Title: Diagnosis of HIV Infection in Infants and Children
1Diagnosis of HIV Infection in Infants and
Children
2Objectives
- This presentation will
- Review key concepts in diagnosing HIV infection
in infants and young children - Review virologic and antibody tests
- Explain the algorithms for diagnosing HIV in
infants and young children - Describe the use of clinical criteria to identify
presumed severe HIV-infection
3Goal of Early Infant Diagnosis
- The primary goal of early infant diagnosis to
identify the HIV-infected child early, prior to
the development of clinical disease during the
first months of life. The goal is NOT to exclude
infection in infants. - Diagnosis should be early enough so interventions
and treatment can be started
4 Objectives for Early HIV Diagnosis
- To identify HIV-infection in infants as early as
possible - This is done through laboratory diagnosis and
good clinical reasoning - To reduce pediatric mortality and morbidity
- To initiate ART in an infant with rapidly
progressing HIV-disease
5It is important to remember
- Babies can acquire HIV infection during
- Pregnancy Labor
delivery Breast feeding - Keeping this in mind will help you to understand
infant diagnosis
6Complexities of Infant Diagnosis
- HIV infection is difficult to diagnosis in
infants - Routine HIV antibody tests cannot be used
- Specialized virologic tests are necessary
- Clinical diagnosis requires frequent and close
follow-up of the infant - HIV infection is difficult to exclude in infants
- Infants who breastfeed continue to be at risk for
acquiring HIV infection - Risk of infection continues throughout duration
of breastfeeding - Diagnosis of infants is an ongoing process and
depends on good clinical reasoning as well as
laboratory results
7Complexities of HIV Diagnosis Antibody Tests
- All infants born to HIV mothers will test HIV
antibody positive - Maternal HIV antibody (IgG) is transferred across
the placenta during pregnancy - A positive HIV antibody test will not distinguish
whether or not the infant is HIV-infected rather
it shows that - Mother is HIV-infected
- Infant is at risk for HIV infection
- If the child is not infected the HIV antibody
fades during first 6 - 18 months of life - Most uninfected infants test negative by 12
months of age - All uninfected infants test negative by 18 months
of age
8Antibody Detection in 77 HIV-Exposed, Uninfected
Infants in South Africa
Rapid Ab can be used to exclude infection around
12-18 months of age
Moodley D, PIDJ 199514850
9Complexities of HIV Diagnosis Virologic Testing
- Specialized virologic tests are needed to
definitively diagnose HIV infection in infants - DNA PCR
- RNA PCR
- p24Antigen
- Antibody testing can be used to diagnose HIV
infection in children 18 months of age
10HIV DNA PCR
- HIV DNA PCR is a special laboratory test that
detects pieces of the viral gene that are
incorporated in the human blood cell - By comparison, HIV Antibody testing detects the
antibody that the body makes in response to the
HIV virus - Sensitivity of HIV DNA PCR increases with time
during the first month of life - The infant may have HIV infection but there may
not be enough virus in the blood to detect it at
birth. It becomes easier to find/detect as the
infant gets a little older
11DNA PCR for Infant Diagnosis
At 4-6 weeks of age sensitivity of DNA PCR is
96-98
Dunn D, AIDS 1995, 9F7
12Diagnosing HIV in Infants
13How to Approach Diagnosis of HIV Infection in
Children
Know that the child is at risk for HIV infection Born to an HIV-infected woman Tests HIV-antibody positive Pay close attention to the childs clinical
status and growth pattern Use special virologic tests 14How to Use Virologic Testing
- Every HIV-exposed baby should have a DNA PCR test
- At 4-6 weeks of life
- or
- At first health encounter (if 6 weeks of age)
-
if 9 months, screen with rapid antibody first
15What if the DNA PCR isPositive?
- If the HIV DNA PCR result is
- POSITIVE
- the baby is presumed to be
- HIV-INFECTED
16What should you do if the DNA PCR is Positive?
- Refer the baby for HIV care treatment
- Dont wait!
- Start or continue cotrimoxazole
- Repeat DNA PCR to confirm results
- Encourage mother to continue breastfeeding
17What should you tell the care giver if the
initial PCR test is positive?
