Approach

It is recommended that all pregnant women be tested for HIV as early as possible in pregnancy. Early diagnosis of maternal HIV infection and initiation of antiretroviral therapy (ART) can optimize maternal health and greatly reduce the risk of perinatal transmission. The recommended HIV screening test is the fourth-generation enzyme-linked immunosorbent assay (ELISA), which detects HIV-1 and HIV-2 antibodies and HIV-1 p24 antigen. If the screening ELISA is positive, confirmatory testing with HIV-1/HIV-2 differentiation immunoassay (or, if unavailable, western blot or indirect immunofluorescence assay) is needed for diagnosis.

Clinical evaluation

Universal HIV prenatal screening is recommended, as history and risk-factor-based screening can lead to missed diagnoses. Nonetheless, the following key risk factors, if present, increase the possibility of maternal exposure to HIV infection, and should be elicited during the first prenatal assessment:

  • History of past or current injection drug use

  • History of past or current sexually transmitted infections

  • History of unprotected sexual encounters during pregnancy (including receptive anal intercourse and penile-vaginal intercourse)

  • History of multiple sexual partners or transactional sex.

A thorough history and physical exam should be performed for all pregnant women with HIV. The medical history should include inquiry into opportunistic infections or AIDS-defining illnesses, tuberculosis, sexually transmitted infections, medication use, vaccine and immunization status, mental illness, and substance abuse. Women should be screened for fever and weight loss as possible indicators of an underlying opportunistic infection such as tuberculosis.

Patients who present 2-4 weeks post exposure may have symptoms and signs of acute retroviral syndrome, characterized by fever, malaise, lymphadenopathy, and rash (typically a maculopapular blanching rash). These women should be retested for HIV regardless of previous results. Signs suggestive of advanced HIV infection include oral candidiasis, increasing dyspnea, and weight loss.

Maternal HIV testing

HIV testing is recommended in all sexually active women and should be a routine component of preconception care. The potential HIV exposure should be assessed in all women who are considering becoming pregnant. All pregnant women should be tested for HIV as early as possible in each pregnancy. Partners of pregnant women should also be encouraged to undergo testing if their HIV status is unknown.[7]

The fourth-generation ELISA, which detects HIV-1 and HIV-2 antibodies and HIV-1 p24 antigen, is recommended for screening as it can detect HIV infection earlier than third-generation assays. If the screening ELISA is positive, confirmatory testing with HIV-1/HIV-2 differentiation immunoassay (or, if unavailable, western blot or indirect immunofluorescence assay) is needed for diagnosis. If the HIV-1/HIV-2 antigen/antibody combination immunoassay result is reactive and HIV-1/HIV-2 antibody differentiation immunoassay is nonreactive or indeterminate, the specimen should be tested with an HIV-1 nucleic acid test.[7][71]​​​ If there is clinical concern for acute HIV infection during pregnancy, the intrapartum period, or while breast-feeding, HIV-1 RNA testing is recommended (in conjunction with HIV antigen/antibody testing).[7][72]

Opt-out screening (i.e., routine testing for HIV except where a patient declines) is recommended as a part of prenatal laboratory testing. However, you should consult your local regulations. Women who decline HIV testing because of a previous negative HIV test should be informed of the importance of retesting during pregnancy.

The need for repeat testing depends on the testing modality used and its window period.​ Repeat testing in the third trimester (before 36 weeks’ gestation) is recommended for pregnant women with initial negative tests during pregnancy who:[7][73]​​

  • Are at high risk of acquiring HIV

  • Are receiving health care in facilities that have an HIV incidence of at least 1 case per 1000 pregnant women per year or reside in jurisdictions with elevated HIV incidence in females ages 15-45 years

  • Reside in states that require third trimester-testing

  • Have signs or symptoms of acute infection

​Repeat testing should also be considered at other points in the pregnancy as clinically indicated (e.g., symptoms suggestive of a sexually transmitted infection, ongoing exposure to HIV). Testing should also be offered to pregnant women who perceive themselves to be at increased risk for HIV infection (regardless of whether or not they fit any of the above criteria).[7]

Expedited HIV testing (i.e., testing performed in situations where a very short turnaround time is optimal) should be performed during labor (or after delivery) in women with undocumented HIV status, and those who tested negative early in pregnancy but had increased exposure to HIV and were not retested in the third trimester. HIV antigen/antibody testing should be available 24 hours a day and results should be available within 1 hour. If fourth-generation ELISA is not available, initial testing should be performed by the most sensitive expedited or rapid test available. If results are positive, maternal intrapartum ART prophylaxis (with zidovudine) should be started immediately. Women who have not been tested before or during labor should undergo expedited testing in the immediate postpartum period.[7]

When a pregnant woman has a positive HIV test during labor, delivery, or postpartum, supplemental HIV testing should be performed on the mother (i.e., HIV-1/HIV-2 antibody differentiation assay, HIV RNA assay), as well as on the infant (i.e., HIV RNA assay).[7]

Discordant test results and false-positive results can occur, and careful evaluation and repeat tests may be required.[7]

Rapid tests may be used for initial testing in some clinical settings. These tests may detect a combination of antigen and antibodies, or antibodies only. A positive result on a rapid test should be followed by laboratory-based testing for confirmation.[7]

Postpartum women who are at increased risk of HIV acquisition or who request testing should be offered HIV testing (as well as pre-exposure prophylaxis).[7]

Additional maternal testing and monitoring

In addition to routine prenatal laboratory screening and care, pregnant women with HIV need additional laboratory testing to assess their HIV health status.

