment Failure Stopping ARV Therapy Post Exposure Prophylaxis Cotrimoxazole Prophylaxis WHO Staging in Adults and Adolescents Nutrition Care and Support Palliative Care in HIV and AIDS
	Guide Editors
	Editor In Chief Joel E. Gallant, MD, MPH Pharmacology Editor Paul Pham, PharmD, BCPS Zambia Guideline Team Peter Mwaba MMed PhD FRCP Alywn Mwinga MMed Isaac Zulu MMed MPH Velepie Mtonga MMed Albert Mwango MBChB Jabbin Mulwanda MMed FCS

Guidelines>Zambia HIV National Guidelines>

Treatment Failure

05-06-2008

Clinical Failure

Clinical disease progression signalled by new or recurrent WHO Stage 3 or 4 condition when ART has been given sufficient time to induce protective degree of immune restoration (>6 months). Often associated with weight loss and drop in hemoglobin
Exclude IRIS. IRIS not indication for changing ART
Virologic failure occurs first followed by immunologic and then clinical failure.

Immunologic failure

Fall in CD4 count to 50% of peak value on treatment OR decline to pre-therapy baseline or below OR persistent CD4 count below 50 after 12 months on therapy.
If CD4 increase <50 at 6 months review patient and consider treatment failure.
When ART started with advanced disease, may take longer to see clinical or immunologic improvement; in some cases patients may never achieve substantial CD4 increase

Virologic failure

When VL testing available, VL >400 after 6 months on therapy suggests failure
Blips (single VL 50-1000) not considered failure; repeat VL as soon as possible
In patients who appear to be failing with undetectable VL, consider undiagnosed OIs or other concomitant illnesses.

Factors Leading to Treatment Failure

Poor adherence
Prior exposure to ART with development of resistance
Primary viral resistance (infection with resistant strain)
Inadequate drug absorption
Suboptimal dosing (e.g., sharing drugs, cutting dose because of side effects)
Inadequate or inconsistent drug supply

Clinical Disease Progression as Indicator of Treatment Failure (T-Staging)

Clinical events occurring in first 6 months of therapy often represent IRIS related to pre-existing conditions and are excluded from definition of clinical failure. New or recurrent WHO stage 3 or 4 conditions after 1st 6 months of treatment with good adherence considered functional evidence of disease progression. Referred to as T-staging (T=staging event whilst on treatment). Table below indicates how clinical staging on ART can be used as indicator of failure prompting consideration of need to switch therapy.

Asymptomatic (T1) ^a
Recommendation: Do not switch regimen
Maintain scheduled follow-up visits, including CD4 monitoring (if available)
Continue to offer adherence support
Stage 2 event (T2) ^a
Recommendation: Do not switch regimen^b
Treat and manage staging event
Assess and offer adherence support
Check if on treatment for at least 6 months
Assess continuation or reintroduction of OI prophylaxis
Schedule earlier visit for clinical review and consider CD4 (if available)^c
Stage 3 event (T3) ^a
Recommendation: Consider switching regimen^b,d
Treat and manage staging event and monitor response
Assess and offer adherence support
Check if on treatment for at least 6 months
Check CD4 cell count (if available)^c,d
Assess continuation or reintroduction of OI prophylaxis
Institute more frequent follow-up
Stage 4 event (T4) ^a
Recommendation: Switch regimen^b,e
Treat and manage staging event and monitor response Check CD4 cell count (if available)^c
Check if on treatment for at least 6 months
Assess continuation or reintroduction of OI prophylaxis
Assess and offer adherence support

Footnotes

a. Refers to clinical stages while on ART for at least 6 months (termed T1, T2, T3, T4).

b. Differentiation of OIs from IRIS necessary.

c. Treat and manage staging event before measuring CD4 count.

d. Certain WHO clinical stage 3 conditions (e.g. pulmonary TB, severe bacterial infections) may be indicators of treatment failure and thus require consideration of 2nd-line therapy; response to appropriate therapy should be used to evaluate need for switching therapy.

e. Some WHO clinical stage 4 conditions (lymphatic TB, uncomplicated TB pleural disease, oesophageal candidiasis, recurrent bacterial pneumonia) may not be indicators of treatment failure and thus do not require consideration of 2nd-line therapy.

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