The HIV Exposed Infant Morning Report October 2005

The HIV Exposed
Infant
Morning Report
October 2005
Background
‹ In
the US, more than 90% of
reported cases of AIDS in children
are due to perinatal transmission
‹ The other 10% are from blood
transfusions, sexual abuse and
unknown sources
‹ All pregnant women should be
offered counseling and testing for
HIV infection during pregnancy
Prevention of Transmission
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In 1994, the US Public Health Service published guidelines
for use of zidovudine in the HIV infected woman during
pregnancy to decrease the risk of perinatal transmission of
HIV
In 1995, the AAP and US Public Health Service
recommended documented, routine HIV education and
testing with consent for all pregnant women in US
Incorporation of these guidelines has resulted in a dramatic
decrease in the rate of perinatal HIV transmission and a
75% decrease in reported cases of pediatric AIDS
CDC estimates that the rate of new cases of perinatal HIV
infection has decreased from 1500 to 300-400 per year
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Effective August 2003
Enacted to prevent mother-to-newborn
transmission of HIV
Health care professionals are required to offer
HIV counseling and strongly encourage voluntary
testing to all pregnant women and their infants
Counseling and testing should be offered
prenatally, during delivery and post-partum
All testing must be obtained by consent
Mother must sign written consent before HIV test
If mother’s status is unknown, consent for testing
infant is presumed and should be done unless
mother refuses in writing
HIV Counseling
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All HIV counseling of pregnant women should be
done in accordance with the AIDS Confidentiality
Act and should include:
– Benefits of HIV testing for pregnant women, including
opportunity for prevention of transmission
– Benefit of testing infant, including interventions to
prevent transmission
– Side effects of interventions
– The confidentiality provisions that relate to HIV and
AIDS
– The voluntary nature of testing, including the
opportunity to refuse testing of infant in writing
Epidemiology
In 1999, 41% of young adults 13-24 years
old with AIDS were females
‹ In US, approximately 25% of HIV
transmission is estimated to occur among
people younger than 21 years of age
‹ Sexually active youth everywhere are at
risk unless barrier protection is used
‹ Heterosexual contact surpassed IV drug
use as the predominant mode of HIV
transmission for women with AIDS in 1992
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Epidemiology
‹ The
transmission rate of HIV in
infected, untreated pregnancies is
approximately 25%
‹ The
transmission rate with antenatal,
intrapartum and infant prophylactic
antiretroviral therapies is less than
2%
Epidemiology
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Studies on timing of transmission suggest that in
a nonbreastfeeding population, 25-40% of
transmission occurs in utero
Absolute risk for in utero transmission is 5%,
intrapartum transmission is 13-18%
Maternal viral load is critical determinant of
perinatal HIV transmission
Other factors: CD4+ count, advanced maternal
illness, intrapartum events resulting in increased
exposure to maternal blood, placental
inflammation, premature delivery, prolonged
labor, prolonged ROM
Epidemiology
Women who seroconvert during
pregnancy may be at higher risk for in
utero transmission
‹ Reduction of maternal HIV viral load to a
nondetectable level is the key to
preventing vertical transmission
‹ C/S may be helpful in preventing
peripartum transmission
‹ Postpartum transmission occurs through
breastfeeding
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– Worldwide, 1/3 to 1/2 of transmission
– In US, it is possible to offer safe alternative
HIV Tests
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Expedited enzyme immunoassays
– Uses first step of standard laboratory HIV-1 antibody
testing
– Positive and negative results within 24hr
– A positive result must be confirmed by Western blot
analysis
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Rapid test kit
– Tests a single specimen for HIV-1 antibodies
– Results available within minutes to 2 hrs
– OraQuick Rapid and Single Use Diagnostic System
(SUDS) HIV-1 tests are licensed in US
– Rapid should be confirmed by standard testing
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If positive test results, a confirmatory
supplemental test is required
HIV Tests
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Antibody-based assays (EIA, Western Blot)
cannot be used in infancy due to transplacental
transfer of antibody
HIV nucleic acid detection by PCR assay of DNA
from peripheral blood is the preferred test for
diagnosis of infants
– Available within 24hours
– Approx 30% of infants with infection will have a positive
test by 48 hours
– Single assay has sensitivity of 95%, specificity of 97% in
infants 1 to 36 months of age
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Virus isolation by culture is expensive and takes
up to 28 days for results
p24 antigen is less sensitive
HIV RNA PCR assay
‹ Can
diagnose HIV infection only if
result is positive
‹ This test can be negative in HIVinfected individuals
‹ Licensed by FDA only in quantitative
format
‹ Currently used for quantifying the
amount of virus present as a
predictor of disease progression
HIV Testing of the Infant
If mothers status is unknown:
‹ Test the infant with maternal consent
(right of refusal)
‹ HIV DNA PCR should be sent during
the first 48 hours of life
‹ Some states mandate testing of all
infants whose maternal status is
unknown
