Date of current publication: September 19, 2022
Committee: Perinatal Transmission Prevention Guideline Committee
Date of original publication: August 2020
The Perinatal Transmission Guideline Prevention Committee of the New York State Department of Health (NYSDOH) AIDS Institute (AI) Clinical Guidelines Program recommends that clinicians who provide medical care for infants exposed to HIV follow the Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States > Management of Infants Born to People With HIV Infection published by the U.S. Department of Health and Human Services (DHHS). See the following key topics:
- Antiretroviral Management of Newborns With Perinatal HIV Exposure or HIV Infection
- Diagnosis of HIV Infection in Infants and Children
- Initial Postnatal Management of the Neonate Exposed to HIV
- Long-Term Follow-Up of Infants Exposed to Antiretroviral Drugs
NYS best practices: In addition to supporting the comprehensive DHHS recommendations, this Committee also encourages that care providers in NYS follow the good practices outlined below and in the September 2018 NYSDOH Dear Colleague Letter that addresses intrapartum antiretroviral therapy (ART)/prophylaxis, neonatal antiretroviral (ARV) prophylaxis, and HIV testing of infants and children younger than 24 months.
Note on “experienced” and “expert” HIV care providers: Throughout this guidance, when reference is made to “experienced HIV care provider” or “expert HIV care provider,” those terms are referring to the following 2017 NYSDOH AI definitions:
- Experienced HIV care provider: Practitioners who have been accorded HIV Experienced Provider status by the American Academy of HIV Medicine or have met the HIV Medicine Association’s definition of an experienced provider are eligible for designation as an HIV Experienced Provider in New York State. Nurse practitioners and licensed midwives who provide clinical care to individuals with HIV in collaboration with a physician may be considered HIV Experienced Providers as long as all other practice agreements are met (8 NYCRR 79-5:1; 10 NYCRR 85.36; 8 NYCRR 139-6900). Physician assistants who provide clinical care to individuals with HIV under the supervision of an HIV Specialist physician may also be considered HIV Experienced Providers (10 NYCRR 94.2)
- Expert HIV care provider: A provider with extensive experience in the management of complex patients with HIV.
Newborn HIV Testing in NYS
The NYSDOH strongly advises that all NYS birth facilities use the pediatric HIV testing services at the Wadsworth Center; the services are free of charge for those receiving testing and for NYS clinicians who provide care for HIV-exposed infants.
Early diagnosis of pediatric infection: A nucleic acid test (NAT) to detect HIV RNA or DNA will provide early diagnosis of pediatric HIV infection. Good practice in NYS is to perform an HIV NAT test in an infant at the following ages (see Figure 1, below):
- Within 48 hours of birth
- 2 weeks of age
- 4 to 6 weeks of age
- 8 to 12 weeks of age (see discussion of diagnostic testing within 2 to 6 weeks after completion of ARV prophylaxis, below)
- 4 to 6 months of age
Testing for all HIV-exposed infants within 48 hours of birth: The NYSDOH strongly advises performing an HIV NAT for all known HIV-exposed newborns within the first 48 hours of life. In NYS, from 2010 to 2018, there were 18 documented perinatal transmissions of HIV, and blood specimens were collected within 48 hours of birth among 2,696 exposed infants (72%). Nearly half of infants (44%; n=8) with perinatal transmission had a positive HIV NAT result from the specimen obtained at birth NYSDOH 2020.
Diagnostic testing within 2 to 6 weeks after completion of ARV medications: In 2022, a case of perinatal HIV transmission was identified through HIV NAT at 4 months of age following 3 prior negative NAT results (at birth, 2 weeks of age, and 4 weeks of age) NYSDOH 2022. The newborn was at high risk of perinatal HIV infection and received a 3-drug ARV regimen for presumptive HIV therapy, which was discontinued at 6 weeks of age. The infant was not exposed to HIV through breast milk, and there was no other postnatal HIV exposure risk. It is well documented that results of plasma HIV RNA NATs or plasma HIV RNA/DNA NATs can be affected by ARV drugs administered to newborns as prophylaxis or presumptive HIV therapy DHHS 2021; Patel, et al. 2020; Mazanderani, et al. 2018; Veldsman, et al. 2018; Uprety, et al. 2015.
