Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
Identification of Perinatal HIV Exposure
Last Updated: April 27, 2017; Last Reviewed: April 27, 2017
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials in children† with clinical outcomes and/or validated endpoints; I* = One or more randomized trials in adults with clinical outcomes and/or validated laboratory endpoints with accompanying data in children† from one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; II = One or more well-designed, nonrandomized trials or observational cohort studies in children† with long-term outcomes; II* = One or more well-designed, nonrandomized trials or observational studies in adults with long-term clinical outcomes with accompanying data in children† from one or more similar nonrandomized trials or cohort studies with clinical outcome data; III = Expert opinion
† Studies that include children or children/adolescents, but not studies limited to post-pubertal adolescents
HIV Testing in Pregnancy
HIV infection should be identified prior to pregnancy or as early in pregnancy as possible. This provides the best opportunity to prevent infant HIV infection and to identify and start therapy as soon as possible in infants who become infected. Universal voluntary HIV testing is recommended as the standard of care for all pregnant women in the United States by The Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV (the Panel), the Centers for Disease Control and Prevention (CDC), the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the U.S. Preventive Services Task Force.1-6 All HIV testing should be performed in a manner consistent with state and local laws (http://nccc.ucsf.edu/clinical-resources/hiv-aids-resources/state-hiv-testing-laws/). CDC recommends the “opt-out” approach, which involves notifying pregnant women that HIV testing will be performed as part of routine care unless they choose not to be tested for HIV. The “opt-out” approach during pregnancy is allowed in every jurisdiction. The "opt-in" approach involves obtaining specific consent before testing and has been associated with lower testing rates.7,8 The mandatory newborn HIV testing approach, adopted by several states, involves testing of newborns for perinatal HIV exposure with or without maternal consent, if prenatal or intrapartum maternal testing is not performed.
Knowledge of antenatal maternal HIV infection enables:
- Women living with HIV to receive appropriate antiretroviral therapy (ART) and prophylaxis against opportunistic infections for their own health, which may also decrease risk of transmission to their partners.2,9,10
- Provision of ART to the mother during pregnancy and labor, and antiretroviral (ARV) drug prophylaxis to the newborn to reduce the risk of perinatal transmission of HIV;4
- Counseling of women living with HIV about the indications for (and potential benefits of) scheduled elective cesarean delivery to reduce perinatal transmission of HIV;4,11-13
- Counseling of women living with HIV about the risks of HIV transmission through breast milk (breastfeeding is not recommended for women with HIV infection living in the United States and other countries where safe alternatives to breast milk are available);14
- Initiation of prophylaxis against Pneumocystis jirovecii pneumonia beginning at age 4 to 6 weeks in all infants with HIV infection and in those infants exposed to HIV whose HIV infection status remains indeterminate;15 and
- Early diagnostic evaluation of infants exposed to HIV, as well as testing of partners and other children, to permit prompt initiation of ART in individuals with HIV infection.1,16,17
Technological improvements have resulted in increased sensitivity to early infection and reduced performance time for laboratory-based assays, allowing completion in less than 1 hour. Accordingly, the Panel now incorporates CDC’s 2014 HIV Laboratory Testing Recommendations.18 The guidelines recommend that HIV testing begin with a fourth-generation immunoassay capable of detecting HIV-1 and HIV-2 antibodies and HIV-1 p24 antigen (called an antigen/antibody combination assay). Individuals with a reactive antigen/antibody combination assay should be tested further with an HIV-1/HIV-2 antibody differentiation assay (supplemental testing). Individuals with a reactive antigen/antibody combination assay and a nonreactive differentiation test should be tested with a Food and Drug Administration-approved HIV nucleic acid test to establish diagnosis of acute HIV infection (http://www.cdc.gov/hiv/pdf/hivtestingalgorithmrecommendation-final.pdf#page=11).