- HIV has been detected in your infants blood
- This means that your child has HIV infection
- We will repeat the test to make sure that the
result is correct - We will check your baby carefully and refer you
and your baby to a clinic where there are doctors
and nurses who are experts in taking care of
children with HIV - The doctors and nurses will teach you how to care
for yourself and the baby so you both stay healthy
18Diagnostic Algorithm for Infants age
Infant 4-6 weeks of age or at first health
encounter
HIV DNA PCR
HIV DNA PCR POSITIVE Presumed HIV-INFECTED
- Do not WAIT
- Refer for HIV care treatment IMMEDIATELY
- Start/continue cotrimoxazole prophylaxis
- Do confirmatory HIV DNA PCR and send results to
CTC
Confirm HIV exposure with rapid antibody test
if 9 months of age. If antibody negative, and
infant is still breastfeeding, repeat rapid
antibody test 6 weeks after complete cessation
of breast feeding.
19What if the DNA PCR isNegative?
- If the HIV DNA PCR result is
- NEGATIVE
- the baby is presumed NOT to be HIV-infected
- NOTE Infants who are still breastfeeding are at
continued risk for acquiring HIV infection
20What should you do if the DNA PCR is Negative?
- Continue close follow-up
- Continue cotrimoxazole (CTX)
- Encourage continued exclusive breastfeeding (EBF)
through 6 months of age
21What should you tell the care giver if the
initial PCR test is negative?
- We did not find the HIV virus in your babys
blood - Since you are breastfeeding, your baby may still
get the virus from the breast milk - We will have to keep checking on him/her and look
for the virus until 6 weeks after s/he stops
breastfeeding - If he or she stays well, we will not test again
until at least 6 weeks after you wean the baby
from the breast - If your baby gets get sick, we will repeat the
special test again to check for the virus - You need to keep bringing your child for check
ups and continue cotrimoxazole
22Diagnostic Algorithm for Infants age
Infant 4-6 weeks of age or at first health
encounter
HIV DNA PCR
HIV DNA PCR POSITIVE HIV-INFECTED
DNA PCR NEGATIVE
- Do not WAIT. Refer for HIV care treatment
IMMEDIATELY - Start/continue cotrimoxazole prophylaxis
- Do confirmatory HIV DNA PCR and send results to
CTC
Continue CTX and clinical follow-up
23What if the Initial DNA PCR isNegative and the
child is WELL?
- Repeat HIV testing 6 weeks after weaning using
- Rapid HIV Antibody Test
- NOTE Breastfeeding babies remain at risk for
acquiring HIV
24Diagnostic Algorithm for Infants age
Infant 4-6 weeks of age Or at first health
encounter
HIV DNA PCR
DNA PCR NEGATIVE
HIV DNA PCR POSITIVE HIV-INFECTED
Continue CTX and close follow-up
- Do not WAIT. Refer for HIV care treatment
IMMEDIATELY - Start/continue cotrimoxazole prophylaxis
- Do confirmatory HIV DNA PCR and send results to
CTC
WELL Infant
HIV Rapid Antibody 6 weeks after weaning
25What if the HIV Antibody is Negative?
- If the HIV Antibody result is
- NEGATIVE
- the baby is presumed NOT to be HIV-infected
- NOTE At this point, the baby may be discharged
from the program
26What if the HIV Antibody isPositive?
- If the HIV antibody result is Positive and the
baby is 18 (older than) months of age the baby
is presumed to be - HIV-INFECTED
- Refer for HIV care and treatment
27What if the HIV Antibody isPositive?
- If the HIV antibody is positive and the baby is
- Repeat HIV DNA PCR
- NOTE Maternal antibody can persist until 18
months of age
28Diagnostic Algorithm for Infants age
Infant 4-6 weeks of age Or at first health
encounter
HIV DNA PCR
HIV DNA PCR POSITIVE HIV-INFECTED
DNA PCR NEGATIVE
Continue CTX and clinical follow-up
- Do not WAIT. Refer for HIV care treatment
IMMEDIATELY - Start/continue cotrimoxazole prophylaxis
- Do confirmatory HIV DNA PCR and send results to
CTC
WELL Infant
HIV Rapid Antibody Test 6 weeks after weaning
HIV Antibody Positive_at_
HIV Antibody Negative UNINFECTED
HIV DNA PCR
Discharge from program
_at_ Positive HIV Antibody diagnoses HIV infection
if 18mo at time of weaning It is not necessary
to test with DNA PCR
29What if the Initial DNA PCR is Negative but the
child is ILL?
