Transcript 03.04 Paediatric HIV

Module 3
Unit 4: HIV and ART in Children
OBJECTIVES
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Describe the epidemiology and natural history of
HIV in infants and children
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Describe how to diagnose paediatric HIV infection
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Describe the staging of paediatric HIV infection
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Discuss the use of ART in pediatric population
including:
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When to start treatment
When to stop treatment
Monitoring therapy
Adherence and support
Epidemiology
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1 million live births in Kenya annually
10% born to HIV infected mothers
Without PMTCT 30% of these become
infected
About 20,000 neonates acquire HIV annually
About 10,000 (50%) die within first 2 years
HIV has made a huge impact on infant
mortality
Epidemiology - Transmission
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> 90% pediatric HIV infection acquired from
HIV positive mothers through vertical
transmission and breast feeding. (Mother to
child transmission –MTCT)
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Transmission occurs in 25-30% infants born to
mothers with HIV infection
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5%
10-20%
10-20%
- intrauterine
- during delivery
- breastfeeding
Epidemiology - Transmission
Factors facilitating MTCT
 Maternal disease status
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High viral load/low CD4 count
Maternal acquisition of HIV in pregnancy or
lactation
Vaginal infections, chorioamnionitis
Epidemiology - Transmission
Factors facilitating MTCT
 Labor
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Prematurity
Prolonged/difficult
Duration of membrane rupture
>4hours/PROM
Invasive monitoring and procedures
Epidemiology - Transmission
Factors facilitating MTCT
 Infant feeding
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Prolonged breast feeding
Breast health – sore nipples/abscesses/mastitis
Mixed feeding. Exclusive BF for 3-6 months results
in no excess transmission compared to formula
feeding alone
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Exclusive BF = BF only without additional fluids, water,
food, teats or pacifiers AND no demand feeding
Oral thrush in breast fed infant
Epidemiology - Transmission
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Other routes of transmission
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Contaminated needles and instruments
Transfusion of blood and blood products
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Hemophiliacs
Sicklers
Sexual
Natural History Of HIV Infection
Natural History
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Viral transmission
Acute retroviral syndrome
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Seroconversion with recovery
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Continuing CD4 loss depends on plasma viral load
Symptomatic HIV infection/AIDS
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Development of immunity
Rapid decline in viremia and slowing down of CD4 cell loss
Asymptomatic chronic HIV infection
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High plasma viremia and rapid CD4 decline
Increasing viremia
Rate of CD4 decline increases
Death
NATURAL HISTORY
In uninfected children
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Absolute CD4 counts
high in young children
Decline to adult levels
by 6 yrs
CD4% does not change
much with age
6000
4000
5th percentile
95th percentile
2000
0
0 4 9 12
24
60
Age in Months
Age-related Decrease in CD4+
Percentage
80
CD4+ %
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CD+ Number/mm3
Age-related Decrease in CD4+ Number
60
5th percentile
95th percentile
40
20
0
0
4 9 12
24
Age in Months
60
Natural History
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In HIV infected children
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Infants < 12 months with very high viral loads (>100,000) may be at
high risk for disease progression and death
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Low viral loads at birth rise to several million copies within the first 1-2
months of life
Very slow decline over several years to reach “set point”
Predictive value of VL not good in young infants
Much overlap with rapid and non-rapid progressors
Evaluate CD4+ counts and percentages as well
Very high HIV RNA levels may be correlated with disease progression
and death.
NATURAL HISTORY – Two commonly
seen patterns of progression
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Slow Progressors
 Low viral loads at birth
 Stable CD4 counts for
2-10 years
 Growth stunting, skin
problems and recurrent
bacterial infections
common
 Opportunistic infections,
AIDS related conditions
with progressive
immunosuppression
 Encephalopathy rare
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Rapid Progressors
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High viral load at birth
Rapidly declining CD4
Low Birth Weight
Chronically unwell
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Persistent or recurrent
diarrhea
Recurrent bacterial and
fungal infections
Severe encephalopathy
before 18 months
Clinical Presentation
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Failure to thrive
(FTT), wasting
syndrome
Developmental delay
or regression
Recurrent bacterial
infections
TB
Chronic fever and
diarrhea
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Infective and noninfective dermatoses
hair changes
Generalized
lymphadenopathy,
hepato-splenomegally
Parotid enlargement
Unexplained organ
disease affecting the
heart, kidney, liver,
brain and bone marrow
(hematological)
World Health Organization
Clinical Staging for Pediatric HIV
Stage I (mild)
 Asymptomatic, or persistent generalized LN
Stage II (moderate)
 Unexplained, chronic diarrhea (> 1 month)
 Severe, persistent, or recurrent candidiasis outside
the neonatal period
 Weight loss or FTT
 Persistent fever (> 1 month)
 Recurrent severe bacterial infections
WHO Clinical Staging
Stage III (severe)
 AIDS defining OI (PCP, TB, Crypto, CMV etc)
 Wasting syndrome (severe FTT)
 Progressive encephalopathy
 Malignancy
 Recurrent septicemia or meningitis
CDC Classification (staging) of
Pediatric HIV Infection
Category Disease
N
Not symptomatic (or only One category A condition)
A
Mildly symptomatic with 2 or more of following:
Lymphadenopathy
Hepatomegaly
Splenomegaly
Dermatitis
Parotitis
Recurrent or persistent URTI, sinusitis or otitis media
Category Disease
(CDC)
B
Moderately symptomatic
Diarrhoea, recurrent or chronic
Bacterial infection – pneumonia, meningitis, sepsis (1 episode)
Fungal infection - Oropharyngeal candidiasis
Viral infection – CMV, Herpes simplex (stomatitis, bronchitis,
pneumonitis, esophagitis), Herpes zoster, disseminated Varicella
Other OI – Toxoplasma before 1 month, Nocardiosis
Major organ dx – Cardiomyopathy, nephropathy, hepatitis.
