Paediatric First line ART Initiation and Follow-up

Paediatric First line ART: Initiation

Session Objectives
At the end of the session, we will understand

Provision of ART to children with HIV based on the national guidelines

When, how and what to start ART in children

When, how and what to start ART in TB and HIV co infected children
Appropriate Prescriptions: ART formulations with appropriate dosages Process of Monitoring and follow up after ART initiation
Paediatric First line ART: Initiation

Pre-ART Care
How will you assess the child after the diagnosis of HIV is confirmed? How will you manage the child?

Paediatric First line ART: Initiation

Pre-ART Evaluation and Follow up

Clinical Evaluation - Baseline and at every visit:
Clinical Evaluation Weight; Height; BMI; Head circumference Nutritional status and needs Opportunistic Infections: Clinical staging Treatment needs Prevention; prophylaxis and adherence

Investigations:
Baseline: CD4 count (%), X-ray chest, WBC, Hb% and ALT 6-Monthly: CD4 count (%), WBC and Hb%
Paediatric First line ART: Initiation

ART in Adults and Children

Similar pathogenesis of HIV infection General virological and immunologic principles for antiretroviral therapy

Unique considerations in infants, children and adolescents

Paediatric First line ART: Initiation

Special Considerations in Paediatric ART

Diagnostic issues

Pharmacokinetic issues
Availability of paediatric formulations Age-related differences in virological and immunologic markers Adherence issues

Paediatric First line ART: Initiation

Changing Pharmacokinetics
Age-related differences between children and adults
Body composition Renal excretion Liver metabolism Gastrointestinal function

Enzyme maturation

Paediatric First line ART: Initiation

Goals of ART
Use combination ARV therapy with at least 3 drugs
Slows disease progression Improves survival and quality of life Sustains virologic response better Normalises immune function

Delays development of resistance

Paediatric First line ART: Initiation

When to Start ART?

The decision-making process relies on Clinical and / or Immunological assessment

Paediatric First line ART: Initiation

Other Factors Influencing Initiation of ART

Evaluation of the social environment of the child
Caregivers understand ARV therapy, possible side effects, limitations, adherence schedule, etc Caregiver is ready for treatment adherence Caregiver is actively involved in the care of the child Family and / or social support available

Availability of paediatric formulations

Consistent drug supply
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When to Start ART?

Starting ARV therapy for the individual child is rarely an emergency! Management of life-threatening opportunistic infections can be an emergency

Treat opportunistic infections before starting ART

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Case study
Pooja is 2 years and 3 months old

She is HIV seropositive

In the last 6 months she has been suffering from 2 episodes of pneumonia, requiring hospitalisation She also has persistent oral thrush She has achieved normal developmental milestones, but has failed to gain weight and height as expected
Case-details continued in next slide
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Case study
O/E:

wt 8kg
Ht 75 cm Cervical lymphadenopathy Hepatosplenomegaly Her CD4 count is 500/cmm

Should she be started on ART?

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Clinical and Immunological Criteria for starting ART in Infants (<24 Months)
All infants and young children under 24 months of age with confirmed HIV infection should be started on ART, irrespective of clinical or immunological stage
Where virological testing is not available, infants and young children under 18 months of age with clinically diagnosed presumptive severe HIV should be started on antiretroviral therapy
Presumptive diagnosis of severe HIV disease: 2 or more of following:

Oral thrush Severe pneumonia Severe sepsis

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Clinical and Immunological Criteria for starting ART in Children (>24 Months)
Children >24 Months-upto age of 5 years: HIV-infected children >24 months according to clinical and CD4% criteria Clinical status:
Initiate ART for all clinical stage 3 and 4, irrespective of CD4 count or percentage

In children with TB, LIP, OHL, thrombocytopenia (stage 3): Use CD4 to guide ART initiation

Children >5 years of age: Follow CD4 count as in Adult ART Guidelines
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Paediatric First line ART: Initiation

CD4 Criteria of Severe HIV Immunodeficiency

Immunological Age-specific recommendation to initiate ART 24 months35 months 36 months59 months 5 years

Marker

CD4 % CD4 count

20%
750 cells/mm3

15%
350 cells/mm3 Follow Adult ART Guidelines

ART should be initiated by these cut-off levels, regardless of clinical stage; a drop of CD4 below these levels significantly increases the risk of disease progression and mortality CD4% is preferred for children <5 years
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Paediatric First line ART: Initiation

Formula for calculating CD4% when CD4 absolute count is available

% CD4 Count =
Absolute CD4 T-Lymphocyte Count Total lymphocyte count
Absolute CD4 +T-lymphocyte count: As obtained by the flowcytometer

X 100

Total lymphocyte count (TLC) can be obtained by a cell counter or alternatively obtained using the following formula:

TLC =

Total no. of lymphocytes (DC) x Total leucocytes count 100

Total leucocyte count can be obtained either through a counting chamber or using a haematology analyser with the blood sample drawn at the same time as CD4 sample
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What to Start? First line Antiretroviral Drugs

Nucleoside reverse transcriptase inhibitor
Zidovudine (AZT) Stavudine (d4T) Lamivudine (3TC)

Non-nucleoside reverse transcriptase inhibitor

Nevirapine (NVP) Efavirenz (EFV)
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Paediatric First line ART Regimens

Paediatric Regimen Regimen P I Regimen P I (a)

Regimen
Zidovudine + Lamivudine + Nevirapine
Stavudine + Lamivudine + Nevirapine Zidovudine + Lamivudine + Efavirenz

Remarks
Preferred paediatric regimen for children with Hb >9 g/dL For children with Hb <9 g/dL preferred for children on anti-TB treatment; Hb >9 g/dL and age >3 yr and weight >10 kg for children on anti-TB treatment tuberculosis treatment; Hb <9 g/dL and age > 3 yr and weight >10 kg

Regimen P II

Regimen P II (a) 1. 2.