- If the HIV DNA result is negative, but the child
develops HIV symptoms - Oral thrush
- Pneumonia
- Poor growth
- Developmental delay
- Chronic diarrhea
- REPEAT HIV DNA PCR TESTING
- NOTE Breastfeeding babies remain at risk for
acquiring HIV
30Diagnostic Algorithm for Infants age
Infant 4-6 weeks of age or at first health
encounter
HIV DNA PCR
HIV DNA PCR POSITIVE HIV-INFECTED
DNA PCR NEGATIVE
Continue CTX and clinical follow-up
- Do not WAIT. Refer for HIV care treatment
IMMEDIATELY - Start/continue cotrimoxazole prophylaxis
- Do confirmatory HIV DNA PCR and send results to
CTC
ILL Infant
WELL Infant
HIV Rapid Antibody 6 weeks after weaning
Repeat DNA PCR
31What if the 2nd DNA PCR isPositive?
- If the HIV DNA PCR result is
- POSITIVE
- the baby is presumed to be
- HIV-INFECTED
- Refer for HIV care and treatment
32What if the 2nd DNA PCR isNegative?
- If the HIV DNA PCR result is
- NEGATIVE
- the baby is presumed NOT to be HIV-infected
- NOTE If the baby is still breastfeeding repeat
rapid HIV test 6 weeks after weaning - Refer the infant for further evaluation
33Diagnostic Algorithm for Infants age
Infant 4- 6 weeks of age or at first health
encounter
HIV DNA PCR
DNA PCR NEGATIVE
HIV DNA PCR POSITIVE HIV-INFECTED
Continue CTX and close follow-up
- Do not WAIT. Refer for HIV care treatment
IMMEDIATELY - Start/continue cotrimoxazole prophylaxis
- Do confirmatory HIV DNA PCR and send results to
CTC
ILL Infant
WELL Infant
Repeat DNA PCR
HIV Rapid Antibody 6 weeks post weaning
HIV DNA PCR NEGATIVE
HIV DNA PCR POSITIVE HIV-INFECTED
Refer for HIV care treatment
Refer for consultation
34Infant Diagnosis for children over 18 months of
age
35Diagnosing HIV in the Child 18 Months
- HIV antibody should be used to diagnose HIV
infection in children 18 months of age - Children 18 months with positive antibody test
have HIV infection - A positive antibody test should be confirmed by
duplicate testing - A negative antibody test in children 18 months
excludes HIV infection - Except in cases of continued breastfeeding.
Antibody should be repeated at least 6 weeks post
cessation of breastfeeding
36Diagnostic Algorithm for Children 18 months of
age
Child 18 months of age
Rapid HIV Antibody Test
HIV Antibody NEGATIVE
HIV Antibody POSITIVE HIV-INFECTED
Refer for HIV care treatment
Non-breastfeeding child UNINFECTED
Breastfeeding child remains at risk of infection
Repeat HIV Rapid Antibody 6 weeks after weaning
HIV Antibody POSITIVE HIV-INFECTED
HIV Antibody NEGATIVE UNINFECTED
Refer for HIV care treatment
37Summary How to Use DNA PCR Testing
- Every HIV-exposed baby should have a DNA PCR test
- At 4-6 weeks of life or at first health encounter
if 6 weeks of age - Any infant with an initial negative DNA PCR who
develops signs and symptoms of HIV infection - Testing prior to 4 weeks in HIV-exposed infant
who is symptomatic - In a baby weeks after weaning
-
if 6 weeks at first visit, screen with rapid
antibody first
38Summary When should you repeat the DNA PCR?