The fourth-generation immunoassay testing for both antigen and antibody is the test of choice and can be done quickly (referred to as expedited), but requires trained laboratory staff and therefore may not be available in some hospitals 24 hours a day. If this test is unavailable, then initial testing should be performed by the most sensitive expedited or rapid test available. Every delivery unit needs to have access to an HIV test that can be done rapidly (<1 hour) 24 hours a day. If positive, testing for confirmation of infection should be done as soon as possible (as with all initial positive assays). Because older tests have lower sensitivity in the context of recent infection, testing following the 2014 CDC algorithm should be considered as soon as feasible if HIV risk cannot be ruled out. Results of maternal HIV testing should be documented in the newborn’s medical record and communicated to the newborn’s primary care provider.
Repeat HIV Testing in the Third Trimester
Repeat HIV testing should be considered for all HIV-seronegative pregnant women. A second HIV test during the third trimester, before 36 weeks’ gestation, is recommended4,19 for women who:
- Are receiving health care in a jurisdiction that has a high incidence of HIV or AIDS in women between ages 15 and 45, or who are receiving health care in facilities in which prenatal screening identifies at least 1 pregnant woman with HIV infection per 1,000 women screened (a list of areas where such screening is recommended is found in the 2006 CDC recommendations; a more up-to-date list is forthcoming);
- Are known to be at high risk of acquiring HIV (e.g., those who are injection drug users or partners of injection drug users, exchange sex for money or drugs, are sex partners of individuals with HIV infection, have had a new or more than one sex partner during the current pregnancy, or have been diagnosed with a new sexually transmitted disease during pregnancy); or
- Have signs or symptoms of acute HIV infection.2,3,20,21
HIV Testing During Labor in Women with Unknown HIV Status
HIV testing is recommended to screen women in labor whose HIV status is undocumented and identify HIV exposure in their infants. HIV testing during labor has been found to be feasible, accurate, timely, and useful both in ensuring prompt initiation of intrapartum and neonatal ARV prophylaxis and in reducing perinatal transmission of HIV (see Intrapartum Care in the Perinatal Guidelines).1-3,5,16
Every hospital offering intrapartum care and every delivery unit must have access to an HIV test that can be performed rapidly (that is, in an expedited fashion with results available within 1 hour) and is available 24 hours a day. Policies and procedures must be in place to ensure that staff are prepared to provide patient education and expedited HIV testing, that appropriate ARV drugs are available whenever needed, and that follow-up procedures are in place for women diagnosed with HIV infection and their infants.
The test of choice is the fourth-generation antigen/antibody combination immunoassay. Because it can be done quickly it is sometimes referred to as “expedited,” but it requires trained lab staff and may not yet be available in hospitals 24 hours a day. If the fourth-generation antigen/antibody combination immunoassay is not available, initial testing should be performed by the most sensitive expedited or rapid test available.
A positive expedited HIV test result must be followed by a supplemental test.18 However, immediate initiation of ARV drug prophylaxis for prevention of perinatal transmission of HIV is recommended pending the supplemental result after an initial positive expedited HIV test.1-6,16 No further testing is required for specimens that are nonreactive (negative) on the initial immunoassay.18
HIV Testing During the Postnatal Period
Women who have not been tested for HIV before or during labor should be offered expedited testing during the immediate postpartum period or their newborns should undergo expedited HIV testing with maternal consent (unless state law allows testing without consent).1,3,4,16 Testing should be done using the fourth-generation antigen/antibody combination immunoassay to screen for established infection and for acute HIV-1 infection; results should be obtained in less than 1 hour. If acute HIV-1 infection is a possibility, then a plasma HIV RNA test should be sent as well. Use of expedited HIV assays for prompt identification of infants exposed to HIV is essential because neonatal ARV prophylaxis should be initiated as soon as possible after birth—ideally no more than 6 to 12 hours after birth—to be effective for the prevention of perinatal transmission. When an initial HIV test is positive in mother or infant, initiation of infant ARV drug prophylaxis and counseling against initiation of breastfeeding is strongly recommended pending results of supplemental HIV tests to confirm and/or differentiate between HIV-1 and HIV-2 infection.4 If supplemental tests are negative and acute HIV infection is excluded, infant ARV drug prophylaxis can be discontinued. In the absence of ongoing maternal HIV exposure, breastfeeding can be initiated. Mechanisms should be developed to facilitate HIV screening for infants who have been abandoned and are in the custody of the state.
