1. HIV exposure in the newborn Case Conference
Shanika Uduwana
PGY 2

2. Case 1 11 day old born to an HIV infected mother who found out she was HIV- infected during this pregnancy and did not present to prenatal care until 32 weeks of gestation. One month prior delivery viral load mother HBsAg, RPR negative, Hx of chlamydia and HPV
Case 2 3 week old born to an HIV infected mother whose HIV viral load was undetectable during the third trimester of pregnancy. She is HBsAg, RPR, anti HCV negative. Mother diagnosed with latent TB infection during the 2nd trimester and was started on INH.

3. Questions
What is the HIV testing guideline for pregnant women ? What are t he chance s that the baby will get infected? What is the mode of delivery during labor? Are we going to start the baby on medications? Are we going to test the baby? If yes, what test are we going to do ? And when?

4. Pediatric AIDS cases account for fewer than 1% of all reported cases of AIDS in the United States. Since the mid 1990s, the number of reported pediatric AIDS cases decreased significantly, primarily because of interruption of mother-to-child transmission of HIV.

5. The decrease in rate of mother-to-child transmission of HIV in the United States was attributable to development and implementation of antenatal HIV testing programs and of interventions to prevent transmission:
Antiretroviral (ARV) prophylaxis during the antepartum, intrapartum, and postnatal periods;
Cesarean delivery before labor and before rupture of membranes
Complete avoidance of breastfeeding..

6. Human Immunodeficiency Virus Infection Figure 50.
Committee on Infectious Diseases et al. Red Book Online
Copyright © American Academy of Pediatrics

7. Human Immunodeficiency Virus Infection Figure 47.
Committee on Infectious Diseases et al. Red Book Online
Copyright © American Academy of Pediatrics

8. HIV testing guidelines for pregnant women
Timing of HIV Testing To promote informed and timely therapeutic decisions, health-care providers should test women for HIV as early as possible during each pregnancy. Women who decline the test early in prenatal care should be encouraged to be tested at a subsequent visit. A second HIV test during the third trimester, preferably <36 weeks of gestation, is cost-effective even in areas of low HIV prevalence and may be considered for all pregnant women. Rapid Testing During Labor Any woman with undocumented HIV status at the time of labor should be screened with a rapid HIV test unless she declines (opt-out screening). Reasons for declining a rapid test should be explored (see Addressing Reasons for Declining Testing). Immediate initiation of appropriate antiretroviral prophylaxis should be recommended to women on the basis of a reactive rapid test result without waiting for the result of a confirmatory test. Postpartum/Newborn Testing When a woman's HIV status is still unknown at the time of delivery, she should be screened immediately postpartum with a rapid HIV test unless she declines . When the mother's HIV status is unknown postpartum, rapid testing of the newborn as soon as possible after birth is recommended so antiretroviral prophylaxis can be offered to HIV-exposed infants. Women should be informed that identifying HIV antibodies in the newborn indicates that the mother is infected.
A second HIV test during the third trimester is recommended for women who meet one or more of the following criteria: --- Women who receive health care in jurisdictions with elevated incidence of HIV or AIDS among women aged years. In 2004, these jurisdictions included Alabama, Connecticut, Delaware, the District of Columbia, Florida, Georgia, Illinois, Louisiana, Maryland, Massachusetts, Mississippi, Nevada, New Jersey, New York, North Carolina, Pennsylvania, Puerto Rico, Rhode Island, South Carolina, Tennessee, Texas, and Virginia.† --- Women who receive health care in facilities in which prenatal screening identifies at least one HIV-infected pregnant woman per 1,000 women screened Women who are known to be at high risk for acquiring HIV (e.g., injection-drug users and their sex partners, women who exchange sex for money or drugs, women who are sex partners of HIV-infected persons, and women who have had a new or more than one sex partner during this pregnancy) Women who have signs or symptoms consistent with acute HIV infection. When acute retroviral syndrome is a possibility, a plasma RNA test should be used in conjunction with an HIV antibody test to diagnose acute HIV infection (96