- HIV antibody positive infant with signs and symptoms of HIV infection
- Children antibody test 6 weeks post-weaning
- Confirm any initial positive virologic test
39Summary When should you use HIV Antibody Tests?
- Children
- Determine HIV exposure in infants born to women
of unknown HIV status - Exclude infection in an infant who is not
breastfed or 6 weeks post-weaning - Exclude HIV infection in children 9 months of
age - Children 18 months of age
- Confirm HIV infection
40If virologic test results dont match the
clinical picture
- Clinical findings can suggest the diagnosis of
HIV infection even when virologic tests are
negative - Rapid disease progression is common in
HIV-infected infants - Growth failure and delay or loss of developmental
milestones are seen frequently in infants with
rapid progression - Use CD4 to assess immunologic status
- Low CD4 is consistent with HIV diagnosis
- Other diseases can have similar manifestations
and should be ruled out if possible - Repeat virologic testing should be considered
- HIV antibody testing should be repeated at 18
months to confirm infection status
41Presumptive Clinical Diagnosis of HIV in children
Clinical algorithms are rarely more than 70
sensitive for diagnosis of HIV infection. They vary with age especially in children less
than 12 months Screen with antibody to confirm HIV exposure Confirmation of HIV diagnosis should be sought as
soon as possible 42Infants Virologic Testing is not Available
- WHO criteria for Presumptive Clinical Diagnosis
of HIV - Confirmed HIV antibody positive
- Symptomatic with two or more of the following
- Oral thrush
- Severe pneumonia()
- Severe sepsis()
- Other factors that support the diagnosis include
- Recent HIV-related maternal death
- Advanced HIV in the mother
- CD4
43Early and Frequent Clinical Evaluation
- Close monitoring of growth and development
- Early identification of disease signs symptoms
- Use of symptom checklist, monitor growth and
development closely - Listen to the parent
- Common illnesses can mimic symptoms of
HIV-infection (growth failure, recurrent fevers,
diarrheal illnesses) - Cotrimoxazole prophylaxis for all HIV-exposed
infants until HIV has been excluded - Vaccinations, per local guidelines
44Critical Elements for Early Infant Diagnosis
- Remember
- Virologic tests should always be interpreted in
the context of the clinical presentation of the
child. - Dont hesitate to question the results if they
dont make sense. Errors do occur! - Are results valid?
- Do the results make sense given the childs
health? - Is there a laboratory problem?
- Could there be a specimen mix-up?
45Critical Elements for Early Infant Diagnosis
- Early and frequent clinical evaluations
- Good Clinical Reasoning can identify children at
high risk for HIV disease rapid progression
during the first months of life - Early virologic testing
- Good communication with family is critical
- Team members should emphasize importance of
- Determining HIV status
- Adherence to visit schedule
- Identifying signs and symptoms
- Administering Cotrimoxazole prophylaxis
46Critical Elements for Early Infant Diagnosis
- Children who have early virologic testing must
return to the clinic for results - Both infants with positive and negative results
- Infants who are breastfeeding must be retained in
care until they are weaned and a final infection
status is determined - Infant and children who are identified as
HIV-infected will need to be linked to pediatric
HIV care and treatment service
47Programmatic Barriers
- When an infant is seen at a maternal child health
clinic (or other site of care), how will the
clinician know that s/he is HIV-exposed? - Coordination between the ANC, MCH, and CTC
- Use of rapid antibody to identify mothers and
exposed infants if maternal HIV status is not
known - Routine testing of children of adults in HIV
care and treatment programs - Infants are not coming back for results
- Use appointment systems
- Monitor missed appointments
- Enhance parent/family education and support
- Reminders for parents and care givers
- Active outreach after missed visits
48Conclusion
- Clinical reasoning is critical to diagnosing
infants with HIV - Early virologic testing should be used to
identify the infected infant at highest risk for
disease progression - Specialized virologic tests are used to diagnose
HIV infection in a child - Virologic tests may be unreliable or unavailable,
highlighting the importance of clinical
evaluation - The multidisciplinary team has numerous critical
roles in this process - The parent or caretaker is the key player, and
must be educated and supported on this
logistically, emotionally, socially and medically
complicated path