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Diagnosis of HIV Infection in Infants and Children

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Title: Diagnosis of HIV Infection in Infants and Children


1
Diagnosis of HIV Infection in Infants and
Children

2
Objectives
  • 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

3
Goal 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

5
It 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

6
Complexities 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

7
Complexities 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

8
Antibody 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
9
Complexities 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

10
HIV 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

11
DNA PCR for Infant Diagnosis
At 4-6 weeks of age sensitivity of DNA PCR is
96-98
Dunn D, AIDS 1995, 9F7
12
Diagnosing HIV in Infants 13
How 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

  • 14
    How 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
    15
    What if the DNA PCR isPositive?
    • If the HIV DNA PCR result is
    • POSITIVE
    • the baby is presumed to be
    • HIV-INFECTED

    16
    What 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

    17
    What 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

    18
    Diagnostic 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.
    19
    What 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

    20
    What 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

    21
    What 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

    22
    Diagnostic 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
    23
    What 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

    24
    Diagnostic 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
    25
    What 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

    26
    What 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

    27
    What 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

    28
    Diagnostic 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
    29
    What 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

    30
    Diagnostic 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
    31
    What 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

    32
    What 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

    33
    Diagnostic 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
    34
    Infant Diagnosis for children over 18 months of
    age
    35
    Diagnosing 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

    36
    Diagnostic 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
    37
    Summary 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
    38
    Summary 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

    39
    Summary 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

    40
    If 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

    41
    Presumptive 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

  • 42
    Infants 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

    43
    Early 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

    44
    Critical 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?

    45
    Critical 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

    46
    Critical 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

    47
    Programmatic 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

    48
    Conclusion
    • 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
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