1. Newborn born TO hiv(+) mother
ID weekly conferences
Gouri Scheurmann
Pediatric Resident PGY 1

2. History and physical
Patient M is a newborn ex-40 5/7 weeks gestational age, born via spontaneous vaginal delivery.
Mother: 36 y/o; Gravidity/Parity G5 T3 P0 A1 L3; received prenatal care.
Prenatal labs: Blood Type O+, negative Antibody Screen;  Rubella: Immune; RPR Negative;  Hepatitis B Surface Antigen: Negative; HIV positive; Group B Strep positive.
Mother presented at 9 cm of dilation, AROM at delivery.
Mother did not receive antepartum or intrapartum zidovudine
Length of labor was around 12 hours.
Baby was born AGA, Apgar 9/9, meconium-stained amniotic fluid.
Baby received an infusion of zidovudine

3. Perinatal history
Mother is originally from Congo, French speaking She has lived in the US for the last 5 years.
Has a history of HIV, not compliant with medications.
Prior to and during pregnancy, mother was on Prezista (darunavir), Truvada (emtricitabine-tenofovir), and Norvir (ritonavir). HIV susceptibility testing not available in PowerChart
On October 4, 2017 patient’s viral load was 35,160. In November 2017 she had a viral load of 143 and T cell count of 373. Her pregnancy was managed at Niagara Hospital
She had 2 prior vaginal deliveries followed by one C-section
-Reason for the later C-section was HIV

4. Physical exam
T: 37.0  °C  (Axillary)  HR: 160 (Apical)  RR: 60  WT: 3.580 kg (52%tile) Length: 52cm (66%tile) Head circumference: 36.5cm (86%tile)
Head: Normocephalic, anterior fontanelle open, soft, and flat, open sutures, normal facies Nose: Normal Ears: normal, no pits or tags noted Mouth: oral mucosa pink and moist, palate intact, tongue moves forward the gumline Neck: supple
Chest: no deformities, no clavicular fractures noted Respirations: clear to auscultation bilaterally, good aeration, normal WOB Heart: S1/S2, regular rate and rhythm, no murmur appreciated Pulses: 2+ femoral pulses bilaterally, brisk cap refill
Abdomen: soft, nondistended, nontender, normoactive bowel sounds, no organomegaly Umbilical Cord: normal umbilical stump, 3 vessel cord with no erythema or discharge
Genitalia: normal external genitalia, patent anus, Tanner 1 female Extremities: no deformities, good muscle tone Hips: no clicks or clunks appreciated
Spine: no sacral dimple, no tufts of hair Reflexes:  normal grasp reflex present, normal gallant reflex, normal sucking reflex
Skin: pink, dry, well-perfused, mongolian spots on the sacral region, multiples brown macules of 0.5cm with irregular borders on the torso along the spinal column

5. Assessment
This is a 40+ 5/7 weeks AGA infant born to a 36 y/o G5P3 GBS positive mother who is HIV positive. Infant was delivered vaginally with APGARs of 9 and 9. Infant is admitted to the newborn nursery for routine newborn care and management of HIV exposure.

6. Thoughts, questions?

7. Hospital course Maternal course:
Did not receive antepartum or intrapartum ART drugs
Non compliant with ART until late in pregnancy
Had detectable HIV viral load close to the time of delivery
Received combination ART and did not have sustained viral suppression
Baby was delivered vaginally

8. Hospital Course Patient was seen at 1hrs of life by the ID team
Recommendations from our team were:
Avoid breast feeding
Obtain HIV viral load on the mother ASAP (request expedited testing from state reference laboratory).
Obtain HIV PCR from the baby, as well as CBC with diff
Start triple ART as follows:     3TC 2mg/kg per dose PO BID for at least 6 weeks     ZDV 4mg/kg/dose PO BID for at least 6 weeks     NVT 6mg/kg/dose PO BID for at least 6 weeks
Patient will also need repeat HIV PCR as follows:     14 to 21 days at the Pediatric ID clinic     1-2 months     4 to 6 months
Follow up HIV PCR results for baby and mother.
This suggestions was at 1hr of live