Confirmatory HIV testing: When a positive HIV NAT result is received for an infant at any age, HIV testing repeated as soon as possible using a new sample is used to confirm a diagnosis of HIV. Two independent positive HIV NAT results provide a definitive diagnosis of HIV infection in exposed infants, and subsequent testing is not necessary.
Two negative HIV NAT results obtained at ≥4 weeks of age and then at ≥4 months of age will confirm that an exposed infant does not have HIV.
For clinical recommendations, see the DHHS guideline section Diagnosis of HIV Infection in Infants and Children.
HIV-2 exposure: Infant exposure to HIV-2 is rare. HIV-2 can be considered if the mother has a reactive HIV antibody screening test result but an unconfirmed diagnosis and HIV-2 has not yet been ruled out with results from an HIV-1/2 antibody differentiation test. If HIV-2 exposure is suspected in the infant, an HIV NAT that detects HIV-2 can be used to rule out or confirm the diagnosis.
For additional clinical recommendations, see the DHHS guideline section Diagnosis of HIV Infection in Infants and Children.
Consultation with an experienced HIV care provider is advised when newborns are exposed to HIV during the perinatal period and especially when there are factors that may increase the risk of transmission. Such factors include but may not be limited to the following: primary or acute HIV during pregnancy, inconsistent adherence to HIV medications, HIV RNA (viral load) ≥50 copies/mL, nonadherence to prenatal visits, undocumented HIV viral load within 4 weeks before delivery, undocumented HIV status at time of delivery, or a preliminary positive HIV test result during labor or shortly after delivery. Expert consultation is also advised if intrapartum ARV prophylaxis was not administered when indicated, when other ARV drugs in addition to zidovudine or early discontinuation of prophylaxis are being considered for the infant, or if the mother has acute or primary HIV while breastfeeding.
|RESOURCES FOR EXPERT CONSULTATION|
Newborn ART and Postnatal Management
ART for newborns: To reduce the risk of perinatal HIV transmission in exposed newborns, appropriate ARV medications, initiated as close to the time of birth as possible, are indicated. The benefit of ART for newborns decreases when initiation is delayed Fiscus, et al. 1999; Wade, et al. 1998. ART should be administered promptly after delivery, preferably within 6 to 12 hours of birth. ARV regimens may be administered to newborns as prophylaxis, presumptive treatment, or as ART when infection is confirmed.
For clinical recommendations, see the DHHS guideline Antiretroviral Management of Newborns With Perinatal HIV Exposure or Perinatal HIV, including Table 8. Newborn Antiretroviral Management According to Risk of HIV Infection in the Newborn and Table 9. Antiretroviral Dosing Recommendations for Newborns.
Initial postnatal management: Educating parents about feeding (i.e., avoidance of breastfeeding and premastication of food), diagnostic testing and medical follow-up, ARV administration, and availability of support services is an essential component of initial postnatal management for infants exposed to HIV. Also essential is emphasizing the need for serial HIV testing for the infant and providing information on the recommended testing schedule and interpretation of results.
The NYSDOH AI recommends that HIV-exposed infants be discharged from care with ARV medications in hand, not just a prescription. Good practice in NYS is to also include the tools needed to administer ARV medications, such as oral syringes. Ensuring that parents are able to administer medication to their newborns is another essential component of discharge planning, as is linkage to care and support services.
Infant feeding: For clinical recommendations, see the DHHS guideline section Infant Feeding for Individuals with HIV in the United States.
Opportunistic Infection Prophylaxis for Newborns
|NEW YORK STATE LAW||
Congenital syphilis: Concomitant sexually transmitted infections (STIs), including syphilis, in individuals with HIV are common. Comprehensive STI screening to identify disease is critical because coinfection increases the risk of adverse perinatal and neonatal outcomes, including likely higher rates of in utero transmission. Infants born to individuals with HIV and concurrent STIs require prompt evaluation to exclude the possibility of transmission of additional infectious agents Adachi(a), et al. 2018.
