1. CARE OF THE NEONATE

2. August 2012 2 www.aidsetc.org Infants Born to Mothers with Unknown HIV Infection Status (1) Determine possible HIV exposure and need for infant ARV prophylaxis:  Perform rapid HIV test on infant or mother as soon as possible after birth. (AII)  If rapid test result is positive:  Immediately initiate infant ARV prophylaxis (AII)  Do not wait for confirmatory testing  Send confirmatory test (mother or infant)  If negative, stop infant ARV prophylaxis (AIII)  If positive, perform an HIV DNA PCR on the infant (AIII)

3. Infants Born to Mothers with Unknown HIV Infection Status (2)  If infant HIV DNA PCR result is positive:  Discontinue ARV prophylaxis  Promptly refer to an HIV specialist for confirmation of diagnosis and HIV treatment with standard combination ART (AI) August 2012 3 www.aidsetc.org

4. Infant Antiretroviral Prophylaxis (1)  All HIV-exposed infants should receive a 6-week course of ZDV prophylaxis. (AI)  If the mother received standard antepartum and intrapartum ARV prophylaxis with suppressed HIV RNA, risk of HIV transmission is very low; infant ZDV alone is recommended.  If the mother did not receive optimal antepartum and intrapartum prophylaxis, risk of HIV transmission is higher, and additional infant ARVs may be recommended. August 2012 4 www.aidsetc.org

5. Infant Antiretroviral Prophylaxis (2) AgeZidovudine DoseDuration ≥35 weeks’ gestation at birth4 mg/kg/dose PO twice daily If unable to tolerate oral agents: 3 mg/kg/dose IV every 12 hours Birth through 6 weeks Give first dose as close to the time of birth as possible (preferably within 6 to 12 hours) ≥30 to <35 weeks’ gestation2 mg/kg/dose PO every 12 hours or 1.5 mg/kg/dose IV every 12 hours. At age 15 days: increase to 3 mg/kg/dose PO every 12 hours or 2.3 mg/kg/dose IV every 12 hours <30 weeks’ gestation2 mg/kg/dose PO every 12 hours or 1.5 mg/kg/dose IV every 12 hours After age 4 weeks: increase to 3 mg/kg/dose PO every 12 hours or 2.3 mg/kg/dose IV every 12 hours August 2012 5 www.aidsetc.org Dosing for Infant Zidovudine (ZDV) HIV Prophylaxis

6. Infant Antiretroviral Prophylaxis (3)  Infants born to mothers who did not receive antepartum ARV drugs  Standard 6-week course of ZDV, plus  3 doses of NVP in the first week of life (AI)  1st dose at birth  2nd dose 48 hours later  3rd dose 96 hours after 2nd dose  Begin regimen as soon as possible postdelivery August 2012 6 www.aidsetc.org

7. Infant Antiretroviral Prophylaxis (4) Weight BandNevirapine DosageTiming and Duration Birth weight: 1.5-2 kg8 mg TOTAL for each dose 3 doses in the first week of life: 1st dose as soon as possible postdelivery and within 48 hours of birth 2nd dose 48 hours after the 1st dose 3rd dose 96 hours after 2nd dose Birth weight: >2 kg12 mg TOTAL for each dose Same August 2012 7 www.aidsetc.org Weight Band Dosing for Infant Nevirapine (NVP) HIV Prophylaxis

8. Infant Antiretroviral Prophylaxis (5)  For complex scenarios, eg:  Infant born to a mother who received antepartum/ intrapartum ARV drugs but has suboptimal viral suppression at delivery  Infant born to a mother with ARV drug-resistant virus  Consult a pediatric HIV specialist for guidance on combination prophylaxis  Preferably before delivery  Counsel about risks and benefits (BIII) August 2012 8 www.aidsetc.org

9. Infant Antiretroviral Prophylaxis (6)  Management of breast-feeding infants of mothers diagnosed with HIV infection postpartum  Stop breast-feeding  Consult a pediatric HIV specialist  Postexposure prophylaxis vs preemptive therapy  Perform virologic testing in infants <18 months of age  At baseline; 4-6 weeks; 3 months; and 6 months postdiagnosis of maternal infection  HIV DNA PCR is the preferred test for infants receiving combination prophylaxis or preemptive therapy August 2012 9 www.aidsetc.org

10. Infant Antiretroviral Prophylaxis (7) Safety considerations:  Limited data on most ARVs in infants, particularly if given in combination  NRTIs:  ZDV generally safe, may cause transient anemia  3TC + ZDV may increase hematologic toxicity  NVP: Rare cases of severe rash and hepatotoxicity; resistance may occur in infants who become HIV infected  Protease inhibitors not recommended for neonates  No PK data for most  LPV/r: Possible cardiac and other toxicity August 2012 10 www.aidsetc.org

11. Infant Antiretroviral Prophylaxis (8)  In premature infants  Dosing information is available for:  ZDV  NVP  Use of other ARV drugs cannot be recommended because of lack of dosing and safety data. (BIII)  Consult a pediatric HIV specialist for cases in which there is high risk of perinatal transmission in a premature infant. August 2012 11 www.aidsetc.org