9. hospital COURSE Newborn course: Hepatitis B vaccine was given
Baby was started immediately on triple ART
On the second day of life HIV PCR was sent for the baby
The mother’s viral load at delivery was [pending]
CBC was unremarkable except for a low MCV for which Bart’s hemoglobin was sent
NB screening test: hearing test pass bilaterally/CCHD pass
Baby was discharged home at 3 days old:
Patient will follow up with HIV clinic in TG
Follow up set up with ID clinic 2 weeks after discharge

10. Intrapartum Care
Antiretroviral therapy (ART) regimens are now recommended for all pregnant women regardless of CD4 T lymphocyte (CD4) cell count and HIV viral load for treatment of HIV and prevention of perinatal transmission of HIV; t

11. Intrapartum Care Intravenous (IV) zidovudine:
Should be administered to women living with HIV with HIV RNA >1,000 copies/mL
May be considered for women with HIV RNA between 50 and 999 copies/mL.
Scheduled cesarean delivery at 38 weeks’ gestation is recommended for women who have HIV RNA >1,000 copies/mL near delivery .
Women who present in labor with unknown HIV status should undergo expedited antigen/antibody HIV testing.
If the results are positive, an HIV-1/HIV-2 antibody differentiation test and an HIV-1 RNA assay should be done and maternal (IV zidovudine)/infant (combination antiretroviral [ARV] prophylaxis) ARV drugs should be initiated.
-Zidovudine: However, some experts would administer IV zidovudine to women with RNA levels in this range, as the transmission risk is slightly higher when HIV RNA is in the range of 50 and 999 copies/mL compared to <50 copies/mL. In women with HIV RNA >1,000 copies/mL undergoing a scheduled cesarean delivery for prevention of transmission, IV zidovudine administration should begin 3 hours before the scheduled operative delivery. If zidovudine was not used in the antenatal ART regimen because of known or suspected zidovudine resistance, intrapartum use of the drug is still recommended in women with HIV RNA >1,000 copies/mL near delivery,

12. Diagnosis of HIV Infection in Infants and Children
RNA or DNA polymerase chain reaction (PCR)
Virologic diagnostic testing is recommended for all infants with perinatal HIV exposure at the following ages:
14 to 21 days
1 to 2 months
4 to 6 months
Additional virologic diagnostic testing at birth should be considered for infants at higher risk of perinatal HIV transmission and at 2 to 4 weeks after cessation of antiretroviral prophylaxis.
Antigen/antibody combination immunoassays the sensitivity of the antigen component in the first months is low, and antibody tests should not be used for diagnosis in infants and children less than 18 months of age.
Children with perinatal HIV exposure aged 18 to 24 months occasionally have residual maternal HIV antibodies; HIV NAT is preferred
Antibody tests, including the newer antigen-antibody combination immunoassay, do not establish the presence of HIV infection in infants because of transplacental transfer of maternal antibodies to HIV
Antigen/antibody combination immunoassays which detect HIV-1/2 antibodies as well as HIV-1 p24 antigen are not recommended for infant diagnosis
ARV prophylaxis, particularly combination ARV prophylaxis, may reduce the sensitivity of testing during prophylaxis

