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Transcript of Paediatric HIV
![Page 1: Paediatric HIV](https://reader030.fdocument.pub/reader030/viewer/2022032708/56812aaa550346895d8e6f8b/html5/thumbnails/1.jpg)
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
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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
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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
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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
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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
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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
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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
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Possible routes of transmission
In-utero At Birth During breastfeeding
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Other modes of transmission
• Sexual – abuse, exploitation, experimentation, consensual
• Transfusion (rare in Ja)
• Intravenous drug use (rare in Ja)
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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
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Time (years)
Vir
olo
gic
res
po
nse
Child
Adult
Infection
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Natural history of paediatric HIV
Asymptomatic Mild to Moderate
Severe
Pattern of Clinical Progression
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Natural history of paediatric HIV
Patterns of Progression
Rapid
20 %
Intermediate
70 %
Slow
10 %
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Rapid Progressors
• PCP• FTT• CNS invovlement• Chronic GE• Recurrent infections• CMV infection• Persistent candidiasis
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Progression to AIDS
Early onset – perinatal infections in infants < 12 months
Commonest manifestations:
• recurrent pneumonia• recurrent diarrhoea• growth failure• neurological abnormalities
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Slow Progressors
• Generally well until late childhood
• Some completely asymptomatic
• Few---progress to AIDS
• Main problems : pneumonia / Lymphocytic interstitial pneumonitis (LIP), stunting
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Clinical manifestations
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Generalised, persistent lymphadenopathy
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Dermatitis
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Mucocutaneous Candidiasis
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Recurrent lower respiratory tract infections
• Bacterial pneumonia• Community acquired
infections• Need to always
consider tuberculosis • Increased occurrence
of LRTI associated with LIP
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Pneumocystis jiroveci pneumonia (PCP)
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Lymphocytic Interstitial Pneumonitis
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Chronic lung disease
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Wasting / FTT / Malnutrition
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Hepatosplenomegaly
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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.)
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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
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Reducing the impact of HIV on children
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AIM
Increase survival
&
Improve quality of life
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Give a child a chance
Early Intervention is the key
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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
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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
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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
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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
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Lancet 2004; 364: 1865-71
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Diagnosis of HIV infection in child
HIV Elisa with confirmatory Western blot
[> 18 months of age]
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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
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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]
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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
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Comprehensive management of HIV-infected child
• Prevention and early treatment of opportunistic infections– Cotrimoxazole– Fluconazole– Azithromycin– Aciclovir– Isoniazid– IVIG
• Palliative care
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Antiretroviral Therapy
Preserve and restore immune system
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Who, when, what, how???
• Several guidelines: Caribbean, Jamaican, WHO, DHHS…………..
• Bottom-line issues for consideration
–Feasible–Accessible–Affordable–Safe–Sustainable
–Practical
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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
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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
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Effectiveness of interventions in treating
Paediatric HIV/AIDS
The Jamaican Experience
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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
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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
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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
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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
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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
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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
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Results
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‘ Actively’ Enrolled
~ 162
Total Enrolled196
Deaths
13
Transfer
7
Lost to Follow-up
12
Migration Overseas
2
Enrollment Profile
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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
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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
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Clinical & Immunological Profile
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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
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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
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ARV Uptake
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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
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ARV Uptake
yes
no
Ever on ARV
62%
38%
Ever on ARVYesNo
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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
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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
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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
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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)
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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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-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
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-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
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-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
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-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
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Hospitalisation Profile
Median 1.0 (Range 0 to 20) hospital admissions
IQR 0 – 3 admissions
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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
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Deaths
0
1
2
3
4
5
6
Frequency of Deaths
Year 1 Year 2 Year 3
Deaths by Cohort Year
Series1A
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Summary
Enrollment
Hospitalisation
Median CD4%
Deaths
2002 20052003 2004
ARV UptakeGrowth
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Conclusions
• Improved survival of HIV-infected children and adolescents
• Improved their quality of life
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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
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Future Directions
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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
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Acknowledgements
MOH, National AIDS Program
All participating and facilitating institutions
KPAIDS Team
Children and their caregivers