Maternal HIV Testing and Identification of Perinatal HIV Exposure

HIV infection should be identified before pregnancy (see Prepregnancy Counseling and Care for Persons of Childbearing Age With HIV) or as early as possible in pregnancy. In the United States, approximately 20% to 34% of infants with perinatal HIV exposure were born to people whose HIV diagnosis was not known before pregnancy.¹ Early diagnosis provides the best opportunity to improve the pregnant person’s health and pregnancy outcomes and to prevent infant acquisition of HIV. Universal voluntary HIV testing is recommended as the standard of care for all pregnant people in the United States by the Panel on Antiretroviral Therapy and Medical Management of Children Living With HIV and the Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission (the Panels), 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.^2-6 Providers should be aware that gaps in maternal HIV testing do occur and can contribute to missed opportunities for preventing perinatal HIV transmission.^7-10

All HIV testing should be performed in a manner that is consistent with state and local regulations. CDC recommends the “opt-out” approach, which is allowed in many jurisdictions and involves notifying a pregnant person that HIV testing will be performed as part of routine care unless they choose not to be tested.² The “opt-in” approach involves obtaining specific consent before testing, and this approach has been associated with lower testing rates.^11,12 Despite the guidelines for universal HIV screening of pregnant people, recent studies indicate that fewer than 80% of women report having been tested for HIV during pregnancy.^13,14 The mandatory newborn HIV testing approach, which has been adopted by several states, involves testing newborns with or without maternal consent. In some areas, this applies to all newborns; in others, it applies only to the infants of mothers who have declined prenatal or intrapartum testing.

There are multiple U.S. Food and Drug Administration (FDA)-approved tests available for the diagnosis of HIV infection. Clinicians should familiarize themselves with the testing available at their facilities, including the turnaround time for receiving results. For the purposes of this section, three types of testing are discussed: antigen/antibody immunoassays; antibody only immunoassays; and HIV nucleic acid tests (NAT).

• Antigen/antibody immunoassays: Most routine laboratory testing for HIV currently uses antigen/antibody tests. Because these tests also detect HIV p24 antigen, they can detect acute HIV infection as early as 1 to 2 weeks after appearance of HIV RNA and before appearance of HIV antibody. These tests also detect HIV-2 infection. Laboratory-based tests require trained laboratory staff, and results can be available within 1 hour, but in some hospitals the test may not be readily available 24 hours a day. One FDA-approved antigen/antibody test can be performed at the point of care (POC) and provides results within 30 minutes.
• Antibody-only immunoassays: Many antibody-only immunoassays in current use can be performed using blood from a finger stick or oral fluid and provide results within 30 minutes. Because of this very short turnaround time, they are often referred to as rapid tests. Many of these tests are also approved by the FDA for POC usage. Because these tests detect only antibody, acute HIV infection may be missed.
• HIV NAT: HIV-1 NAT tests detect HIV virus in blood. Depending on the type of HIV NAT, they may detect acute HIV infection, help diagnose HIV infection, and assess response to HIV therapy. Depending on the test, receiving results of an HIV-1 NAT may take several days. The HIV RNA assay is the preferred NAT for possible acute infection and perinatally acquired infection.

In this section, the term expedited is used to designate testing performed in situations when a very short turnaround time is optimal, such as when a mother is in labor but HIV status is undocumented. Expedited testing should be available in all delivery units 24 hours a day, and results should be available within 1 hour. Expedited testing is dependent on the available HIV tests in each facility and may include any of the three test types.

The Panels recommend that clinicians initiate HIV testing with an immunoassay that can detect HIV-‍1 antibodies, HIV-2 antibodies, and HIV-1 p24 antigen (referred to as an HIV antigen/antibody immunoassay). The Panels’ recommendations for HIV testing are based on CDC’s 2014 Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations.¹⁵

Individuals with a reactive antigen/antibody immunoassay should be tested further with an HIV-‍1/HIV-2 antibody differentiation assay (referred to as supplemental testing). Individuals with a reactive antigen/antibody immunoassay and a nonreactive differentiation test should be tested with an FDA-approved plasma HIV RNA assay to assess for acute HIV infection (see CDC’s 2018 Quick Reference Guide: Recommended Laboratory HIV Testing Algorithm for Serum or Plasma Specimens).

