Transcript Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection DR. S.K CHATURVEDI DR.

Guidelines for the Use of
Antiretroviral Agents in
Pediatric HIV Infection
DR. S.K CHATURVEDI
DR. KANUPRIYA CHATURVEDI
Antiretroviral (ARV) Therapy in
Adults and Children
•
Similar pathogenesis of HIV infection
•
General virologic and immunologic
principals for antiretroviral therapy
apply
•
Unique considerations in infants,
children, and adolescents
Special Considerations in
Pediatric ARV Therapy
•
Diagnostic issues
•
Pharmacokinetic changes
•
Availability of pediatric formulations
•
Natural history differences in virologic
and immunologic markers
•
Adherence issues
Changing Pharmacokinetics
•
Age-related differences between children &
adults
– Body composition
– Renal excretion
– Liver metabolism
– Gastrointestinal function
Lead to potential
differences in:
– Enzyme maturation
•
•
Drug distribution, metabolism and
clearance
Drug dosing and toxicities
Diagnostic Issues
•
Early identification = all pregnant women
must be offered HIV counseling and
testing
•
Perinatal infection = primary infection
•
Early diagnosis = starting therapy during
primary/early infection
Diagnostic Issues in Infants
•
HIV is diagnosed by 2 positive HIV virologic
tests performed on blood samples 2
separate dates
•
Use DNA PCR or HIV culture for diagnosing
at:
– Birth (<48 hours)
– 14 days (optimal)
– 1–2 months
– 3–6 months
Diagnostic Issues in Infants
•
HIV is reasonably excluded with:
– 2 or more negative virologic tests
• One at age >1 month
• One at age >4 months
– 2 or more negative HIV antibody tests at >6
months (in the absence of breast feeding)
Pediatric HIV Classification
Age-Specific CD4+ Immunologic Categories
Age of Child
Immune
Category
Category 1
Category 2
Category 3
<12 months
1–5 years
>6 years
Number/µL
(%)
Number/µL
(%)
Number/µL
(%)
>1,500
(>25%)
750–1,499
(15–24%)
>1,000
(>25%)
500–999
(15–24%)
>500
(>25%)
200–499
(15–24%)
<750
(<15%)
<500
(<15%)
<200
(<15%)
Pediatric HIV Classification
Clinical Categories
•
Category E: Perinatally Exposed
•
Category N: Not Symptomatic
•
Category A: Mildly Symptomatic
•
Category B: Moderately
Symptomatic
•
Category C: Severely Symptomatic
Immunologic Parameters in
Children
•
Absolute CD4+ counts in healthy children
are much higher than in adults
•
Normal absolute CD4+ counts slowly
decline to adult levels by age 6
•
If using CD4+ count for ARV decision,
use appropriate levels
•
CD4 percent varies less with age and
may be a better immunologic parameter
to follow in children <6 years
Immunologic Parameters in
Children
• Obtain baseline CD4 assays when child is
clinically stable
• Confirm CD4 changes with a second test
before making therapy decisions (when to
initiate therapy, when to change therapy, etc.)
