HIV in pregnancy: Identification of intrapartum and perinatal HIV exposures
Posted: Feb 15 2019
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Dorothy L. Moore, Upton D. Allen MBBS; Canadian Paediatric Society, Infectious Diseases and Immunization Committee
Paediatr Child Health 2019(1):42–45.
The benefits of human immunodeficiency virus (HIV) testing in pregnancy, when combined with appropriate maternal antiretroviral therapy and intrapartum and postnatal prophylaxis, are well established. The vertical rate of transmission of HIV in North America is now well below 2%. Efforts must continue to ensure that these benefits are sustained. Women who have received little or no prenatal care and those who present for delivery with unknown HIV status need immediate testing. As more infants are exposed to antiretroviral agents, strategies need to be implemented to ensure adequate follow-up of these infants. Issues relating to the identification of HIV-exposed infants are highlighted.
Keywords: Human immunodeficiency virus; Infant; Intrapartum transmission; Pregnancy; Screening
This statement replaces the 2008 Canadian Paediatric Society (CPS) statement on human immunodeficiency virus (HIV) testing in pregnancy . The primary focus is on identification of newborns with perinatal exposure to HIV. Clinicians should also consult current Canadian guidelines on the management of HIV-infected pregnant women .
Implementing a strategy to reduce perinatal HIV transmission requires two steps. The first step is to identify women who have been infected with HIV. The second step involves access to collaborative, coordinated HIV care by knowledgeable health care providers for pregnant women, mothers, and newborns. This care includes antepartum combination antiretroviral therapy, intrapartum antiretroviral therapy, postnatal antiretroviral therapy, and exclusive formula feeding of infants born to infected mothers . To date, such efforts have led to a dramatic decline in the rates of HIV-infected newborns in North America, along with improved care for women infected with HIV –. To facilitate appropriate care and ensure that medications used during delivery and for the newborn are as up-to-date as possible, consultation with a paediatric infectious disease specialist is advised.
Current vertical transmissions rates in Canada are less than 2% . When no interventions are undertaken during pregnancy, delivery or the neonatal period, perinatal HIV transmission rates can be as high as 25% . Risk factors for that scenario include pregnant women with:
Late or no prenatal care, injection drug use, recent illness suggestive of HIV seroconversion, regular unprotected sex with a partner known to be living with HIV (or with significant risk for HIV infection), diagnosis of sexually transmitted infections during pregnancy, emigration from an HIV-endemic area or recent incarceration.
Some transmissions occur in utero but the majority occur at the time of delivery, with additional risk for infection if the newborn is breastfed. Risk of transmission is especially high when the mother has acute or early untreated infection –. The earlier an HIV diagnosis is made in a pregnant woman, the better the chances of optimizing her own health , preventing vertical transmission, and reducing risk for spread to her sexual partners. Perinatal transmission is now rare in Canada, but it still happens. Women who have received little or no prenatal care are especially at risk.
While the benefits of HIV testing in pregnancy have been profound, there are serious, ongoing personal, familial, and societal stresses for women who learn they are HIV-positive . To ensure informed decision-making, access to experts in the management of HIV infection in women and newborns is essential.
While the number of HIV-infected newborns has declined in North America since the implementation of HIV testing in pregnancy, there is a related rise in the number of infants exposed to antiretroviral agents in utero . Toxicity caused by in-utero exposure to antiretroviral agents is a potential complication –. Current evidence supports the benefits of prophylaxis outweighing the potential risks of drug toxicity –. In the short term, significant toxicity is rare, but information concerning the long-term effects of intrauterine exposure to antiretroviral agents is minimal at present. The need for ongoing surveillance and data collection is well recognized. Long-term outcomes of concern include neurodevelopmental and learning problems. Beyond the potential risk of exposure to antiretroviral agents, ongoing studies of the effects of maternal HIV infection on the immune system of uninfected infants are underway –.
Detailed information about HIV tests is available , including resources for patients . The standard approach to diagnosing HIV infection during pregnancy in Canada is by multistep serology testing. The first step is a screening test for HIV antibodies using an enzyme immunoassay. If the enzyme immunoassay is reactive, the sample is re-tested using a more specific confirmatory test for HIV antibodies (e.g., Western blot). Rapid HIV antibody testing is defined as a screening test that provides a result in less than 30 minutes. Findings must be confirmed by standard serology. HIV nucleic acid amplification assays (DNA or RNA polymerase chain reaction (PCR)) are used to identify infection in infants and to quantify HIV viral load. HIV antigen/antibody combination tests may be used to identify very recent infection during pregnancy, or in the mother following delivery.
With respect to the identification of newborns with perinatal exposure to HIV, there is incontrovertible evidence that transmission of HIV from mother to child can be reduced and virtually eliminated through HIV testing during pregnancy, appropriate perinatal antiretroviral therapy, reducing HIV exposure during delivery, and avoiding breastfeeding. In this context, the CPS supports current Canadian  and American  recommendations:
- HIV testing early in pregnancy is recommended as the standard of care in Canada for all pregnant women – (AII) (See Table 1).
