paediatric hiv
DESCRIPTION
Paediatric HIV. 衛生署 疾病管制局 中區傳染病防治醫療網 王任賢 指揮官. 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 - PowerPoint PPT PresentationTRANSCRIPT
Paediatric HIV
衛生署 疾病管制局中區傳染病防治醫療網
王任賢 指揮官
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
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
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 ProgramOverall 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. Ann’s Bay, Cornwall Regional, Mandeville, and MayPen Hospitals through outreach and preceptorship training
0
10
20
30
40
50
60
70
80
90
Nu
mb
er o
f C
ases
Cases
Deaths
Cases 1 1 4 10 7 9 12 12 30 27 49 44 55 70 83 66 81 67 61
Deaths 1 0 1 7 6 7 7 5 23 21 17 25 35 36 34 27 45 29 34
86 87 88 89 90 91 92 93 94 95 96 97 98 99 2000 2001 2002 2003 2004
JAMAICAPediatric AIDS Cases & Deaths (1982 - 2004)
Source: Ministry of Health, Jamaica
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
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 < 18 months
Possible routes of transmission
In-utero At Birth During breastfeeding
Other modes of transmission
• Sexual – abuse, exploitation, experimentation, consensual
• Transfusion (rare in Ja)
• Intravenous drug use (rare in Ja)
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 <15% indicative of severe immune deficiency
Virologic set-point: state of in-vivo equilibrium between viral production and elimination
Time (years)
Vir
olo
gic
res
po
nse
Child
Adult
Infection
Natural history of paediatric HIV
Asymptomatic Mild to Moderate
Severe
Pattern of Clinical Progression
Natural history of paediatric HIV
Patterns of Progression
Rapid
20 %
Intermediate
70 %
Slow
10 %
Rapid Progressors
• PCP• FTT• CNS invovlement• Chronic GE• Recurrent infections• CMV infection• Persistent candidiasis
Progression to AIDS
Early onset – perinatal infections in infants < 12 months
Commonest manifestations:
• recurrent pneumonia• recurrent diarrhoea• growth failure• neurological abnormalities
Slow Progressors
• Generally well until late childhood
• Some completely asymptomatic
• Few---progress to AIDS
• Main problems : pneumonia / Lymphocytic interstitial pneumonitis (LIP), stunting
Clinical manifestations
Generalised, persistent lymphadenopathy
Dermatitis
Mucocutaneous Candidiasis
Recurrent lower respiratory tract infections
• Bacterial pneumonia• Community acquired
infections• Need to always
consider tuberculosis • Increased occurrence
of LRTI associated with LIP
Pneumocystis jiroveci pneumonia (PCP)
Lymphocytic Interstitial Pneumonitis
Chronic lung disease
Wasting / FTT / Malnutrition
Hepatosplenomegaly
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.)
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
Reducing the impact of HIV on children
AIM
Increase survival
&
Improve quality of life
Give a child a chance
Early Intervention is the key
Framework for a comprehensive approach to
manage HIV in infants children
Prevent HIV
in women
Prevent unintended
pregnancy inHIV + women
PreventMTCT
Provide accessible treatment, care and support for HIV-infected women, their infants and families
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
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
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
Lancet 2004; 364: 1865-71
Diagnosis of HIV infection in child
HIV Elisa with confirmatory Western blot
[> 18 months of age]
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
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 – < 15% [severe suppression]
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
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
Comprehensive management of HIV-infected child
• Prevention and early treatment of opportunistic infections– Cotrimoxazole– Fluconazole– Azithromycin– Aciclovir– Isoniazid– IVIG
• Palliative care
Antiretroviral Therapy
Preserve and restore immune system
Who, when, what, how???
• Several guidelines: Caribbean, Jamaican, WHO, DHHS…………..
