Paediatric HIV

1
Paediatric HIV

• Dr. Russell Pierre
• Senior Lecturer, Consultant Paediatrician
• University of the West Indies

MOH 3rd Annual HIV Clinical Management ARV
Therapy Training Workshop 29-31 March 2006
2
Objectives

• At the end of this presentation participants
  should be able to
• Understand the pathogenesis of HIV in infants and
  children
• Recognise common presenting features of
  paediatric HIV
• Understand the strategies for management of
  HIV-affected infants and children
• Appreciate the application of paediatric HIV/AIDS
  management in the Jamaican context

3
Philosophy

• Life-cycle / developmental approach to issues of
  diagnosis and treatment
• Public-health approach to management
• Prevention of HIV
• Prevention of acute illnesses / opportunistic
  infections
• Preservation of immune function
• Improving quality of life
• Palliative care issues

4
Historical perspective

• Paediatric HIV first recognised in 1986 in
  Jamaica
• Pioneers who initiated individual pockets of
  paediatric HIV care
• 2002 Development of Pediatric Infectious
  Diseases Clinics in Greater Kingston region
  coordinated by Prof CDC Christie the
  implementation of the Kingston Pediatric
  Perinatal Program
• Overall Aim Reduce MTCT
• Improve survival QOL of infected children
  and adolescents
• 2003 Program received a major boost in
  therapeutic and laboratory support through
  Clinton HIV/AIDS Initiative and Global Fund
• 2003-present Established clinics in St. Anns
  Bay, Cornwall Regional, Mandeville, and MayPen
  Hospitals through outreach and preceptorship
  training

5
JAMAICA Pediatric AIDS Cases Deaths (1982 -
2004)
Source Ministry of Health, Jamaica
6
Historical perspective

• Dramatic fall in incidence of new cases of
  paediatric infections in US
• Paediatric ARV History
• 1988 monotherapy with AZT
• 1994 dual therapy
• 1998 triple therapy with HAART

7
Key differences from infected adults

• Perinatal transmission
• Effect of virus on immature immune system
• Virologic response
• CD4 response reliance on CD4 to determine
  severity of immunologic deterioration
• Clinical presentation
• Diagnostic challenge in lt 18 months

8
Possible routes of transmission
In-utero
At Birth
During breastfeeding
9
Other modes of transmission

• Sexual abuse, exploitation, experimentation,
  consensual
• Transfusion (rare in Ja)
• Intravenous drug use (rare in Ja)

10
Natural history of paediatric HIV

• Newborns most studies generally well at birth
• Virologic response increases rapidly in initial
  2-3 months then slowly declines to virologic
  set-point after several months to years
• Immunologic response brisk and variable T cell
  proliferation hence cannot rely on absolute CD4
  as marker of immune deficiency CD4 percent lt15
  indicative of severe immune deficiency

Virologic set-point state of in-vivo equilibrium
between viral production and elimination
11
Virologic response
Child Adult
Time (years)
Infection
12
Natural history of paediatric HIV
Pattern of Clinical Progression
Asymptomatic
Mild to Moderate
Severe
13
Natural history of paediatric HIV

• Patterns of Progression

Rapid 20
Intermediate 70
Slow 10
14
Rapid Progressors

• PCP
• FTT
• CNS invovlement
• Chronic GE
• Recurrent infections
• CMV infection
• Persistent candidiasis

15
Progression to AIDS

• Early onset perinatal infections in infants lt
  12 months
• Commonest manifestations
• recurrent pneumonia
• recurrent diarrhoea
• growth failure
• neurological abnormalities

16
Slow Progressors

• Generally well until late childhood
• Some completely asymptomatic
• Few---progress to AIDS
• Main problems pneumonia / Lymphocytic
  interstitial pneumonitis (LIP), stunting

17
Clinical manifestations
18
Generalised, persistent lymphadenopathy
19
Dermatitis
20
Mucocutaneous Candidiasis
21
Recurrent lower respiratory tract infections

• Bacterial pneumonia
• Community acquired infections
• Need to always consider tuberculosis
• Increased occurrence of LRTI associated with LIP

22
Pneumocystis jiroveci pneumonia (PCP)
23
Lymphocytic Interstitial Pneumonitis
24
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25
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26
Chronic lung disease
27
Wasting / FTT / Malnutrition
28
Hepatosplenomegaly
29
Neurodevelopmental abnormalities

• Developmental delay
• Developmental regression
• Spasticity, hyperreflexia
• Impaired cognitive function
• CT scan brain generalized cortical atrophy with
  ventricular enlargement and calcified basal
  ganglia (arrow)
• (Ref. D. Carli C et al, Ann Neurol 34(2)
  198-205, 1993.)