  • CD4 count: indicated to monitor the health of the immune system. Testing should be performed at the initial visit (with a review of prior CD4 counts). Repeat every 3 months during pregnancy in patients who have been on treatment for <2 years, patients with CD4 counts <300 cells/microliter, and patients with inconsistent adherence and/or detectable viral loads. Women who have been on ART for ≥2 years with consistent viral suppression and CD4 counts consistently ≥300 cells/microliter do not require further monitoring during pregnancy. Women who have been on ART for <2 years with CD4 counts ≥300 cells/microliter should be monitored every 6 months.[7]​ Do not test for other more complex lymphocyte panels (such as CD8 count or CD4/CD8 ratio), as they add cost without offering clinical benefit.[74]

  • HIV RNA levels (viral load): indicated to monitor viral suppression. Testing should be performed at the initial visit (with a review of prior HIV RNA levels), 2-4 weeks after initiating or changing drug treatment, monthly until HIV RNA levels are undetectable, and then at least every 3 months during pregnancy. HIV RNA levels should also be assessed at approximately 36 weeks’ gestation (or within 4 weeks of delivery) to inform decisions about mode of delivery.[7]

​All pregnant patients with HIV will also have: baseline laboratory testing of renal and hepatic function; a complete blood count; and drug resistance testing (genotyping) to aid in determining an appropriate ART regimen. Initiation of ART should not be delayed due to genotype testing. Laboratory testing to monitor complications of specific ART regimens should be based on what is known about the adverse effects of the drugs an individual is receiving. Standard gestational diabetes screening is recommended for women on ART. Some experts may perform glucose screening earlier in pregnancy for patients who are on protease inhibitors, and who may be at high risk for gestational diabetes.[7]

Women should have an ultrasound as soon as possible to confirm gestational age. As amniocentesis should be performed only if clinically indicated after initiation of ART and, ideally, once HIV RNA levels are undetectable, noninvasive genetic screening is encouraged. Consider a consultation with an expert if a pregnant woman with detectable HIV RNA levels requires amniocentesis.[7]

Screening for tuberculosis, viral hepatitis, and sexually transmitted infections should be done early in every pregnancy. Consult local guidance for information on other prenatal standard of care assessments that may be required.

Diagnosis in exposed infants

The HIV-exposed infant should be tested for HIV infection and referred to specialty care if the test is positive. Virologic assays, either HIV DNA or RNA polymerase chain reaction (PCR) tests, should be used to detect HIV in infants <18 months of age with perinatal and postpartum HIV exposure. Testing is recommended in all infants with perinatal HIV exposure at 14-21 days; 1-2 months; and 4-6 months. Testing at birth should be considered in infants at high risk of infection (and 2-6 weeks after cessation of ART prophylaxis). A positive result should be confirmed by repeat testing on a second specimen as soon as possible. An assay that detects HIV non-B subtype viruses or group O infections is recommended in infants and children born to mothers with known or suspected non-B subtype virus or group O infections.[7]

For infants with perinatal exposure who are being breast-fed, testing should be considered at birth, 14-21 days, 1-2 months, and 4-6 months of age, with an additional test performed between the 1-to-2-month and 4-to-6-month tests, if the gap between tests is more than 3 months. Testing should be performed every 3 months during breast-feeding, and 4-6 weeks, 3 months, and 6 months after breast-feeding has ceased.[7]

HIV can be excluded in infants who have not been breast-fed with 2 or more negative tests (either 1 test obtained at ≥1 month of age and 1 at ≥4 months of age, or 2 tests from separate specimens at ≥6 months of age). Additional testing is generally not needed after this, but infants with potential exposure after birth require additional testing (i.e., virologic testing for those <18 months, and HIV antigen/antibody testing for those ≥18 months). Age-appropropriate testing is also recommended for infants and children with signs and symptoms of HIV, even in the absence of exposure.[7]

Zidovudine monotherapy for perinatal prophylaxis has not been shown to delay detection of HIV or decrease the sensitivity or predictive value of virologic assays.[75][76] However, the performance of these tests when the mother has received more intensive ART has not been studied. ART in an HIV-exposed infant may lead to delayed diagnosis by HIV DNA PCR.

In the case that a mother without a known diagnosis of HIV tests positive for HIV during labor, delivery, or postpartum, HIV RNA testing is recommended for the infant as early as possible, along with perinatal prophylaxis as above. If maternal HIV test results are not available at birth, the infant should be tested using an expedited antibody test to identify perinatal exposure. If the result of the infant’s test is positive, an HIV RNA assay should be performed on the infant and the infant should be immediately referred to a pediatric infectious disease specialist for management; the mother should be offered standard HIV diagnostic testing as soon as possible.[7]

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