The NYSDOH recommends that clinicians obtain serologic screening for syphilis for pregnant patients with HIV at the first prenatal visit, during the third trimester (28 to 32 weeks of gestation), and at delivery. No data exist to suggest that infants with congenital syphilis born to individuals with HIV and syphilis require evaluation, therapy, or follow-up for syphilis different than what is recommended for all infants.
Pneumocystis jiroveci pneumonia (previously P. carinii pneumonia; PCP): Initiate PCP prophylaxis at 6 weeks of age for all HIV-exposed infants unless HIV diagnostic testing definitively or presumptively excludes HIV infection; if HIV diagnostic testing results are negative by 5 weeks of age, PCP prophylaxis is not necessary.
Congenital cytomegalovirus: cCMV is the most common intrauterine infection and the leading nongenetic cause of sensorineural hearing loss in children in the United States Grosse, et al. 2017. One in every 200 infants is born with cCMV infection, and approximately 20% of these infants will develop long-term health problems such as hearing or vision loss, intellectual disability, seizures, or developmental delay NYS Senate 2018.
HIV-exposed infants may be at higher risk for acquiring cCMV during pregnancy. Infants with HIV infection, particularly those who acquired HIV in utero, are at greatest risk for cCMV. Screening for cCMV is an important component of a comprehensive evaluation needed for HIV-exposed infants, particularly those born to women not on ART during pregnancy Adachi(b), et al. 2018.
Screening and early diagnosis of cCMV is the NYS standard of care to promote early intervention, monitoring, and medical care that optimizes hearing and developmental outcomes American Academy of Pediatrics 2018; Marsico and Kimberlin 2017; Rawlinson, et al. 2017.
Care providers should discuss with pregnant patients how to reduce the risk of cCMV. cCMV infection is common in children, and the virus can be found in especially high amounts in young children’s saliva and urine. Care providers should inform pregnant patients that they can reduce their risk of cCMV by washing hands after changing diapers and by avoiding sharing food, utensils, or cups with a child.
For clinical recommendations, see the DHHS guideline section Initial Postnatal Management of the Neonate Exposed to HIV.
Adachi(a) K., Xu J., Yeganeh N., et al. Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission. PLoS One 2018;13(1):e0189851. [PMID: 29304083]
Adachi(b) K., Xu J., Ank B., et al. Congenital cytomegalovirus and HIV perinatal transmission. Pediatr Infect Dis J 2018;37(10):1016-21. [PMID: 30216294]
American Academy of Pediatrics. Summaries of infectious diseases: cytomegalovirus infection. Red book: report of the Committee on Infectious Diseases; 2018. https://doi.org/10.1542/9781610021470
DHHS. Recommendations for the use of antiretroviral drugs during pregnancy and interventions to reduce perinatal HIV transmission in the United States. 2021 Dec 30. https://clinicalinfo.hiv.gov/en/guidelines/perinatal/antiretroviral-management-newborns-perinatal-hiv-exposure-or-hiv-infection [accessed 2022 Sep 8]
Fiscus S. A., Schoenbach V. J., Wilfert C. Short courses of zidovudine and perinatal transmission of HIV. N Engl J Med 1999;340(13):1040-43. [PMID: 10189281]
Grosse S. D., Dollard S. C., Kimberlin D. W. Screening for congenital cytomegalovirus after newborn hearing screening: what comes next?. Pediatrics 2017;139(2):e20163837. [PMID: 28119427]
Marsico C., Kimberlin D. W. Congenital cytomegalovirus infection: advances and challenges in diagnosis, prevention and treatment. Ital J Pediatr 2017;43(1):1-8. [PMID: 28416012]
Mazanderani A. H., Moyo F., Kufa T., et al. Brief report: declining baseline viremia and escalating discordant HIV-1 confirmatory results within South Africa's early infant diagnosis program, 2010-2016. J Acquir Immune Defic Syndr 2018;77(2):212-16. [PMID: 29084045]
NYS Senate. Senate Bill S2816: requires urine polymerase chain reaction testing for cytomegalovirus of newborns with hearing impairments. 2018 Oct 2. https://www.nysenate.gov/legislation/bills/2017/s2816/amendment/original [accessed 2022 Sep 8]
NYSDOH. Unpublished data; 2020.