30
Clinical manifestations

• Recurrent or persistent upper respiratory tract
  infection, sinusitus or otitis media
• Parotitis
• Recurrent diarrhoea
• Bacterial sepsis
• Organ-specific dysfunction

• CDC. 1994 Revised classification system for
  human immunodeficiency virus infection in
  children less than 13 years of age. MMWR, 1994.
  43 (No. RR-12) p. 1-10

31
Reducing the impact of HIV on children
32
AIM Increase survival Improve quality of life
33
Give a child a chance

• Early Intervention is the key

34
Framework for a comprehensive approach to manage
HIV in infants children
Prevent unintended pregnancy in HIV women
Prevent MTCT
Prevent HIV in women
Provide accessible treatment, care and support
for HIV-infected women, their infants and
families
35
Key aspects of management

• Prevention of HIV infection
• Early diagnosis
• Early detection high index of suspicion
• Prevention ( timely treatment) of common
  childhood illnesses
• Prevention and early treatment of opportunistic
  infections
• HAART preserve / restore immune system
• Palliative care
• Multidisciplinary management approach

36
Management of HIV-exposed infant

• ARV prophylaxis (pre- and post-exposure)
• Breastfeeding alternatives
• Follow-up and monitoring
• PCP prophylaxis Cotrimoxazole
• Diagnosis of HIV infection
• Immunizations National EPI recommendations
• Nutrition
• Growth development
• Clinical evaluation for stigmata of HIV infection
• Challenges follow-up, adherence to prophylaxis,
  stigma of non-breastfeeding

37
Diagnosis of HIV infection in exposed infant

• Serial qualitative DNA PCR is currently the
  accepted standard for early diagnosis
• DNA-PCR 2 consecutive readings
• 1-2 months
• 3-6 months
• Antibodies (Elisa)
• 12 months in non-breastfed infant
• Others RNA PCR, p24, viral culture
• Passive transfer of maternal Ig G leads to
  detectable antibody in uninfected children for up
  to 18 months
• Antibody tests e.g.ELISA not diagnostic until 18
  months unless negative

38

• Lancet 2004 364 1865-71

39
Diagnosis of HIV infection in child

• HIV Elisa with confirmatory Western blot
• gt 18 months of age

40
Classification of paediatric HIV/AIDS

• CDC Clinical Category
• N asymptomatic
• A mildly symptomatic
• B moderately symptomatic
• C severely symptomatic AIDS defining
  conditions

CDC 1994 Revised classification system for human
immunodeficiency virus infection in children less
than 13 years of age. MMWR, 1994. 43 (No. RR-12)
p. 1-10
41
Classification of paediatric HIV/AIDS

• CDC Immune Category
• CD4, and age-specific CD4 count
• 1 ? 25 none/mild suppression
• 2 15 24 moderate suppression
• 3 lt 15 severe suppression

42
Classification of paediatric HIV/AIDS

• WHO Staging System
• Clinical Stage 1 (asymptomatic)
• Clinical Stage 11 (mild to moderate)
• Chronic diarrhoea
• Candidiasis
• FTT
• Persistent fever
• Recurrent severe bacterial infections
• Clinical Stage 111(severely symptomatic)
• AIDS defining conditions
• Severe FTT
• Progressive encephalopathy
• Malignancy
• Recurrent sepsis

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Comprehensive management of HIV-infected child

• Multidisciplinary management approach
• Prevention ( timely treatment) of common
  childhood illnesses
• Regular ambulatory care
• Growth development monitoring
• Immunizations National EPI guidelines
  influenza, pneumococcal
• Nutrition food safety

44
Comprehensive management of HIV-infected child

• Prevention and early treatment of opportunistic
  infections
• Cotrimoxazole
• Fluconazole
• Azithromycin
• Aciclovir
• Isoniazid
• IVIG
• Palliative care

45
Antiretroviral Therapy
Preserve and restore immune system
46
Who, when, what, how???

• Several guidelines Caribbean, Jamaican, WHO,
  DHHS..
• Bottom-line issues for consideration

• Feasible
• Accessible
• Affordable
• Safe
• Sustainable
• Practical

47
Practical guidelines

• Any HIV-infected infant or child with AIDS
  defining condition or severe immunosuppression
  (CD4 lt 15)
• All HIV-infected infants lt 12 months of age,
  regardless of clinical, immunologic or virologic
  parameters
• All others discuss and consider treatment
  according to guidelines

48
Practical considerations

• Limited range of paediatric formulations in
  Jamaica
• Initiation of therapy adherence in children is
  caregiver dependent
• Treatment options are limited
• Aim for practical, simplified regimes

49
Effectiveness of interventions in treating
Paediatric HIV/AIDS

• The Jamaican Experience

50
Collaborators

• Kingston Pediatric Perinatal HIV/AIDS Program
  (KPAIDS) Team
• University of the West Indies University
  Hospital of the West Indies
• Jamaica Ministry of Health Bustamante Hospital
  for Children, Comprehensive Health Centre,
  Spanish Town Hospital, National AIDS Program
• Elizabeth Glaser Pediatric AIDS Foundation
  (EGPAF), Pfizer Foundation