12. Infant Antiretroviral Prophylaxis (9) The National Perinatal HIV Hotline 1-888-448-8765 Free clinical consultation on all aspects of perinatal HIV August 2012 12 www.aidsetc.org

13. Initial Postnatal Management of the HIV- Exposed Neonate (1)  Obtain a CBC with differential before initiation of ARV prophylaxis. (BIII)  Frequency of monitoring blood levels is based on: (CIII)  Gestational age and clinical condition of infant  Baseline values  ZDV dosage administered  Receipt of other ARV drugs  Concomitant medications  Maternal ARV regimen August 2012 13 www.aidsetc.org

14. Initial Postnatal Management of the HIV- Exposed Neonate (2)  Intensive monitoring may be considered for infants exposed to combination ARV regimes in utero or neonatally, including: (CIII)  Hematologic monitoring  Serum chemistry  Liver function  Bilirubin levels (ATV exposure)  Monitoring can coincide with timing for HIV diagnostic lab work. (CIII) August 2012 14 www.aidsetc.org

15. Initial Postnatal Management of the HIV- Exposed Neonate (3)  For infants receiving combination ZDV/3TC- containing ARV prophylaxis: (AI)  Recheck hemoglobin and neutrophil count 4 weeks after ARV initiation and/or at the time HIV diagnostic testing is performed.  Consider for infants receiving ZDV 4 mg/kg twice-daily dosing August 2012 15 www.aidsetc.org

16. Initial Postnatal Management of the HIV- Exposed Neonate (4)  Routine measurement of serum lactate is not recommended unless infant develops severe clinical symptoms. (CIII)  Especially neurologic symptoms  In symptomatic infants with significantly abnormal serum lactate levels (>5 mmol/L):  Discontinue ARV prophylaxis  Consult a pediatric HIV specialist for alternative prophylaxis August 2012 16 www.aidsetc.org

17. Initial Postnatal Management of the HIV- Exposed Neonate (5)  If hematological abnormalities are identified, considerations about continuing ARV prophylaxis include: (CIII)  Extent of abnormality  Related symptoms  Duration of prophylaxis  Risk of HIV infection  Availability of alternative interventions  May consider reducing therapy to 4 weeks.  Consult a pediatric HIV specialist. August 2012 17 www.aidsetc.org

18. Initial Postnatal Management of the HIV- Exposed Neonate (6)  Diagnostic HIV tests for infants: (AII)  HIV DNA PCR  Optimal test for diagnosis in the neonatal period  HIV RNA  Standard antibody tests cannot be used to diagnose HIV infection in infants  Detect maternal HIV antibodies up to 18 months August 2012 18 www.aidsetc.org

19. Initial Postnatal Management of the HIV- Exposed Neonate (7)  Virologic tests should be performed at: (AII)  14-21 days,  1 to 2 months, and  4 to 6 months  Virologic tests at birth may be performed  If mother did not have good virologic control during pregnancy  If adequate follow-up cannot be assured August 2012 19 www.aidsetc.org

20. Initial Postnatal Management of the HIV- Exposed Neonate (8)  HIV infection in an infant is diagnosed by two positive virologic tests on separate specimens.  HIV infection is excluded:  Presumptively by two negative virologic tests, one at age ≥14 days and one at age ≥1 month  Definitively (in non-breast-fed infants) by two negative virologic tests, one at age ≥1 month and one at age ≥4 months  Negative status may be confirmed by antibody testing at age 12-18 months  See guidelines for diagnosis of non-subtype-B HIV. August 2012 20 www.aidsetc.org

21. Initial Postnatal Management of the HIV- Exposed Neonate (9)  PCP prophylaxis should begin at age 4-6 weeks, after completion of ARV prophylaxis. (AII)  Unless HIV infection can be presumptively excluded  Evaluate and treat infants as indicated for transmittable maternal coinfections identified through history or physical evaluation.  HIV-exposed infants should follow the routine immunization schedule August 2012 21 www.aidsetc.org

22. Initial Postnatal Management of the HIV- Exposed Neonate (10)  Preventing HIV transmission to infants:  HIV-positive women should not breast-feed  Transmission of HIV in infancy may occur owing to the practice of premasticating foods  Health providers should: (AII)  Inquire about premastication with patients  Instruct HIV-infected caregivers to avoid the practice  Advise on safer feeding options August 2012 22 www.aidsetc.org

23. Long-Term Follow-Up of Infants Exposed to ARVs  Long-term data from infants exposed to ARVs in utero are insufficient.  Children with in utero/neonatal exposure to ARVs who develop significant organ system abnormalities of unknown etiology, particularly the nervous system or heart, should be evaluated or mitochondrial dysfunction. (CIII)  Follow-up of children with exposure should continue to adulthood owing to theoretical concerns for carcinogenicity of nucleoside analogues. (CIII) August 2012 23 www.aidsetc.org