9. The role of ARV therapy
Most mother-to-child transmission occurs intrapartum (80%), with smaller proportions of transmission occurring in utero (mostly in the third trimester) and postnatally through breastfeeding.
The risk of infection for an infant born to an HIV-seropositive mother who did not receive interventions to prevent transmission is estimated to range from 12% to 40% and is thought to average between 21% and 25% in the United States.
Combination ARV regimens during pregnancy have been associated with lower rates of mother-to-child transmission than has zidovudine alone. Currently in the United States, most HIV-infected pregnant women receive 3-drug combination ARV regimens either for treatment of their own HIV infection or, if criteria for treatment are not yet met, for prevention of mother-to-child transmission of HIV (in which case the drugs are stopped after delivery)

10. Risk factors for mother-to-child transmission of HIV
Amount of virus to which the child is exposed (especially the maternal viral load; a higher maternal viral load is associated with a lower maternal CD4+ T- lymphocyte count and with more advanced maternal clinical disease)
Duration of such exposure (eg, duration of ruptured membranes or of breastfeeding, vaginal versus cesarean delivery before labor and before rupture of membranes)
Factors that facilitate the transfer of virus from mother to child (eg, maternal breast pathologic lesions, infant oral candidiasis
Characteristics of the virus and the child's susceptibility to infection are also important.
Of note, although maternal viral load is a critical determinant affecting the likelihood of mother-to-child transmission of HIV, transmissions have been observed across the entire range of maternal viral loads. The risk of mother-to-child transmission increases with each hour increase in the duration of rupture of membranes, and the duration of ruptured membranes should be considered when evaluating the need for special obstetric interventions.

11. Role of C-section
Cesarean delivery performed before onset of labor and before rupture of membranes has been shown to reduce mother-to-child intrapartum transmission. Current US guidelines recommend cesarean delivery before onset of labor and before rupture of membranes for HIV-infected women with a viral load greater than 1000 copies/mL (irrespective of use of ARVs during pregnancy) and for women with unknown viral load near the time of delivery

12. Role of breastfeeding
Postnatal transmission to neonates and young infants occurs mainly through breastfeeding. Worldwide, an estimated one third to one half of cases of mother-to-child transmission of HIV occurs as a result of breastfeeding. HIV genomes have been detected in cell-associated and cell-free fractions of human milk. In the United States, HIV-infected mothers are advised not to breastfeed, because safe alternatives to human milk are available readily. Because human milk cell- associated HIV can be detected even in women receiving antiretroviral therapy (ART), replacement (formula) feeding continues to be recommended for US mothers receiving ART.
In resource-limited locations, women whose HIV infection status is unknown are encouraged to breastfeed their infants exclusively for the first 6 months of life, because the morbidity associated with formula feeding is unacceptably high. In addition, these women should be offered HIV testing. For HIV-infected mothers, 2010 WHO guidelines recommend that exclusive breastfeeding be provided for the first 6 months of life. The introduction of complimentary foods should occur after 6 months of life, and breastfeeding should continue through 12 months of life. Breastfeeding should be replaced only when a nutritionally adequate and safe diet can be maintained without human milk. In areas where ARVs are available, infants should receive daily nevirapine prophylaxis until 1 week after human milk consumption stops, or mothers should receive ARV prophylaxis (consisting of an ART regimen) for the first 6 months of their infants' lives. For infants known to be HIV-infected, mothers are encouraged to breastfeed exclusively for the first 6 months of life, and after the introduction of complimentary foods, they should continue to breastfeed up to 2 years of age, as per recommendations for the general population.

13. Testing the new born Need for early diagnosis :
Infants who are infected with HIV have a better prognosis when highly active antiretroviral therapy (HAART) is started early
Prophylaxis for PCP is recommended for infants who may be infected with HIV.
Families will generally be anxious for the results of definitive HIV testing.