Persistent fever > 1 month
Lymphoid interstitial pneumonia
C
Severely symptomatic – AIDS defining conditions
HIV wasting disease
Esophageal candidiasis
Disseminated or extrapulmonary tuberculosis
HIV encephalopathy
Cryptococcal meningitis, Cryptosporidiosis
Lymphomas, Kaposis sarcoma
Clinical
category
Diagnosis
(CDC)
C
(Continued)
Severely symptomatic:
Multiple recurrent severe bacterial infection
Esophageal or pulmonary candiadiasis
Disseminated coccidioidomycosis
Extra pulmonary cryptococcosis
Cryptosporidiosis or isosporiasis
CMV infection > 1 month of age
Disseminated histoplasmosis
Kaposi’s sarcoma
Primary lymphoma of the brain
Burkitt’s or immunoblastic lymphoma
Disseminated or extrapulmonary tuberculosis
Disseminated other or unspecified mycobacteria sp.
Disseminated Mycobacteria avium
Pneumocystis carinnii pneumonia
Herpes simplex virus infection > 1 month of age
Progressive multi focal leucoencephalopathy
Recurrent salmonella (nontyphoidal) septicemia
Toxoplasma of the brain (> 1 month of age)
Wasting syndrome
IMMUNOLOGIC STAGING
Immune
category
Category 1:
Not
immunosuppressed
Category 2:
Moderately
immunosuppressed
Category 3:
Severely
immunosuppressed
< 12 months
1-5 years
6-12 years
CD4 counts
CD4
percentage
CD4 counts
CD4
percentage
CD4 counts
CD4
percentage
> 1500
> 25%
> 1000
> 25%
> 500
> 25%
750-1,499
15-24%
500-999
15-24%
200-499
15-24%
< 750
< 15%
< 500
< 15%
< 200
< 15%
CDC - Pediatric HIV Staging
Stage N1 – Asymptomatic, not
immunosuppressed (early disease)
Stage A2 – Mildly symptomatic,
moderately immunosuppressed
Stage C3 – Severely symptomatic,
Severely immunosuppressed (AIDS,
Acquired immunodeficiency syndrome)
Diagnosis
Before age 18 months
(Maternal antibodies cause positive results in all infants
born to HIV positive mothers)
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Need to identify virus – usually not possible
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HIV DNA PCR
HIV RNA PCR
P24 antigen- variable sensitivity
Not BF: test at age 1 month repeat 3 months later
BF: wait until 3 months after cessation of BF to confirm final
HIV status.
Clinical diagnosis
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Mother HIV positive + WHO III + CD4<15
Diagnosis
After 18 months:
 HIV ELISA antibody test
 By 18 months, maternal antibodies
have cleared
DIAGNOSIS - summary
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In infants HIV is diagnosed by 2 positive
virological tests performed on blood samples
taken on 2 separate dates.
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HIV is excluded by 2 or more negative virological tests
at >age 1 month, one of which is performed at age >4
months in a non-breastfed infant
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If BF wait 3 months after cessation of BF
Antibody tests: 2 or more antibody tests after 18
months confirm or exclude diagnosis.