51
Aim

• To characterize the effectiveness of
  interventions in a cohort of HIV-infected
  children and adolescents attending Paediatric
  Infectious Diseases Clinics in Greater Kingston,
  Jamaica

52
Objectives

• Describe the demographic and clinical
  immunological profile of the cohort
• Determine enrollment pattern and uptake of
  Antiretroviral therapy (ART)
• Characterize outcomes related to
  hospitalisations, bacterial and opportunistic
  infections, growth, morbidity and mortality

53
Methods

• Longitudinal observational cohort study
• Paediatric Infectious Diseases Clinics at UHWI,
  BHC, CHC STH
• HIV-infected infants and children consecutively
  enrolled in KPAIDS Program
• Period 1 Sept. 2002 to 31 Aug. 2005
• HIV status confirmed by HIV DNA pcr, Elisa/WB
  where appropriate

54
Methods

• Training of healthcare personnel
• Development of unified protocols for clinical
  management
• Primarily ambulatory surveillance also
  in-patient consultations, case management
• Data tracking and audit morbidity, mortality,
  hospitalisations, laboratory markers
  (haematology, biochemistry, cultures, immunology,
  flow cytometry, viral load)
• Dbase management analysis-Excel, Access, SPSS,
  EpiInfo where indicated

55
Comprehensive Interventions

• Integrated multidisciplinary approach to
  ambulatory treatment care
• Increased access to care
• Inpatient consultations
• Immunisation, nutrition, growth/development
  surveillance
• MOH Jamaica guidelines

• Prophylaxis Opportunistic Infections bactrim,
  fluconazole, azithromycin, isoniazid,
  clotrimazole beclomethasone/ salbutamol MDI
• ARV counselling, treatment, adherence and AE
  monitoring
• High index of suspicion for TB

56
Results
57
Enrollment Profile
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Enrollment Pattern
59
Characteristics of Cohort
60
Clinical Immunological Profile
61
CDC Category Profile
62
Median CD4 percentage by year
CD4 percent
0.0
ANOVA F 1.015 p0.318
Year
63
ARV Uptake
64
ARV Uptake
65
ARV Uptake
Ever on ARV
Yes No
38
62
66
ARV Uptake
Regime 1
Zidovudine Lamivudine Nevirapine
85
6
6
2
1
67
ARV Uptake

• ARV-experienced group
• Regime 2 10.7
• Regime 3 5
• Regime 4 0.8
• Reasons for regime change toxicity/AE (13),
  clinical failure (8), financial limitations
  (3), optimisation (2)
• 80 (ARV-naïve) currently on initial regime

68
Adherence levels for children on ART
69
Factors affecting adherence

• Factors significantly associated with
  non-adherence
• Older age of child (r0.428,p0.001)
• Missing clinic appointments (r0.340, p0.018)
• Nausea (p0.003)

70
Adherence to ART

• Adherence to pediatric ART 87
• Adherence correlated with immune-reconstitution,
  measured by CD4 counts/percent
• Adherence in institutions better because of
  directly observed therapy (DOT)
• Main reasons for non-adherence in children on ART
  are caregiver-related
• Knowledge about ART excellent except development
  of resistance
• Predictors of non-adherence Older age of child,
  missing appointments, nausea

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Growth Outcome

• Weight, height, BMI values standardized to z
  scores (CDC 2000 growth chart)
• Baseline, 6, 12, 24 months since initiation of
  antiretroviral therapy

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Weight for Age
73
Weight for Height
74
BMI for Age
75
Height for Age
76
Hospitalisation Profile

• Median 1.0 (Range 0 to 20) hospital admissions
• IQR 0 3 admissions

77
Incidence Density
78
Deaths
A
79
Summary
2002
2005
2003
2004
80
Conclusions

• Improved survival of HIV-infected children and
  adolescents
• Improved their quality of life

81
Conclusions

• Developed an ambulatory surveillance model for
  Paediatric HIV/AIDS treatment care in a
  developing country
• Focused on a Public Health Approach
• Integrated with existing resources in Jamaica
• Fostered an excellent collaboration with Jamaica
  MOH National HIV/AIDS Program

82
Future Directions
83
Future Directions

• Reducing MTCT to lt 2
• Strengthening paediatric HIV/AIDS treatment
  care capacity in rest of Jamaica
• Palliative care issues
• Challenges
• Issue of viral resistance
• Limitations for treatment options
• Maturing cohort of infected adolescents
  transition to adult life
• Sustainability of treatment and laboratory
  monitoring

84
Acknowledgements

• MOH, National AIDS Program
• All participating and facilitating institutions
• KPAIDS Team
• Children and their caregivers