UPDATE ON ANTIRETROVIRAL UPDATE ON ANTIRETROVIRAL

THERAPY IN CHILDRENTHERAPY IN CHILDREN

Dr. Agnes Langat,

Paeditrician.

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BackgroundBackground

� HIV disease is rapidly progressive in young children

� Children surviving to older ages tend to have slower disease progression

� Early recognition and diagnosis enables early treatment and better outcomes.

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Antiretroviral Drug TherapyAntiretroviral Drug Therapy--

ScopeScope

Unit 1: Initiation and first line regimens of ART in children

Unit 2: TB/HIV management

Unit 3: Common ARV Adverse Effects and their management with special emphasis on lactic acidosis

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ObjectivesObjectives

� Explain the goals of and the process of initiating antiretroviral therapy.

� Highlight the new ART National guidelines

� Manage HIV positive children who have TB co-infection.

� Outline ARV drug adverse effects with emphasis on lactic acidosis.

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Initiation and first line Initiation and first line

regimens of ART in childrenregimens of ART in children

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CRITERIA FOR ART CRITERIA FOR ART

INITIATIONINITIATIONFirst confirm the HIV diagnosis

Child < 18 months: Positive HIV virologic test (HIV PCR – dried blood spot DNA PCR or whole blood RNA PCR)

OR if cannot do PCR: Make presumptive WHO stage 4 clinical diagnosis (next slide)

Child > 18 months: Positive HIV antibody test (rapid test or ELISA)

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WHO Presumptive Clinical Stage 4 WHO Presumptive Clinical Stage 4

(age < 18 mths)(age < 18 mths)� For a symptomatic HIV-antibody positive infant age <18 mths, make a presumptive diagnosis of severe HIV disease (clinical stage 4) when*:

a) Two or more of the following are present:

� Oral candidiasis/thrush

� Severe pneumonia

� Severe Sepsis

OR

b) Diagnosis of any AIDS-indicator condition(s) can be made (see full stage 4 list)

Other supporting evidence: recent HIV-related maternal death or advanced HIV disease in the mother; and/or CD4 <25%

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Criteria for ART InitiationCriteria for ART Initiation

There are two broad criteria to consider prior to ART initiation

� Medical criteria

� Psychosocial criteria

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MEDICAL CRITERIA FOR ART MEDICAL CRITERIA FOR ART

INITIATIONINITIATION

Children less than 18 months

� Start ART as soon as possible after diagnosis of HIV

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MEDICAL CRITERIA FOR ART MEDICAL CRITERIA FOR ART

INITIATIONINITIATION

Children above 18 months

� WHO stage 3 or 4 disease (irrespective of CD4 counts or %).

� Low CD4 count or percentage (irrespective of WHO stage):

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NASCOP (Kenya) 2008 Criteria for NASCOP (Kenya) 2008 Criteria for

initiating ART in childreninitiating ART in children

Age in months < 18 mth 18–59 mth 5 yr +

By CD4 % ALL < 25% < 20%

By CD4 count ALL < 1500 < 350

By WHO clinical

Stage

ALL 3 or 4 3 or 4

Child fulfilling any of the above criteria needs ART.

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NASCOP (Kenya) Compare 2006 with NASCOP (Kenya) Compare 2006 with

2008 Criteria2008 Criteria

Age in months < 18 mth 18–59 mth 5 yr +

By CD4 % ALL

(< 25%)

< 25%

(< 20%)

< 20%

(< 15%)

By CD4 count ALL

(< 1500)

< 1500

(< 750)

< 350

(< 250)

By WHO clinical Stage

ALL

(3 or 4)

3 or 4 3 or 4

Psychosocial Criteria for ART Psychosocial Criteria for ART

InitiationInitiation

� Identifiable parent or guardian able to understand the regimen, and consistently administer the child’s medication.

� Ability to regularly attend the HIV clinic appointments.

� Sustainable long-term access to antiretroviral drugs (either through programs providing ART, or financially able to purchase ARV drugs).

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Preparing a child for ARTPreparing a child for ART

Prior to initiating ART, the following preparations should take place

� Medical Preparation

� Psychological Preparation

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Preparing a child for ARTPreparing a child for ART

Medical Preparation� Baseline tests to check haematological, liver and kidney function:◦ Full blood count (resources limited, do Hb)◦ Liver function tests (resources limited, do alanine transaminase or ALT)◦ Renal function tests (resources limited, do serum creatinine)

� Do baseline CD4 if possible� Do baseline viral load (RNA PCR – not SOP for KNH)

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Preparing a child for ARTPreparing a child for ART

Medical Preparation (continued)

� Baseline clinical assessment including weight, height, surface area.

� If current TB suspected, investigate for TB (If TB confirmed, consider delaying ART initiation until child completes 2-4 wks of anti-TB treatment)

� Initiate co-trimoxazole prophylaxis. Treat any inter-current illnesses

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Preparing a child for ARTPreparing a child for ART

Counselling Preparation

� Take time to counsel, prepare, educate the family

� Older child - disclose HIV status to child

� Give tips/guidance on how to adjust daily schedule to improve ability to adhere

� Special counseling relevant to specific situations (orphans, child-headed households, foster parents) should be given

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Counselling Counselling -- Health EducationHealth Education

� Goals, limitations and side effects of ART

� Lifelong nature of therapy and importance of adherence to ART and to clinic appointments

� When and how to administer the drugs� Possible adverse effects and how to recognize and deal with them.