Antiretroviral Treatment
General Concepts
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Early recognition and diagnosis of complications
results in early treatment and better outcomes for
patients
Knowledgeable providers assist in prevention and
recognition of complications
Timely intervention with ART results in better
clinical outcomes
ARV prescription requires careful assessment and
preparation, followed by consistent support
ART General Concepts
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Ongoing HIV replication leads to immune system
damage
Timely ART, before onset of severe
immunosuppression results in better clinical
outcomes
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ARV prescription requires careful assessment and
preparation, followed by consistent support
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Adherence to treatment is essential in order to
achieve intended goals
Pretreatment Assessment
Goals:
 Determine if patient needs treatment
 Ensure safety of ART
 Rule out underlying problems that may
impact on treatment
 Treat any active OI’s
 Prepare patient for treatment
Pretreatment Assessment
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Clinical and laboratory assessment
Preparation of patient should include
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Assessment as to whether patient ready and able to start and
continue long term treatment
 Home environment, lifestyle, social and financial situation
 Proximity to treatment centre and any local health care
networks
 Parental and child readiness
 Availability and suitability of formulations
 Cost and affordability
 Psychosocial and family support
 Disclosure
 Adherence assessment
Pretreatment Assessment
Information to ensure patient adherence:
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Need lifelong treatment even when they may feel well
Expected benefits
Potential side effects of (proposed) treatment
Necessity for regular follow up to monitor progress and
toxicity
Adherence and relation to outcome
Drug resistance and consequences
Adjusting to changes in living pattern
Medication not to be shared
Point of contact if needed
CONSIDERATIONS
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Stage of development
Dosing frequency
Side effects
Co-infections
Meal requirements
Storage requirements
Never…
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Never prescribe ARV’s in absence of
adherence counselling and support
Never prescribe mono or dual therapy
for treatment of HIV infection
If ARV’s are to be discontinued, stop all
drugs as instructed
Never change a prescription unless it is
absolutely necessary.
OTHER CONSIDERATIONS
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Cautions when ART considered in patients
with:
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Severe anaemia < 6.9gm/dl
Severe thrombocytopaenia
Severe neutropaenia
Renal insufficiency
Hepatic insufficiency
History of prior ARV use
Current anti-TB medications
ARV Drugs
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Special considerations in children
 Children >3yrs may take tabs/caps
formulation
 Some caps may be opened and mixed with
food/drink for even younger children
 Chewable tablets may be crushed and
mixed with food or drink
When to Start: < 18 months
PCR available and positive
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WHO Stage I or II – CD4%<20%
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WHO Stage III – regardless of CD4
When to Start: < 18 months
PCR unavailable, CD4 available
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Start if CD4<20% plus clinical stage III
In absence of CD4/PCR
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Continue Cotrimoxazole prophylaxis
Wait till 18 months when antibody test can be used
When to Start: >18 months
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WHO stage III/CDC stage C
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Regardless of CD4
WHO Stage I or II - CD4 <15%
Absolute CD4 count <200
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In children over 6 years
(CD4 counts similar to adults at this age)
INITIAL REGIMENS
Stavudine
+
Lamivudine
+
Nevirapine
or
Zidovudine
+
Lamivudine
+
Nevirapine
NB: Stavudine syrup is unstable at room temperature. If
a liquid needs to be used, and no refrigeration at home,
use AZT
When to Stop/Change
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Toxicity – replace offending agent with equivalent drug
Failure
 Immunological
 CD4 decline > 5 percentile points
 Rapid decline in CD4 count – >1/3 in less than 6 months
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Virological (Usually unavailable)
 Failure to suppress viral load at 8-12 weeks by at least 5 fold
 Failure to achieve below assay detection limit by 24 weeks
 Increase in VL from previously suppressed level (by at least
3-5 fold)
Clinical deterioration (progression in the clinical stage)
Other – new treatment/formulations; patient/parent reasons
Toxicity
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Hb < 7gm/dl
Platelets < 49,000
Neutrophils < 250
Bilirubin 3-7x upper normal
SGPT 10x upper normal
Amylase, lipase: 2-3x upper normal
2nd LINE REGIMES
If 1st line is
AZT+3TC+NVP
If 1st line is
d4T+3TC+NVP
Change to:
Change to:
d4T+ddI+LPV/r
Or
d4T+ddI+NFV
AZT+ ddI+ LPV/r
Or
AZT + ddI+NFV
WHY REGIMENS CAN FAIL
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Poor Adherence
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Consider who administers
How drug is administered
Is drug appropriate, taste, vomiting, food
Resistance:
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One or 2 drug resistance mutations exist at baseline by
chance
3 or more drugs are needed to provide adequate
genetic barrier to resistance
Sub-therapeutic levels provide selective pressure for
resistance
Within days, resistance develops to NVP, EFV, 3TC if
not taken appropriately
CLINICAL FAILURE
- Progressive neurodevelopmental
deterioration
- Growth failure despite
adequate nutritional
support and with no other
explanation
- Disease progression
(advance to another
clinical category)
WHEN TO STOP
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Life threatening side effects or adverse
reactions
Poor compliance
MONITORING required
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Clinical
Laboratory
Treatment adherence
Appointment adherence
MONITORING-check list
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Initial ARV visit: family education
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Review understanding of HIV disease
progression, adherence
Request demonstration of accurate dosing
and medication administration
Return visit in a week
Interval history, physical examinations
including weight and growth
Laboratory Monitoring
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CD4 every 6 months (earlier if
indicated)
FBC, SGPT/ALT 3 monthly or as
appropriate
Others as appropriate for toxicity or
inter-current illnesses
Adherence Issues to Consider
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Children depend upon adults to administer drugs
Adherence may be affected by stage of
development (spitting, vomiting, running away)
Providers need to teach families techniques of
giving medicine to young children
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Use of syringe for measurement and administration
Crushing of meds
Mixing in fruit juice, other foods
Opening of capsules
Repeat dose if vomited