14. Laboratory diagnosis of HIV-1 infection during infancy is based on detection of virus or viral nucleic acid. Because infants born to HIV-infected mothers acquire maternal antibodies passively, antibody assays are not informative for diagnosis of infection in children younger than 18 months unless assay results are negative. However, in children 18 months of age and older, HIV antibody assays can be used for diagnosis.
In the United States, the preferred test for diagnosis of HIV infection in infants is the HIV DNA polymerase chain reaction (PCR) assay.
The DNA PCR assay can detect 1 to 10 DNA copies of proviral DNA in peripheral blood mononuclear cells. Approximately 30% to 40% of HIV-infected infants will have a positive HIV DNA PCR assay result in samples obtained before 48 hours of age. A positive result by 48 hours of age suggests in utero transmission. Approximately 93% of infected infants have detectable HIV DNA by 2 weeks of age, and approximately 95% of HIV-infected infants have a positive HIV DNA PCR assay result by 1 month of age. A single HIV DNA PCR assay has a sensitivity of 95% and a specificity of 97% for samples collected from infected children 1 to 36 months of age.

15. HIV isolation by culture is less sensitive, less available, and more expensive than the DNA PCR assay. Definitive results may take up to 28 days. This test no longer is recommended for routine diagnosis.
Detection of the p24 antigen (including immune complex dissociated) is less sensitive than the HIV DNA PCR assay or culture. False-positive test results occur in samples obtained from infants younger than 1 month of age. This test generally should not be used, although newer assays have been reported to have sensitivities similar to HIV DNA PCR assays.
Plasma HIV RNA assays also have been used to diagnose HIV infection. However, a false-negative test result may occur in neonates receiving ARV prophylaxis. Although use of ART can reduce plasma viral loads to undetectable levels, results of DNA PCR assay, which detects cell-associated integrated HIV DNA, remain positive even among people with undetectable viral loads.

16. Viral diagnostic testing in the first few days of life (eg, less than 48 hours of age) is recommended by some experts to allow for early identification of infants with presumed in utero infection. If testing is performed at birth, umbilical cord blood should not be used because of possible contamination with maternal blood.
Obtaining the sample as early as 14 days of age may facilitate decisions about initiating ARV therapy. If found to be infected, infants would be transitioned from neonatal ARV prophylaxis to ARV treatment.
Diagnostic testing with HIV DNA or RNA assays is recommended at
14 to 21 days of age, and if results are negative, repeated at
1 to 2 months of age and again at
4 to 6 months of age.
An infant is considered infected if 2 separate samples test positive by DNA or RNA PCR
In nonbreastfed children younger than 18 months of age with negative HIV virologic test results, presumptive exclusion of HIV infection is based on:
Two negative HIV DNA or RNA virologic test results, from separate specimens, both of which were obtained at 2 weeks of age or older and one of which was obtained at 4 weeks of age or older; OR
One negative HIV DNA or RNA virologic test result from a specimen obtained at 8 weeks of age or older; OR
One negative HIV antibody test result obtained at 6 months of age or older; AND
No other laboratory or clinical evidence of HIV infection (ie, no subsequent positive results from virologic tests if tests were performed and no AIDS-defining condition for which there is no other underlying condition of immunosuppression).
In children with 2 negative HIV DNA PCR test results, many clinicians will confirm the absence of antibody (ie, loss of passively acquired natural antibody) to HIV on testing at 12 through 18 months of age (“seroreversion”). A nonbreastfed infant with 2 antibody-negative blood samples drawn at least 1 month apart and which were both obtained after 6 months of age is considered HIV uninfected.

17. Treatment of the new born
The HIV-negative infant : Zidovudine (Retrovir) prophylaxis is recommended for most infants exposed to HIV in utero to decrease the risk of vertical transmission. Beginning eight hours after birth, these neonates should receive zidovudine in a dosage of 2 mg per kg every six hours for at least six weeks.