HIV RNA and Children:
Clinical Considerations
•
HIV RNA and CD4 assays are
independently predictive of risk of
disease progression
•
Both help determine when to start and
when to change ARV therapy
•
A 5-fold change in HIV RNA copies/mL in
infants or 3-fold change in children is
biologically and clinically significant
HIV RNA and Children:
Clinical Considerations
• Low levels at birth rise to >100,000
copies/mL to several million copies
within the first 1–2 months of life
• Without treatment, very slow decline
over several years to reach “set point”
HIV RNA and Children:
Clinical Considerations
•
Children >12 months with HIV RNA
>100,000 copies/mL are at higher risk
for disease progression and death
– Predictive value of HIV RNA in infants <12 months old
less than older children
– In infants, HIV RNA levels are much higher and overlap
with rapid and non-rapid progressors
– CD4+ counts/percentages may be more useful in
evaluating risk in infants <12 months than HIV RNA; in
older children both parameters are useful
HIV RNA in Children:
Clinical Considerations
• Moderate predictive value of specific HIV RNA
levels for disease progression/death in
individual child
• HIV RNA levels difficult to interpret in first
year of life
• CD4+ and HIV RNA level provide
complimentary and independent information
about prognosis
• Assess HIV RNA every 3-4 months
HIV RNA and Children:
Clinical Considerations
•
Obtain 2 baseline HIV RNA tests when child
is clinically stable
•
Confirm HIV RNA changes with a second
test before making therapy changes
•
Consult pediatric HIV specialist when
interpreting HIV RNA for clinical decisionmaking
Antiretroviral Treatment
Guidelines for Children
with HIV Infection
Decision Factors about
ARV Initiation in Children
•
Disease severity and risk of
progression—presence/hx of
serious illness, CD4+ count, HIV
RNA
•
Availability of appropriately
formulated and palatable drugs
Decision Factors about
ARV Initiation in Children
•
Complexity of regimen and
potential adverse effects
•
Effect of initial choice on later
therapeutic options
Decision Factors about ARV
Initiation in Children
•
•
•
Presence of comorbidities (e.g. TB,
Hep B or C, or chronic renal/liver
disease)
Potential ARV interaction with
child’s other medications
Ability of the child and caregiver to
adhere to the regimen
Early Initiation of Therapy:
Potential Advantages
Starting ARVs in the asymptomatic patient:
– Controls viral replication while genetic
quasispecies are relatively homogeneous and
before significant viral mutations occur
– Could control development of heterogeneous
viral strains/mutations
– Potentially leads to less drug resistance
– Could lower “viral setpoint”fewer viral strains
– Slows immune system destruction preserving
immune function and preventing clinical
progression
Delayed Initiation of Therapy:
Potential Advantages
Delaying ARV therapy until
symptomatic:
– Could reduce evolution of drug-resistant
virus due to lack of drug selection pressure
exerted by early ARV use
– May support greater adherence when
symptomatic
– Reduces or delays adverse effects of ARVs
ARV Therapy for Infants
<12 Months
•
Risk of disease progression is inversely
correlated with age
•
Limited data on rapid v. slower disease
•
Limited clinical trial data on early
aggressive therapy
•
Limited information on drug dosing
•
Potential ARV toxicities over the long term
ARV Therapy for Infants
<12 Months
The Working Group recommends:
•
Initiate treatment for any infant with
clinical or immunologic symptoms
•
Consider treatment for infants who
are asymptomatic with normal
immune function
Indications for Initiation of ARV
Therapy in Children <12 Months of
Age
Plasma HIV
RNA Copy Recommend
Number1
Clinical
Category
CD4+ Cell
Percentage
Symptomatic
(Clinical
Category A, B,
or C)
<25%
(Immune
Category 2 or 3)
Any Value
Treat
>25%
(Immune
Category 1)
Any Value
Consider
Treatment2
OR
Asymptomatic
AND
(Clinical
Category N)
ARV Therapy for Children
Age 12 Months and Older
• Risk of disease progression is less in older
children than in infants
• Children with fewer clinical symptoms or
only moderate immune suppression are at
lower risk for progression than those with
more advanced clinical symptoms/immune
disease
• In children >12 months, plasma HIV RNA may
provide information about progression risk
as an adjunct to clinical/immune parameters
and can assist in making ARV decisions
ARV Therapy for Children
Age 12 Months and Older
The Working Group recommends:
•
Start treatment in children with AIDS or
severe immune suppression
•
Consider treatment for children with
– Mild-moderate clinical symptoms
– Moderate immune suppression and/or
– Confirmed plasma HIV RNA level >100,000
copies/mL
ARV Therapy for Children
Age 12 Months and Older
•
Defer treatment in asymptomatic
children with normal immune status
with low risk of clinical disease
(HIV RNA <100,000 copies/mL) when
adherence factors favor postponing
•
Monitor virologic, clinical, and
immunologic status
ARV Therapy for Children
Age 12 Months and Older
• Factors to consider in deciding when to
initiate therapy
– Increasing HIV RNA levels (>100,000 copies/mL)
– Rapidly declining CD4+ count or percentage to
values approaching severe suppression
– Development of clinical symptoms
– Ability of caregiver and child to adhere to
regimen