• Bottom-line issues for consideration
–Feasible–Accessible–Affordable–Safe–Sustainable
–Practical
Practical guidelines
• Any HIV-infected infant or child with AIDS defining condition or severe immunosuppression (CD4 < 15%)
• All HIV-infected infants < 12 months of age, regardless of clinical, immunologic or virologic parameters
• All others – discuss and consider treatment according to guidelines
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
Effectiveness of interventions in treating
Paediatric HIV/AIDS
The Jamaican Experience
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
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
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
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
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
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
Results
‘ Actively’ Enrolled
~ 162
Total Enrolled196
Deaths
13
Transfer
7
Lost to Follow-up
12
Migration Overseas
2
Enrollment Profile
Enrollment Pattern
0
5
10
15
20
25
30
35
40
45
Bef or e P r ogr am Y ear 1 Y ear 2 Y ear 3
Yearl
y E
nro
llm
en
t (%
)
Before Program
Year 3Year 2Year 1
GenderFemale
107 (54.6%) Male
89 (45.4%)
Age
At Enrollme
nt
Median 5.0 yr; Range <1 to 19.0 yr; IQR 2.2-8.1yr
Current Age
Median 6.0 yr; Range <1 to 20 yr; IQR 4.0-10.0 yr
Mode of transmission
MTCT 88.8%
Sexual 7.1%
Transfu-sion 1.5%
Unknown
2.5%
Clinic Site Population
UHWI 51.5%
BHC 32.6%
CHC 9.2%
STH 6.6%
Guardian StatusFamily Care151 (77%)
Institution Care45 (23%)
Characteristics of Cohort
Clinical & Immunological Profile
CDC Category Profile
CDC
N – asymptomatic
A – mild
B – moderate
C - severe
NA
BC
E nr ol lment
Last Visi t0
10
20
30
40
50
60
70
80
90
NA B
C
Enrollment
Last Visit
1995 2001 2002 2003 2004 2005
0.0
10.0
20.0
30.0
40.0
50.0
60.0
70.0
0.0
Year
CD
4
perc
en
t
ANOVA
F 1.015; p=0.318
CD4+
Median CD4+ percentage by year
ARV Uptake
0
10
20
30
40
50
60
70
80
90
100
Before Program Year 1 Year 2 Year 3
Cu
mu
lati
ve p
rop
ort
ion
on
A
RV
(%
)
Before Program
Year 2 Year 3Year 1
ARV Uptake
ARV Uptake
yes
no
Ever on ARV
62%
38%
Ever on ARVYesNo
AZT/3TC/NVPAZT/3TC/INDAZT/3TC/EFVAZT/3TC/D4TAZT/3TC/ABC
0
20
40
60
80
100
12085%
6%1%2%6%
ARV UptakeRegime 1
Zidovudine LamivudineNevirapine
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
Adherence levels for children on ART
1325.9
8774.1
100
0
20
40
60
80
100
120
Overall Family Care Residentialcare
Per
cen
tag
e o
f re
spo
nd
ents
(%
)
Adherent Non-adherent
Factors affecting adherence
Factors significantly associated with non-adherence:
1. Older age of child (r=0.428,p=0.001)
2. Missing clinic appointments (r=0.340, p=0.018)
3. Nausea (p=0.003)
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
Growth Outcome
• Weight, height, BMI values standardized to z scores (CDC 2000 growth chart)
• Baseline, 6, 12, 24 months since initiation of antiretroviral therapy
-2 -1.8 -1.6 -1.4 -1.2 -1 -0.8 -0.6 -0.4 -0.2 0
Baseline
6 mos
12 mos
24 mosWeight for Age Z- Score
[Median]
Weight for Age
-1.2 -1 -0.8 -0.6 -0.4 -0.2 0 0.2 0.4
Baseline
6 mos
12 mos
24 mosWeight for Height Z- Score
[Median]
Weight for Height
-1 -0.8 -0.6 -0.4 -0.2 0 0.2 0.4
Baseline
6 mos
12 mos
24 mosBMI for Age Z- Score
[Median]
BMI for Age
-1.8 -1.6 -1.4 -1.2 -1 -0.8 -0.6 -0.4 -0.2 0
Baseline
6 mos
12 mos
24 mosHeight for Age Z- Score
[Median]
Height for Age
Hospitalisation Profile
Median 1.0 (Range 0 to 20) hospital admissions
IQR 0 – 3 admissions
Event Incidence (per 100 patient months of follow-up)
No ARV On ARV
Hospitalizations 11.02 5.93
Pneumonia 4.71 2.49
Presumed PCP 0.58 0.05
Culture-positive sepsis
1.29 0.33
Tuberculosis 0.67 0.14
Toxoplasmosis CNS 0.13 0
CMV retinitis 0.04 0
Cryptosporidiosis 0.09 0
Cryptococcal meningitis
0.04 0
Urinary tract infection
1.29 0.96
Incidence Density
Deaths
0
1
2
3
4
5
6
Frequency of Deaths
Year 1 Year 2 Year 3
Deaths by Cohort Year
Series1A
Summary
Enrollment
Hospitalisation
Median CD4%
Deaths
2002 20052003 2004
ARV UptakeGrowth
Conclusions
• Improved survival of HIV-infected children and adolescents
• Improved their quality of life
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
Future Directions
Future Directions
• Reducing MTCT to < 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
Acknowledgements
MOH, National AIDS Program
All participating and facilitating institutions
KPAIDS Team
Children and their caregivers