Infant HIV Testing when Maternal HIV Test Results are Unavailable
Acute Maternal HIV Infection During Pregnancy or Breastfeeding
The risk of perinatal transmission of HIV is increased in infants born to women who have acute HIV infection during pregnancy or lactation.19,23-26 The fourth-generation antigen/antibody combination immunoassay will detect acute infection more readily than other immunoassays. If acute HIV infection is suspected, and the supplemental test is negative, a plasma HIV RNA test should be sent as well. Women with possible acute HIV infection who are breastfeeding should cease breastfeeding immediately until HIV infection is confirmed or excluded.14 Pumping and temporarily discarding breast milk can be recommended and (if HIV infection is excluded), in the absence of ongoing maternal exposure to HIV, breastfeeding can resume. Care of pregnant or breastfeeding women identified with acute or early HIV infection, and their infants, should follow the recommendations in the Perinatal Guidelines.4
Clinicians should be aware of public health surveillance systems and regulations that may exist in their jurisdictions for reporting infants exposed to HIV; this is in addition to mandatory reporting of persons with HIV infection, including infants. Reporting cases allows for appropriate public health functions to be accomplished.
- American Academy of Pediatrics Committee on Pediatric AIDS. HIV testing and prophylaxis to prevent mother-to-child transmission in the United States. Pediatrics. 2008;122(5):1127-1134. Available at http://www.ncbi.nlm.nih.gov/pubmed/18977995.
- Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006;55(RR-14):1-17; quiz CE11-14. Available at http://www.ncbi.nlm.nih.gov/pubmed/16988643.
- American College of Obstetrics: Gynecology Committee on Obstetric Practice. ACOG Committee Opinion No. 418: Prenatal and perinatal human immunodeficiency virus testing: expanded recommendations. Obstet Gynecol. 2008;112(3):739-742. Available at http://www.ncbi.nlm.nih.gov/pubmed/18757690.
- Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. 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. 2016. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Accessed February 10, 2017.
- Chou R, Cantor AG, Zakher B, Bougatsos C. Screening for HIV in pregnant women: systematic review to update the 2005 U.S. Preventive Services Task Force recommendation. Ann Intern Med. 2012;157(10):719-728. Available at http://www.ncbi.nlm.nih.gov/pubmed/23165663.
- US Preventive Services Task Force. Screening for HIV: recommendation statement. 2013. Available at http://www.uspreventiveservicestaskforce.org/uspstf/uspshivi.htm.
- Boer K, Smit C, van der Flier M, de Wolf F, group Acs. The comparison of the performance of two screening strategies identifying newly-diagnosed HIV during pregnancy. European Journal of Public Health. 2011;21(5):632-637. Available at http://www.ncbi.nlm.nih.gov/pubmed/21051473.
- Yudin MH, Moravac C, Shah RR. Influence of an "opt-out" test strategy and patient factors on human immunodeficiency virus screening in pregnancy. Obstet Gynecol. 2007;110(1):81-86. Available at http://www.ncbi.nlm.nih.gov/pubmed/17601900.
- Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365(6):493-505. Available at http://www.ncbi.nlm.nih.gov/pubmed/21767103.
- Baggaley RF, White RG, Hollingsworth TD, Boily MC. Heterosexual HIV-1 infectiousness and antiretroviral use: systematic review of prospective studies of discordant couples. Epidemiology. 2013;24(1):110-121. Available at http://www.ncbi.nlm.nih.gov/pubmed/23222513.