In some clinical settings, initial testing may be conducted with a rapid HIV test which detects only HIV antibodies. Clinicians should assess a pregnant person’s risk of acute HIV infection, particularly late in pregnancy, because people may receive a negative result for HIV immunoassays when they are in the window period (the time between infection and when the infection can be detected by a specific laboratory test). The antigen/antibody immunoassay may detect infection as early as 18 days after infection; antibody-only assays (such as rapid tests) may take as long 45 days. However, during this period, the person with acute HIV will be viremic,¹⁶ with a high risk of perinatal transmission to the newborn. The HIV RNA assay can detect the presence of HIV as early as 10 days post-infection. When acute HIV infection is suspected during pregnancy, during the intrapartum period, or while breastfeeding, a plasma HIV RNA assay should be performed in conjunction with an antigen/antibody immunoassay. See Early (Acute and Recent) HIV Infection for more information.

Timing and Benefits of HIV Testing in Pregnancy

Maternal HIV testing should be performed as early as possible during pregnancy, wherever a person seeks care (including emergency departments and prenatal clinics), to avoid missed opportunities to identify pregnant people with HIV. Repeat HIV testing should be performed in the third trimester for people who are at increased risk of acquiring HIV or who are living in areas of high HIV incidence. Repeat testing is also recommended when pregnant individuals are diagnosed with sexually transmitted infection (STI), or when they show symptoms and signs of acute HIV infection. Pregnant people with unknown or undocumented HIV status who present to care in labor should be tested before delivery or as soon as possible after delivery.^7-10 Because women are more susceptible to HIV acquisition during pregnancy and the postpartum period,¹⁷ HIV testing provides an opportunity for clinicians to initiate a discussion about preventive interventions, including educating and counseling about pre-exposure prophylaxis (PrEP) for a pregnant person without HIV who is at risk for acquiring HIV. See Pre-Exposure Prophylaxis (PrEP) to Prevent HIV During Periconception, Antepartum, and Postpartum Periods and guidance available on CDC’s Pre-Exposure Prophylaxis (PrEP) page for more information.

Determining an individual’s HIV status before they become pregnant or during the antenatal period enables—

• People with HIV to receive appropriate antiretroviral therapy (ART) and prophylaxis against opportunistic infections;
• Initiation of treatment in the identified people to maintain and improve their health and to decrease risk of HIV transmission to their fetus and their partners^2,18,19;
• Referral of partners for testing, which allows the partners to initiate either treatment if the results are positive or preventive interventions, including PrEP, if the results are negative (see Pre-Exposure Prophylaxis (PrEP) to Prevent HIV During Periconception, Antepartum, and Postpartum Periods);
• Counseling of pregnant people with HIV about recommended modes of delivery based on individualized risks of perinatal transmission of HIV^20-22;
• Provision of an appropriate antiretroviral (ARV) drug regimen to the newborn to reduce the risk of perinatal transmission;
• Counseling regarding infant feeding for individuals with HIV (see Infant Feeding for Individuals With HIV in the United States); and
• Early diagnostic evaluation of infants exposed to HIV (see Diagnosis of HIV Infection in Infants and Children), as well as testing of other children, to permit prompt initiation of ART and any indicated prophylaxis measures.^3,23-25

Discordant or False Positive HIV Tests

Discordant HIV testing results can be occur, requiring careful evaluation and often repeat tests. Early in HIV infection, before HIV seroconversion, the test combination of a positive antigen/antibody screen, negative HIV-1/HIV-2 antibody differentiation assay, and positive HIV RNA assay may be seen. This combination of results can occur because the immunoglobulin G–based antibody differentiation assay is positive later in infection than the antigen capture or the immunoglobulin M result in the antigen/antibody screen.

False-positive results do occur with HIV testing. The frequency of false-positive HIV testing is dependent on the prevalence of HIV in the population so may vary considerably. In a large urban hospital in Dallas, 21,163 women were screened using a combination antigen/antibody immunoassay and following the supplemental testing strategy recommended by the CDC algorithm. Of the 190 who tested positive, 28 were determined to have false-positive HIV yielding a positive predictive value of 83% (95% confidence interval [CI], 77-88%) and a false positive rate of 0.16% (95% CI, 0.11-0.22%), using the ARCHITECT HIV Ag/Ab assay.²⁶ For women screened a second time in pregnancy, the rate of false positive results relative to true positive results may be higher, as it depends on the community risk of HIV acquisition over a short time period (i.e., the 6 months between first- and third-trimester testing).

For any positive HIV screen late in pregnancy or during labor, an HIV RNA assay should be done at the same time as the supplemental HIV-1/HIV-2 antibody differentiation assay, as the HIV RNA assay will be needed to resolve questions raised by discordant results between the antigen/antibody screen and the antibody differentiation assay.

The combination of a positive HIV antigen/antibody screen with a negative supplemental HIV-‍1/HIV-2 antibody differentiation assay and a negative HIV RNA assay is seen in people without HIV who have a false-positive antigen/antibody screen.