HIV Diagnosis
‹ HIV
DNA PCR for diagnosis at
< 48 hours of life
‹ 14 days
‹ 1 to 2 months
‹ 2 to 4 months
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‹ If
positive test, repeat test on second
blood sample
‹ Infection = 2 separate samples
positive on 2 separate dates
HIV Diagnosis
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Infection can be excluded if:
2 or more negative HIV DNA PCR tests at age
> 1 month PLUS a negative test at age >4
months
OR
2 or more samples negative for HIV antibody
at >6 months (interval of one month)
Laboratory Findings
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In a perinatally infected infant, notable
findings may include
– High viral load (HIV RNA PCR) that does not
decrease rapidly in first year of life
– Increasing loss of cell immunity
– Lymphocyte count may be normal but eventual
decrease in CD4+ results (age related norms)
– T-suppressor CD8+ cells increase initially and
are not depleted until late in course of
infection
– Elevated IgG and IgA levels are manifestations
of humoral immune dysfunction
Antiretroviral Agents
Three categories of drugs each with a site
of action against HIV replication
‹ Reverse transcriptase inhibitors target an
enzyme that converts HIV RNA to DNA for
transcription by the host cell genome
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– Nucleoside analogue agents (Zidovudine)
– Nonnucleoside analogue agents (Nevirapine)
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Blocking the protease enzyme is a second
site of action
– Protease inhibitors (indinavir)
Antiretroviral Prophylaxis
If Maternal HIV known during
Pregnancy
Antepartum: Oral Zidovudine (ZDV)
beginning at 14 to 34 weeks gestation
continuing through pregnancy
‹ Intrapartum: IV ZDV infusion until
delivery
‹ Postpartum: Oral ZDV syrup
(2mg/kg/dose Q 6 hrs) to newborn infant
within 6-12h of birth for the first 6 weeks
of life
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*this regimen decreased transmission by 2/3 in
clinical trials
Antiretroviral Prophylaxis
Maternal HIV diagnosed during
Labor
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If maternal HIV status is determined only at the
time of labor and delivery, any of the following
regimens have been shown to be effective for
prevention of transmission:
– Maternal oral dose of nevirapine (NVP) at onset of labor
followed by a single oral dose of NVP for infant at 48-72
hr
– Intrapartum oral ZDV and lamivudine (3TC) followed by
1 week of oral ZDV and 3TC for infant
– Intrapartum intravenous ZDV followed by 6 weeks of
ZDV for infant
– Combination of ZDV and NVP regimen
Postnatal Antiretroviral Prophylaxis
‹ When
birth:
HIV status known only after
– No prenatal or intrapartum therapy
received
– Data suggest that 6 weeks of ZDV
prophylaxis given to infant may provide
some protection if given within first 24
hours
– Some may add additional antiretroviral
drug, as in post exposure prophylaxis
Cesarean Section
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Rate of transmission decreased by 50% (in
absence of ZDV) when delivery was by elective
C/S before ROM and onset of labor
With antiretroviral therapy and C/S, rate
decreased to 2%
Vaginal delivery and antiretroviral therapy had
rates of 7%
If HIV RNA level is undetectable, rates of
perinatal transmission is low even with vaginal
delivery
– C/S may not outweigh risk of operation
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ACOG recommends counseling women with viral
loads > 1000/ml about the benefit of C/S delivery
Management of HIV Infected Infant
Infection = 2 separate HIV DNA PCR
assays positive on 2 separate dates
‹ Consult HIV specialist
‹ Initiate treatment in all HIV-infected
infants < 12 months who have clinical or
immunologic abnormalities
‹ Consider treatment in those < 12 months
that are asymptomatic
‹ Recommendation based on rapid disease
progression in infants
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HIV Antibody Testing
In HIV exposed infants, serologic testing
after 12 months of age is used to confirm
that maternal ab transferred have
disappeared
‹ If antibodies negative and previous HIV
DNA PCR tests were negative, child is not
infected
‹ If HIV antibody is + at 12 months, repeat
test at 18 months
‹ Positive HIV antibodies at > 18 months
indicates infection
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PCP Prophylaxis
‹ PCP
is the most serious opportunistic
infection in HIV infected children
‹ It is recommended that PCP
prophylaxis be started at 4-6 weeks
of age (near completion of ZDV
prophylaxis)
‹ Discontinue prophylaxis when HIV
infection can be reasonably excluded
Immunizations
‹ All
routine immunizations should be
given to HIV exposed infants
‹ For HIV infected infants, standard
immunizations are recommended
including:
– Influenza if CD4+ counts are not low
– Varicella if CD4+ counts are normal
References
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Pickering, L and the American Academy of Pediatric. Red
Book 2003 Report of the Committee on Infectious Diseases
pp.360-380.
Burchett, S. HIV Infection in Infants, Children, and
Adolescents. Pediatrics in Review 2003; 24 (6)
King, S and Committee on Pediatric AIDS and Canadian
Paediatric Society, Infectious Diseases and Immunization
Committee. Evaluation and Treatment of the Human
Immunodeficiency Virus-1 – Exposed Infant. Pediatrics
2004; 114; 497-505.
Mofenson, LM and the Committee on Pediatric
AIDS. Technical Report: Perinatal Human Immunodeficiency
Virus Testin and Prevention of Transmission. Pediatrics
2000; 106; 88.
The Illinois Prenatal HIV Prevention Law. Guidelines for
Delivery of Care.
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