Stavudine + Lamivudine + Efavirenz

Efavirenz is the preferred drug over Nevirapine, whenever children are being treated with Rifampicin containing drug regimen for TB co infection However, in Children aged <3 years and in children weighing <10 Kg, Efavirenz is contraindicated
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Paediatric First line ART: Initiation

Case study (Contd.)

Pooja, has to be started on ART on the basis of her clinical staging of the disease (WHOstage 3) and immunologic staging (severe).

What are the baseline investigations to be done before starting ART ?

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Base line Investigations

Hb, WBC

X-ray Chest
LFT RFT Blood sugar It was found that Pooja had a Hb of 7g/dL

What should be the preferred ART prescribed to her?

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Case study (Contd.)

Zidovudine 1st choice in non-anaemic children (Hb >9 g/dL) Stavudine 1st choice in those who are anaemic (Hb <9 g/dL)

Thus here Pooja can be started on Stavudine + Lamivudine + Nevirapine (Regimen P I (a): d4T + 3TC + NVP)

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ART in CLHIV with TB co infection

Arun is a 6 year old HIV infected boy, who presented with the symptoms of cough and low grade fever for last 1 month. His father was recently detected to have pulmonary TB. After thorough clinical examination and investigations, Arun was diagnosed to be suffering from pulmonary TB and put on Category I ATT. His CD4 count was 195/l.

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ART in CLHIV with TB co infection

Does he need to be started with ART immediately? If and when ART is started, what drugs should be used?

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ART in CLHIV with TB co infection

Type of TB Eligible Timing of ART in relation Clinical Staging to start of TB treatment and CD4 Counts Start ART irrespective of any clinical stage and irrespective of any CD4 count Start ATT first (Category I or II) Start ART as soon as TB treatment is tolerated (after 2 weeks & before 2 months) ART Recommendations

Pulmonary TB (Clinical Stage III)

Extra pulmonary TB (Clinical Stage IV) 1. 2.

Start Efavirenz containing ART Regimen (Regimen II or Regimen II a)

Efavirenz is the preferred drug over Nevirapine, whenever children are being treated with Rifampicin containing drug regimen for TB co infection However, in Children aged <3 years and in children weighing <10 KG, Efavirenz is contraindicated
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Paediatric First line ART: Initiation

ART in CLHIV with TB co infection

Age Group / Body weight ART regimen
P II: Zidovudine + Lamivudine + Efavirenz

Age 3 years Body weight: >10 kg

Preferred for children with Hb >9 g/dL and bodyweight >10 kg

P II a: Stavudine + Lamivudine + Efavirenz

Preferred for children with Hb <9 g/dL and bodyweight >10 kg

Age <3 years Body weight: <10 kg

2 NRTIs + Abacavir (3 NRTIs)

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ARV drug Formulations available for CLHIV in ART Centres

Drug Regimen Preparation Drugs
d4T6+3TC (disp.tab) d4T6+3TC+NVP (disp.tab) AZT60+3TC30 AZT60+3TC30+NVP50 EFV 200 mg (Tab) EFV 50 mg (tab) NVP Syrup (50mg/5ml) AZT/3TC (Adult) d4T30/3TC (Adult) AZT/3TC/NVP (Adult) d4T30/3TC/NVP (Adult) ABC60+3TC30 DDI 125 DDI 200 LPV/ r 125 LPV/ r syrup Prescribed according to weight band Drugs used in First line ART Adult preparations prescribed according to weight band Prescribed according to weight band

Drugs used in Second line ART and alternate first line ART

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Components of Follow-up Visits

Counsel the patient / caregiver

Adherence monitoring
Evaluate efficacy of treatment

Monitor for Adverse Events (AE)

Detect Opportunistic infections (OIs), if any Diagnose Immune reconstitution inflammatory syndrome (IRIS)

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Follow-up Visits: Clinical Evaluation

Monitoring of Growth Weight / Length or Height / Head Circumference Assessment of Neurodevelopment Clinical Evaluation for:

Detecting Adverse Effects of ARVs

Diagnosing Opportunistic Infections Determining efficacy of therapy Fill up Follow up details in the white card
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Monitoring & Follow up of ART

Monitoring tool
Clinical & Adherence Counselling Hb. Yes

DAY 0 Baseline

15th DAY

1ST Month

2ND Month

3RD Month

6TH Month

Each and Every Visit

Yes (if on AZT)

Yes (if on NVP)

Yes (if on AZT)

Yes (if on NVP)

Yes

Yes

ALT

Yes

Yes*

Yes*

CD4 Count

Yes

Yes

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Clinical improvement
Yes Continue ART

No

Immunological improvement No Good Adherence

Yes

Yes

Continue ART

No

Repeat Adherence counselling Re-enforce treatment support

Evaluating a child on ART at follow-up visit

Good Nutritional support Yes Check for new clinical events

No
Repeat Adherence counselling Re-enforce treatment support

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Evaluating response to ART in a child with no clinical and immunological improvement at follow up visit
New Clinical Event

No

Continue ART

Yes
Check for other causes

New OI

IRIS

ARV Related Toxicity Drug interaction

Treatment failure

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Key Points
All the HIV infected infants and young children (<2 years) have to be initiated on ART, irrespective of clinical staging & CD4% Recommendations for ART in children (aged >2years) based on clinical and age-based CD4% or absolute CD4 count criteria First line regimens in India is based on 3-drug combinations (Zidovudine or Stavudine + Lamivudine + Nevirapine or Efavirenz) Both the child and the caregiver should have been counselled before initiating ART
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