Repeat HIV Testing in the Third Trimester

Repeat HIV testing during the third trimester, before 36 weeks gestation, is recommended for people with negative results on their initial HIV tests during pregnancy who—

• Are at high risk of acquiring HIV (e.g., those who inject drugs or have sex with people who inject drugs, those who exchange sex for money or drugs, those who are sex partners of individuals with HIV, those who have had a new sex partner or more than one sex partner during the current pregnancy,² or those who have a suspected or diagnosed STI during pregnancy)²⁷; or
• Are receiving health care in facilities where prenatal screening identifies one or more pregnant women with HIV per 1,000 women screened, or reside in a jurisdiction that has a high incidence of HIV in women between the ages of 15 and 45 years (see the 2006 Revised Recommendations for HIV Testing of Adults, Adolescents, and Pregnant Women in Health-Care Settings [PDF] [1]);^2,27 or
• Reside in states or territories with statutes or regulations that require third-trimester testing. In a 2020 article, these included Arkansas, Connecticut, Delaware, Florida, Georgia, Illinois, Louisiana, Maryland, Nevada, New Jersey, North Carolina, Tennessee, Texas, Virginia, and West Virginia.²⁸ Clinicians should check current requirements in their jurisdictions; or
• Have signs or symptoms of acute HIV (e.g., fever, lymphadenopathy, skin rash, myalgia, headaches, oral ulcers, leukopenia, thrombocytopenia, elevated transaminase levels).^2,27,29-31

In addition, third-trimester testing should be offered to pregnant people who perceive themselves as being at increased risk for HIV infection (regardless of whether or not they fit any of the above criteria). Pregnant people who decline testing earlier in pregnancy should be offered testing again during the third trimester.

An antigen/antibody immunoassay should be used for third-trimester testing because these tests have a higher sensitivity in the setting of acute HIV infection than older antibody tests.^15,32 If acute HIV infection is suspected, a plasma HIV RNA assay should be performed in conjunction with an antigen/antibody immunoassay. See Early (Acute and Recent) HIV Infection for more information.

Providers should be proactive in assessing a pregnant person’s HIV acquisition risk and implementing third-trimester HIV retesting when indicated. A study in Baltimore found that only 28% of women were retested for HIV despite the high incidence of HIV in Maryland and a high frequency of clinical risk factors.¹⁰ A study of data from 2007 to 2014 on children in Florida with perinatal HIV exposure found that perinatal HIV transmission was associated with poor or late prenatal care, diagnosis of HIV during labor and delivery or after birth, and, in some cases, acute maternal infection (as indicated by negative results for initial tests).³³ In a more recent study from a high-prevalence area in Florida, 91.7% of women had first- or second-trimester screening and, although only 82.2% had a third-trimester test, 89.3% of those without third-trimester screening had rapid testing upon admission.³⁴

HIV Testing During Labor in People With Unknown HIV Status

People in labor whose HIV status is undocumented and those who tested negative early in pregnancy but are at increased risk of HIV infection and were not retested in the third trimester should undergo expedited HIV testing to identify HIV infection in pregnant persons and HIV exposure in their infants.^{2-4,23,30,35,36}

• Perform an expedited HIV test—either an antigen/antibody immunoassay that can provide results within 1 hour or the most sensitive rapid test (includes rapid POC tests) available for persons in labor. An HIV RNA assay should also be performed for individuals with suspected acute HIV infection.
• If the initial HIV test result is negative (nonreactive), no further testing is required unless acute HIV infection is suspected (see Acute HIV Infection During Pregnancy or Breastfeeding below).¹⁵
• A positive antigen/antibody immunoassay or rapid HIV test result must be immediately followed by a supplemental HIV-1/HIV-2 antibody differentiation assay, as well as an HIV RNA assay for the mother and an HIV RNA assay for the infant.¹⁵ If possible, contact the laboratory to prioritize results.
• For delivery units, every effort should be made to have the ability to run a confirmatory supplemental test (HIV-1/HIV-2 antibody differentiation assay) seven days a week. If possible, results of HIV RNA assays should be available in 24 hours or less.
• For individuals with a positive HIV test result or suspected acute HIV infection during labor, provide counseling about HIV test results and implications for care.
  • Initiate IV zidovudine during labor; see Intrapartum Care for People With HIV
  • Immediately initiate an ARV regimen that is appropriate for infants who are at high risk of perinatal HIV transmission (see Antiretroviral Management of Newborns With Perinatal HIV Exposure or Perinatal HIV or contact the National Clinician Consultation Center Perinatal HIV/AIDS hotline).
  • For persons who were planning to breastfeed, breastmilk should be expressed and stored appropriately until all supplemental HIV test results are reviewed and negative.