Do not over-emphasize the last issue – don’t scare guardian!

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Goals of ARV TherapyGoals of ARV Therapy

� Clinical: Reduce HIV related Morbidity & Mortality.

� Immunological: Restoration and preservation of immune function.

� Virological: Maximal and durable suppression of HIV replication.

Improve quality of life!

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Special ConsiderationsSpecial Considerations

Relative contraindications to ART include:

� Hepatic insufficiency

� Renal insufficiency.

Correct these prior to treatment initiation

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Selecting ARV RegimensSelecting ARV Regimens

General Rules

� Always use 3 drugs together

� First 2 drugs should be NRTI class (nucleoside backbone)

� 3rd drug should be of a different class, preferably NNRTI

� (In special situations, such as previous nevirapine exposure, use PI)

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What ARV Drugs to Start What ARV Drugs to Start 11stst line therapy (NASCOP 2008)line therapy (NASCOP 2008)

Age < 3 years

� Zidovudine (AZT) or Abacavir (ABC) + Lamivudine (3TC) + Nevirapine (NVP)

Age > 3 years and over 10kg

� Zidovudine (AZT) or Abacavir (ABC) + Lamivudine (3TC) + Efavirenz (EFV) or NVP.

These can be taken with or without food, taste is acceptable, and all are stable at room temp.

Stavudine use only as last choice due to toxicity

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First Line Regimen in NVPFirst Line Regimen in NVP--Exposed Exposed

Child (NASCOP 2008)Child (NASCOP 2008)

� Child exposed to single dose Nevirapine for PMCT may have NVP resistant virus. Avoid NNRTIs in their 1st line regimen

� AZT or ABC + 3TC + LPV/r

(However, NVP may still be used if LPV/r is not available)

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ART AND TUBERCULOSISART AND TUBERCULOSIS

Rifampicin interacts with nevirapine and most P.I’s

Start anti-TB treatment immediatelyStart ART 2-8 weeks after initiating anti-TB treatment using the following regimen:

� AZT or ABC + 3TC + EFV if above 3 years

� AZT or ABC + 3TC + ?? NVP if below 3 years

Child < 3 yr – No really good option available. Triple NRTI undesirable regimen. Research ongoing.

Increase NVP dose by 30% and monitor closely for toxicity.

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Changing ART and Second line Changing ART and Second line

regimensregimens

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Indications for change of therapyIndications for change of therapy

FIRST CHECK ADHERENCE!!

Clinical indications

� Progressive neurodevelopmental deterioration

� Growth failure

� Disease progression – new OI, or move from one stage to next

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Indications for change of therapyIndications for change of therapy

Immunologic indications

� Drop of CD4 by more than half of peak value attained after ART initiation;

� Decline of CD4 to below severe immunosuppression threshold level (age-specific)

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Indications for change of therapyIndications for change of therapy

Virologic indications

� Persistent increase in viral load (confirmed by 2 tests)

� (Adolescents only; HIV RNA not suppressed to undetectable levels after 6 months ART)

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Why is regimen failing?Why is regimen failing?

� Poor adherence?

� Pharmacokinetic reasons: drug-drug interactions; food interaction issues

�Viral resistance

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Second line therapy Second line therapy

� Change ALL 3 DRUGS

� Replace the NRTIs with two new NRTIs (new nucleoside backbone)

� Replace the NNRTI with a PI

� If first line regimen included a PI, replace it:

◦ with an alternative PI (ritonavir-boosted)

◦ or if no previous NNRTI exposure, replace PI with an NNRTI

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Second line therapySecond line therapy

(cont)(cont)

� If initial problem was adherence to therapy, must address this first. If can’t adhere, withdraw therapy altogether.

� Review patient medications as you assess adherence

� Consider overlap in resistance

� Consider and discuss quality of life issues especially if complex new regimens to be used

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Kenya national recommended 2Kenya national recommended 2ndnd

line ART in childrenline ART in children

First line� AZT/3TC/NVP or EFV

� d4T/3TC/NVP or EFV

� AZT/3TC/Kaletra

� ABC/3TC/NVP or EFV

Second line

� ABC/ddI/ LPV/r or

� ABC/ddI/ LPV/r

� ABC/ddI/ PI/ritonavir

� AZT/ddI/ LPV/r

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Common ARV Drug adverse Common ARV Drug adverse

effects and their managementeffects and their management

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ARV adverse events principles of ARV adverse events principles of

managementmanagement� Rule out other medication as causes.

� Consider other disease processes.

� Mild reaction (grades 1-2)*: continue and monitor.

� Severe reaction (grade 3-4)*: discontinue regimen

◦ Stop all drugs till event is over then modify regimen OR

◦ Single drug substitution. single drug substitution may suffice d4T for AZT; or EFV for NVP

* Refer to ANECCA Handbook Appendix E for grading of adverse events

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Lactic AcidosisLactic Acidosis

� Possible Offending drug - All NRTIs

� Clinical Presentation - Generalized fatigue,GI symptoms, sudden unexplained weight loss, tachpnoea, dyspnoea

� Lab definition◦ Lactic acid ≥ 5 mmol/l

� Management◦ Discontinue ARVs

◦ Supportive therapy

◦ Start on a NNRTI and PI based regimen and possible ABC

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ASANTE

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ASANTENI !

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