- Repeat testing throughout pregnancy is recommended for all who are HIV-seronegative on initial testing but who are known to be at high risk for HIV acquisition. Repeat testing in the third trimester (ideally before 36 weeks gestation) should also be considered for other HIV-seronegative women when their ongoing risk of acquiring HIV is unclear (AIII).
- Health care providers caring for pregnant women who are identified as being HIV-positive should consult with specialists with expertise in managing HIV in pregnancy for advice on counselling about prevention of transmission to the infant and to sexual partners, appropriate antiretroviral therapy, optimal follow-up during pregnancy, and intrapartum and postnatal prophylaxis (AIII).
- Physicians must ensure that the HIV status of a pregnant woman in their care is conveyed to the team who will be caring for her at delivery. Failure to share this information increases risk for neonatal HIV acquisition and may result in unnecessary exposure of the newborn to antiretrovirals.
- Women who present in labour with undocumented HIV status should undergo rapid HIV testing at the time of labour or delivery. If results are positive, intrapartum and infant postnatal antiretroviral prophylaxis  should be initiated immediately, pending results of the confirmatory HIV antibody test (AII). Health care providers are advised to consult urgently with a paediatric infectious diseases specialist because the preferred antiretroviral regimens are evolving. A list of paediatric infectious diseases specialists with expertise in caring for infants exposed to or infected with HIV may be found on the Canadian Pediatric & Perinatal HIV/AIDS Research Group website: www.cparg.ca/.
- Women who have not been tested for HIV before or during labour should undergo rapid HIV antibody testing in the immediate postpartum period. If they are not available for or refuse testing, their newborns must undergo rapid HIV antibody testing (AIII). If a parent refuses permission to have the infant tested, child protection authorities may need to be notified.
- If test results are positive for mother or infant, infant antiretroviral prophylaxis  should be initiated immediately and no later than 72 hours post-delivery. Breastfeeding should be deferred until the confirmatory HIV antibody test result is available and proves negative (AII).
- If rapid HIV antibody testing is unavailable and there is concern that the mother is at high risk for HIV infection, starting newborn antiretroviral prophylaxis pending test results should be considered (BIII).
- When a mother or newborn tests positive for HIV antibody, identifying exposure, the infant should be tested immediately for infection by HIV DNA or RNA polymerase chain reaction (PCR), within 48 hours of birth if possible. If this test is positive, prophylaxis should be stopped and antiretroviral treatment initiated in consultation with a paediatric infectious diseases specialist (AIII).
- For HIV-seronegative women in whom acute HIV infection is suspected during pregnancy, intrapartum or while breastfeeding, a virologic test (e.g., HIV RNA PCR, or antigen test) should be performed as soon as possible because antibody tests may be negative early in HIV infection (AII).
- Results of maternal and infant HIV testing should be documented in the newborn’s medical record and communicated to the newborn’s primary care provider (AIII).
- If HIV infection was initially diagnosed in the mother during or after delivery, arrangements should be made for her appropriate follow-up and ongoing care.
- Health care providers should monitor both the short-term effects (e.g., anemia, neutropenia) and long-term outcomes (general health, growth, and neurodevelopment) of infants who have been exposed to HIV infection or antiretroviral agents (AIII).
- HIV antibody testing is recommended for infants in foster care and for adoptees whose birth mother’s HIV infection status is not known (AIII).
This revised position statement has been reviewed by the Fetus and Newborn and Community Paediatrics Committees of the Canadian Paediatric Society. It was also reviewed, with our best thanks, by members of the Society of Obstetricians and Gynaecologists of Canada’s Clinical Obstetrics Committee and Infectious Disease Committee, and by representatives from the College of Family Physicians of Canada’s Maternity and Newborn Care Program Committee.
CANADIAN PAEDIATRIC SOCIETY INFECTIOUS DISEASES AND IMMUNIZATION COMMITTEE
Members: Michelle Barton-Forbes MD; Sean Bitnun MD; Natalie A Bridger MD (past member); Shalini Desai MD (past member); Michael Forrester MD (resident member); Ruth Grimes MD (Board Representative); Nicole Le Saux MD (Chair); Laura Sauve MD; Karina Top MD
Liaisons: Upton D. Allen MBBS, Canadian Pediatric & Perinatal HIV/AIDS Research Group; Tobey Audcent MD, Committee to Advise on Tropical Medicine and Travel (CATMAT), Public Health Agency of Canada; Carrie Byington MD, Yvonne Maldonado MD, Committee on Infectious Diseases, American Academy of Pediatrics; Marc Lebel MD, IMPACT (Immunization Monitoring Program, ACTIVE); Jane McDonald MD, Association of Medical Microbiology and Infectious Disease Canada; Dorothy L. Moore MD, National Advisory Committee on Immunization (NACI); Howard Njoo MD, Public Health Agency of Canada
Consultant: Noni E. MacDonald MD
Principal authors: Dorothy L. Moore MD, Upton D. Allen MBBS
- Robinson JL; Canadian Paediatric Society, Infectious Diseases and Immunization Committee. Testing for HIV infection in pregnancy. Paediatr Child Health 2008;13(3):221–4.