13. Diagnosis of HIV Infection in Infants and Children
A positive virologic test should be confirmed as soon as possible by a repeat virologic test on a second specimen.
Definitive exclusion of HIV infection is based on 2 or more negative virologic tests, with 1 obtained at age ≥1 month and 1 at age ≥4 months, or 2 negative HIV antibody tests from separate specimens obtained at age ≥6 months.
Presumptively excluded in non-breastfed infants with two or more negative virologic tests (one at age ≥14 days and one at age ≥4 weeks) or one negative virologic test at age ≥8 weeks, or one negative HIV antibody test at age ≥6 months.
Diagnosis in children aged >24 months relies primarily on HIV antibody and antigen/antibody tests
Diagnostic testing in children with non-perinatal exposure only or children with perinatal exposure aged >24 months relies primarily on the use of HIV antibody (or antigen/antibody) tests.
For both presumptive and definitive exclusion of HIV infection, a child must have no other laboratory (i.e., no positive virologic test results or low CD4 T lymphocyte [CD4] cell count/percent) or clinical evidence of HIV infection and not be breastfeeding

14. Diagnosis of HIV Infection in Infants and Children
Low Risk: Infants born to mothers who received standard ART during pregnancy with sustained viral suppression
Higher Risk: Infants born to mothers living with HIV who did not receive prenatal care, did not receive antepartum or intrapartum ARVs, received intrapartum ARV drugs only, mothers who initiated ART late in pregnancy (late second or third trimester), were diagnosed with acute HIV infection during pregnancy, who had detectable HIV viral loads close to the time of delivery, including those who received combination ARV drugs and did not have sustained viral suppression.
NAT: nucleic acid testing
For higher-risk infants, additional virologic diagnostic testing should be considered at birth and 2 to 4 weeks after cessation of ARV prophylaxis

15. Virologic Testing at Birth for Newborns at Higher Risk of Perinatal HIV Transmission
Infants who have a positive virologic test at or before age 48 hours are considered to have early (i.e., intrauterine) infection.
Infants who have a negative virologic test during the first week of life and subsequent positive tests are considered to have late (i.e., intrapartum) infection.

16. Management of newborns with PERINATAL exposure to HIV
ID weekly conferences
Andrew Seier
Medical Student MS-4

17. Antepartum Zidovudine
Continue ART on schedule during labor and before scheduled caesarean delivery.
Viral load >1000 copies/mL?
IV zidovudine
Scheduled caesarean at 38 weeks if possible
YES NO
Viral load >50 and <1000?
Limited data. Slightly higher transmission risk, consider IV zidovudine.
YES NO
IV zidovudine not required
VIRAL LOAD <50

18. In labor with unknown HIV status
STAT HIV antigen/antibody testing
Positive result
HIV-1/HIV-2 Ab differentiation test
Start infant on ARV drugs pending results
Exclude with negative HIV RNA test
Stop ARV drugs, avoid breastfeeding until definitive results are available
NEGATIVE
POSITIVE, or ACUTE INFECTION
Continue ARV drugs for infant

19. Other intrapartum considerations
In women with viral load >1,000 copies/mL or unknown viral load who present in spontaneous labor or with ruptured membranes, there is insufficient evidence to determine whether cesarean reduces the risk of perinatal HIV transmission. Management of women originally scheduled for cesarean delivery because of HIV infection who present in labor must be individualized at the time of presentation.
AROM performed in the setting of ART with virologic suppression is not associated with increased risk of perinatal transmission and can be performed for standard obstetric indications
The following should generally be avoided because of a potential increased risk of transmission, unless there are clear obstetric indications:
AROM in the setting of viremia
Routine use of fetal scalp electrodes for fetal monitoring
Operative delivery with forceps or a vacuum extractor

20. Definitions
ARV Prophylaxis: The administration of one or more ARV drugs to a newborn without confirmed HIV infection to reduce the risk of HIV acquisition
Empiric HIV Therapy: The administration of a three-drug combination ARV regimen to newborns at highest risk of HIV acquisition
Intended to be preliminary treatment for a newborn who is later confirmed to have HIV
Also serves as prophylaxis against HIV acquisition for those newborns who are exposed to HIV in utero, during the birthing process or during breastfeeding and who do not acquire HIV.
HIV Therapy: The administration of a three-drug combination ARV regimen at treatment dosages to newborns with confirmed HIV infection