- Jamieson DJ, Read JS, Kourtis AP, Durant TM, Lampe MA, Dominguez KL. Cesarean delivery for HIV-infected women: recommendations and controversies. Am J Obstet Gynecol. 2007;197(3 Suppl):S96-100. Available at http://www.ncbi.nlm.nih.gov/pubmed/17825656.
- Tubiana R, Le Chenadec J, Rouzioux C, et al. Factors associated with mother-to-child transmission of HIV-1 despite a maternal viral load <500 copies/ml at delivery: a case-control study nested in the French perinatal cohort (EPF-ANRS CO1). Clin Infect Dis. 2010;50(4):585-596. Available at http://www.ncbi.nlm.nih.gov/pubmed/20070234.
- Townsend CL, Cortina-Borja M, Peckham CS, de Ruiter A, Lyall H, Tookey PA. Low rates of mother-to-child transmission of HIV following effective pregnancy interventions in the United Kingdom and Ireland, 2000-2006. AIDS. 2008;22(8):973-981. Available at http://www.ncbi.nlm.nih.gov/pubmed/18453857.
- Committee On Pediatric AIDS. Infant feeding and transmission of human immunodeficiency virus in the United States. Pediatrics. 2013;131(2):391-396. Available at http://www.ncbi.nlm.nih.gov/pubmed/23359577.
- Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children. 2016. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/oi_guidelines_pediatrics.pdf. Accessed February 10, 2017.
- Havens PL, Mofenson LM, American Academy of Pediatrics Committee on Pediatric A. Evaluation and management of the infant exposed to HIV-1 in the United States. Pediatrics. 2009;123(1):175-187. Available at http://www.ncbi.nlm.nih.gov/pubmed/19117880.
- Hegazi A, Forsyth S, Prime K, Group BASI. Testing the children of HIV-infected parents: 6 years on from 'Don't forget the children'. Sex Transm Infect. 2015;91(2):76-77. Available at http://www.ncbi.nlm.nih.gov/pubmed/25316913.
- Centers for Disease Control and Prevention and Association of Public Health Laboratories. Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations. Available at http://stacks.cdc.gov/view/cdc/23447. Published June 27, 2014. Accessed May 22, 2016.
- Birkhead GS, Pulver WP, Warren BL, Hackel S, Rodriguez D, Smith L. Acquiring human immunodeficiency virus during pregnancy and mother-to-child transmission in New York: 2002-2006. Obstet Gynecol. 2010;115(6):1247-1255. Available at http://www.ncbi.nlm.nih.gov/pubmed/20502297.
- Sansom SL, Jamieson DJ, Farnham PG, Bulterys M, Fowler MG. Human immunodeficiency virus retesting during pregnancy: costs and effectiveness in preventing perinatal transmission. Obstet Gynecol. 2003;102(4):782-790. Available at http://www.ncbi.nlm.nih.gov/pubmed/14551009.
- Richey LE, Halperin J. Acute human immunodeficiency virus infection. The American Journal of the Medical Sciences. 2013;345(2):136-142. Available at http://www.ncbi.nlm.nih.gov/pubmed/23095473.
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. 2016. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed February 10, 2017.
- Lockman S, Creek T. Acute maternal HIV infection during pregnancy and breast-feeding: substantial risk to infants. J Infect Dis. 2009;200(5):667-669. Available at http://www.ncbi.nlm.nih.gov/pubmed/19627246.
- Taha TE, James MM, Hoover DR, et al. Association of recent HIV infection and in-utero HIV-1 transmission. AIDS. 2011;25(11):1357-1364. Available at http://www.ncbi.nlm.nih.gov/pubmed/21572305.
- Humphrey JH, Marinda E, Mutasa K, et al. Mother to child transmission of HIV among Zimbabwean women who seroconverted postnatally: prospective cohort study. BMJ. 2010;341:c6580. Available at http://www.ncbi.nlm.nih.gov/pubmed/21177735.
- 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. Available at http://www.ncbi.nlm.nih.gov/pubmed/24586123.