- Society of Obstetricians and Gynaecologists of Canada. Guidelines for the care of pregnant women living with HIV and interventions to reduce perinatal transmission. J Obstet Gynaecol Can 2014; 36(8):721–34.
- Bitnun A, Brophy J, Samson L, et al. Prevention of vertical HIV transmission and management of the HIV-exposed infant in Canada in 2014. Can J Infect Dis Med Microbiol 2014;25(2):75–7.
- AIDSinfo. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. https://aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf. Last update May 30, 2018. (Accessed August 14, 2018).
- Lockman S, Creek T. Acute maternal HIV infection during pregnancy and breast-feeding: Substantial risk to infants. J Infect Dis 2009;200(5):667–9.
- Humphrey JH, Marinda E, Mutasa K, et al.; ZVITAMBO Study Group. Mother to child transmission of HIV among Zimbabwean women who seroconverted postnatally: Prospective cohort study. BMJ 2010;341:c6580.
- Taha TE, James MM, Hoover DR, et al. Association of recent HIV infection and in-utero HIV-1 transmission. AIDS 2011;25(11):1357–64.
- Drake AL, Wagner A, Richardson B, John-Stewart G. Incident HIV during pregnancy and postpartum and risk of mother-to-child HIV transmission: A systematic review and meta-analysis. PLoS Med 2014;11(2):e1001608.
- Koenig LJ, Moore J. Women, violence, and HIV: A critical evaluation with implications for HIV services. Matern Child Health J 2000;4(2):103–9.
- Mofenson LM, Watts DH. Safety of pediatric HIV elimination: The growing population of HIV- and antiretroviral-exposed but uninfected infants. PloS Med 2014;11(4):e1001636.
- Blanche S, Tardieu M, Rustin P, et al. Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues. Lancet 1999;354(9184):1084–9.
- Jao J, Abrams EJ. Metabolic complications of in utero maternal HIV and antiretroviral exposure in HIV-exposed infants. Pediatr Infect Dis J 2014;33(7):734–40.
- Brogly SB, Ylitalo N, Mofenson LM, et al. In utero nucleoside reverse transcriptase inhibitor exposure and signs of possible mitochondrial dysfunction in HIV-uninfected children. AIDS 2007;21(8):929–38.
- Barret B, Tardieu M, Rustin P, et al.; French Perinatal Cohort Study Group. Persistent mitochondrial dysfunction in HIV-1-exposed but uninfected infants: Clinical screening in a large prospective cohort. AIDS 2003;17(12):1769–85.
- Côté HC, Raboud J, Bitnun A, et al. Perinatal exposure to antiretroviral therapy is associated with increased blood mitochondrial DNA levels and decreased mitochondrial gene expression in infants. J Infect Dis 2008;198(6):851–9.
- The Perinatal Safety Review Working Group. Nucleoside exposure in the children of HIV-infected women receiving antiretroviral drugs: Absence of clear evidence for mitochondrial disease in children who died before 5 years of age in five United States cohorts. J Acquir Immune Defic Syndr 2000;25(3):261–8.
- Lipshultz SE, Easley KA, Orav EJ, et al. Absence of cardiac toxicity of zidovudine in infants. Pediatric pulmonary and cardiac complications of vertically transmitted HIV infection study group. N Engl J Med 2000;343(11):759–66.
- Alimenti A, Forbes JC, Oberlander TF, et al. A prospective controlled study of neurodevelopment in HIV-uninfected children exposed to combination antiretroviral drugs in pregnancy. Pediatrics 2006;118(4):e1139–45.
- Kakkar F, Lamarre V, Ducruet T, et al. Impact of maternal HIV-1 viremia on lymphocyte subsets among HIV-exposed uninfected infants: Protective mechanism or immunodeficiency. BMC Infect Dis 2014;14:236.
- Taron-Brocard C, Le Chenadec J, Faye A, et al.; France REcherche Nord&Sud Sida-HIV Hepatites – Enquete Perinatale Francaise – CO1/CO11 Study Group. Increased risk of serious bacterial infections due to maternal immunosuppression in HIV-exposed uninfected infants in a European country. Clin Infect Dis 2014;59(9):1332–45.
- Kidzeru EB, Hesseling AC, Passmore JA, et al. In-utero exposure to maternal HIV infection alters T-cell immune responses to vaccination in HIV-uninfected infants. AIDS 2014;28(10):1421–30.
- AIDS Bureau, Ontario. Guidelines for HIV Testing and Counselling, March 2008. http://www.ohsutp.ca/uploads/Ontario_HIV_Testing_guidelines.pdf (Accessed August 14, 2018).
- Public Health Agency of Canada. Human Immunodeficiency Virus – HIV screening and testing guide. https://www.canada.ca/en/public-health/services/hiv-aids/hivscreening-testing-guide.html (Accessed August 14, 2018).
- Canadian AIDS Society. What is HIV testing and why does it matter? http://www.cdnaids.ca/hiv-testing/ (Accessed August 14, 2018).
- U.S. Department of Health and Human Services. HIV overview/HIV testing. https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/47/hiv-testing (Accessed September 12, 2018).
Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.