21. Scenarios
Mother was compliant with ART during pregnancy and had sustained viral suppression near delivery
4-week zidovudine ARV prophylaxis
Unknown maternal HIV status with positive expedited antibody/antigen testing
ARV prophylaxis or empiric therapy
Based on assessment of risk
Has not received antepartum or intrapartum ARV drugs, only received intrapartum ARV drugs, did not achieve viral suppression near delivery, or had primary or acute HIV infection during pregnancy or breastfeeding.
ARV prophylaxis or empiric therapy
Based on assessment of risk

22. Neonatal ARV Management
ARV Regimens
Category
Description
Neonatal ARV Management
Low Risk of Perinatal HIV Transmission
Mothers compliant with ART during pregnancy with sustained viral suppression near delivery
4 weeks of ZDV
Higher Risk of Perinatal HIV Transmission
Mothers who received neither antepartum nor intrapartum, or only intrapartum ARV drugs
Mothers who received ARV drugs but who have detectable viral load near delivery Mothers with acute or primary HIV infection during pregnancy or breastfeeding
Combination ARV prophylaxis with 6 weeks ZDV and 3 doses of NVP (prophylaxis dosage, with doses given within 48 hours of birth, 48 hours after first dose, and 96 hours after second dose)  OR Empiric HIV therapy consisting of ZDV, 3TC, and NVP (treatment dosage)
Presumed Newborn HIV Exposure
Mothers with unknown HIV status who test positive at delivery or postpartum or whose newborns have a positive HIV antibody test
ARV management as above (for higher risk of perinatal HIV transmission). ARV management should be discontinued immediately if supplemental testing confirms that mother does not have HIV.
Newborn with Confirmed HIV
Confirmed positive newborn HIV virologic test/NAT
3 drug combination ARV regimen at treatment dosage

23. The cutting edge

24. Study Criteria Criteria Inclusion Criteria: COHORT 1 MOTHERS
Presumed or confirmed HIV infection (if presumed, must be confirmed within 7 days after study entry)
No receipt of ARVs during the current pregnancy.
Willing and able to provide written informed consent for maternal and infant study participation
COHORT 1 INFANTS
≤ 48 hours of age
≥ 34 weeks gestational age at birth
Able to take ARVs by mouth, nasogastric tube, or gastrostomy tube

25. Study Criteria (cont.) COHORT 2 MOTHERS COHORT 2 INFANTS
Presumed or confirmed HIV infection (if presumed, must be confirmed within 7 days after study entry)
Willing and able to provide written informed consent for maternal and infant study participation
COHORT 2 INFANTS
≤ 10 days of age
≥ 34 weeks gestational age at birth
≥ one nucleic acid test positive for HIV infection on a sample drawn within 48 hours of birth
Started ART within 48 hours of birth on a regimen including 2 NRTIs plus NVP at a dose of at least 8 mg/day for infants weighing ≤ 2 kg or 12 mg/day for infants > 2 kg AND/OR LPV/r
ART regimen was taken daily from date of initiation until study entry
Able to take ARVs by mouth, nasogastric tube, or gastrostomy tube
Exclusion Criteria, INFANTS: Any clinically significant diseases (other than HIV infection) or clinically significant findings during review of medical history or physical examination prior to entry that, in the investigator's opinion, would interfere with study participation or interpretation.

26. Study Protocol ARV
2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs): determined by the primary provider and dosed by WHO or individual country guidelines
Nevirapine (NVP)
6 mg/kg bid: Step 1 through Step 2 Week 4
200 mg/m2 bid (or WHO weight band dosing): beginning at Step 2 Week 4
If HIV infection is confirmed: Lopinavir (LPV) 300mg/m2 + ritonavir (RTV) 75 mg/m2 bid (LPV/r) are added when the infant reaches ≥ 14 days of age AND ≥ 42 weeks postmenstrual age
Evaluation for ART cessation at week 84, follow off ART until age 5 years

27. Discussion