18. HIV-positive infant:
The usual age of onset of symptoms is approximately 12 through 18 months of age for untreated infants in the United States who acquired HIV infection through mother-to-child transmission. However, some HIV-infected infants become ill in the first few months of life, whereas others remain relatively asymptomatic for more than 5 years and, rarely, until early adolescence. Without therapy, a bimodal distribution of symptomatic infection has been described: 15% to 20% of untreated HIV-infected children die before 4 years of age, with a median age at death of 11 months (rapid progressors), and 80% to 85% of untreated HIV-infected children have delayed onset of milder symptoms and survive beyond 5 years of age (slow progressors). In the absence of therapy, plasma viral loads among infants who acquired HIV infection through mother-to-child transmission increase rapidly to very high levels (from several hundred thousand to more than 1 million copies/mL) after birth, decreasing only slowly to a “set point” by approximately 2 years of age. This contrasts to infection in adults, in whom a viral load “set point” occurs approximately 6 months after acquisition of infection.

19. Treatment ARV therapy is indicated for most HIV-infected children.
The principal objectives of therapy are to
suppress viral replication maximally,
to restore and preserve immune function,
to reduce HIV-associated morbidity and mortality,
to minimize drug toxicity,
to maintain normal growth and development, and
to improve quality of life.
Initiation of ARV therapy depends on age of the child and on a combination of virologic, immunologic, and clinical criteria. Data from both observational studies and clinical trials indicate that very early initiation of therapy reduces morbidity and mortality compared with starting treatment when clinically symptomatic or immune suppressed. Effective administration of early therapy will maintain the viral load at low or undetectable concentrations and will reduce viral mutation and evolution.

20. Immunization
All recommended childhood immunizations should be given to HIV-exposed infants.
If HIV infection is confirmed, then guidelines for the HIV-infected child should be followed.
Children with HIV infection should be immunized as soon as is age appropriate with inactivated vaccines.
Trivalent inactivated influenza vaccine (TIV) should be given annually according to the most current recommendations.
Additionally, live-virus vaccines (measles-mumps-rubella [MMR] and varicella) can be given to asymptomatic HIV-infected children and adolescents with appropriate CD4+ T-lymphocyte percentages (ie, greater than 15% in children 1 through 5 years of age).
Measles-mumps-rubella-varicella (MMRV) vaccine should not be administered to HIV-infected infants because of lack of safety data in this population.
Rotavirus vaccine may be given to HIV-exposed and HIV-infected infants irrespective of CD4+ T-lymphocyte count.
HIV-infected children should all receive a dose of 23-valent polysaccharide pneumococcal vaccine after 24 months of age, with a minimal interval of 8 weeks since the last conjugate pneumococcal vaccine..

22. Children Who Are HIV Uninfected Residing in the Household of an HIV-Infected Person.
Members of households in which an adult or child has HIV infection can receive MMR vaccine, because these vaccine viruses are not transmitted person to person
To decrease the risk of transmission of influenza to patients with symptomatic HIV infection, all household members 6 months of age or older should receive yearly influenza immunization.
Immunization with varicella vaccine of siblings and susceptible adult caregivers of patients with HIV infection is encouraged to prevent acquisition of wild-type varicella-zoster virus infection, which can cause severe disease in immunocompromised hosts. Transmission of varicella vaccine virus from an immunocompetent host to a household contact is uncommon.

23. Post exposure Passive Immunization of HIV-Infected Children.
Measles HIV-infected children with severe immune suppression who are exposed to measles should receive intramuscular Immune Globulin (IG) prophylaxis (0.5 mL/kg, maximum 15 mL), regardless of immunization status, and exposed, asymptomatic HIV-infected patients also should receive intramuscular IG but at a lower dose (0.25 mL/kg). Children who have received IGIV within 2 weeks of exposure do not require additional passive immunization. Tetanus. HIV-infected children with severe immune suppression who sustain wounds classified as tetanus prone should receive Tetanus Immune Globulin regardless of immunization status. Varicella. HIV-infected children without a history of previous chickenpox or children who have not received 2 doses of varicella vaccine should receive Varicella-Zoster Immune Globulin, if available, within 10 days of close contact with a person who has chickenpox or shingles. Similar post exposure prophylaxis regimens have been recommended for children with moderate to severe immune compromise who previously have been immunized with varicella vaccine. An alternative to Varicella-Zoster Immune Globulin for passive immunization is IGIV, 400 mg/kg, administered once within 10 days after exposure. Children who have received IGIV within 2 weeks of exposure do not require additional passive immunization.

24. references
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