NYSDOH. Unpublished data; 2022.
Patel F., Thurman C., Liberty A., et al. Negative diagnostic PCR tests in school-aged, HIV-infected children on antiretroviral therapy since early life in Johannesburg, South Africa. J Acquir Immune Defic Syndr 2020;83(4):381-89. [PMID: 31913997]
Rawlinson W. D., Boppana S. B., Fowler K. B., et al. Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect Dis 2017;17(6):e177-88. [PMID: 28291720]
Uprety P., Chadwick E. G., Rainwater-Lovett K., et al. Cell-associated HIV-1 DNA and RNA decay dynamics during early combination antiretroviral therapy in HIV-1-infected infants. Clin Infect Dis 2015;61(12):1862-70. [PMID: 26270687]
Veldsman K. A., Maritz J., Isaacs S., et al. Rapid decline of HIV-1 DNA and RNA in infants starting very early antiretroviral therapy may pose a diagnostic challenge. AIDS 2018;32(5):629-34. [PMID: 29334551]
Wade N. A., Birkhead G. S., Warren B. L., et al. Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human immunodeficiency virus. N Engl J Med 1998;339(20):1409-14. [PMID: 9811915]
Updates, Authorship, and Related Guidelines
|Updates, Authorship, and Related Guidelines|
|Date of original publication||August 2020|
|Intended users||NYS clinicians|
|Author and writing group conflict of interest disclosures||There are no author or writing group conflict of interest disclosures|
|Developer and funder|
See Guideline Development and Recommendation Ratings Scheme, below.
Guideline Development and Recommendation Ratings
|Guideline Development: New York State Department of Health AIDS Institute Clinical Guidelines Program|
|Program manager||Clinical Guidelines Program, Johns Hopkins University School of Medicine, Division of Infectious Diseases. See Program Leadership and Staff.|
|Mission||To produce and disseminate evidence-based, state-of-the-art clinical practice guidelines that establish uniform standards of care for practitioners who provide prevention or treatment of HIV, viral hepatitis, other sexually transmitted infections, and substance use disorders for adults throughout New York State in the wide array of settings in which those services are delivered.|
|Expert committees||The NYSDOH AI Medical Director invites and appoints committees of clinical and public health experts from throughout New York State to ensure that the guidelines are practical, immediately applicable, and meet the needs of care providers and stakeholders in all major regions of New York State, all relevant clinical practice settings, key New York State agencies, and community service organizations.|
|Disclosure and management of conflicts of interest||
|Evidence collection and review||
|Review and approval process||
|Recommendation Ratings Scheme|
|Strength||Quality of Evidence|
|A||Strong||1||Based on published results of at least 1 randomized clinical trial with clinical outcomes or validated laboratory endpoints.|
|B||Moderate||*||Based on either a self-evident conclusion; conclusive, published, in vitro data; or well-established practice that cannot be tested because ethics would preclude a clinical trial.|
|C||Optional||2||Based on published results of at least 1 well-designed, nonrandomized clinical trial or observational cohort study with long-term clinical outcomes.|
|2†||Extrapolated from published results of well-designed studies (including nonrandomized clinical trials) conducted in populations other than those specifically addressed by a recommendation. The source(s) of the extrapolated evidence and the rationale for the extrapolation are provided in the guideline text. One example would be results of studies conducted predominantly in a subpopulation (e.g., one gender) that the committee determines to be generalizable to the population under consideration in the guideline.|
|3||Based on committee expert opinion, with rationale provided in the guideline text.|