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Discussion

Rationale for HIV Testing during Labor and Delivery

The World Health Organization estimates that in 2010, only 61% of pregnant women in Eastern and Southern Africa were tested for HIV during pregnancy[1]. Performing HIV testing in pregnancy is critically important because establishing the diagnosis of maternal HIV infection allows for implementation of additional measures that can significantly improve the mother's health and reduce the risk of HIV transmission to her infant[1,2]. Although initial HIV testing should ideally be performed early in pregnancy, diagnosing HIV infection later in pregnancy—even during labor and delivery with rapid HIV testing—still allows for interventions that are highly beneficial to the mother and her infant. Furthermore, pregnancy is a high-risk period for HIV acquisition[3,4,5]: a study from Kenya noted that 2.6% of women who were HIV negative antenatally tested positive at 6 weeks postpartum[6], and a similar study in South Africa found that 3.4% of HIV-negative women seroconverted during pregnancy[3]. The WHO therefore recommends that women in high-prevalence regions who undergo HIV testing early in pregnancy should be systematically offered repeat HIV testing in the third trimester of pregnancy, or should be tested in labor if testing is not performed in the third trimester[2].

Feasibility and Acceptability of Testing during Labor and Delivery

Studies performed in multiple countries have found that rapid HIV testing in labor is both feasible and acceptable to women. For example, 98% of women in India accepted testing in the labor ward[7], 66% of women in South Africa consented to testing in the labor and delivery room[8] (among those who declined HIV testing, 37% did so because they already knew their HIV status), and 88% of women in Cameroon accepted HIV testing[9]. Rapid testing protocols have worked well in research settings, with studies reporting that they are able to deliver results to women within 60 minutes[8].

Protocols for HIV Testing in Labor

While rapid testing protocols generally require 2 positive rapid antibody tests from different manufacturers to confirm HIV infection, protocols in labor wards typically recommend offering PMTCT services to mothers as soon as one rapid test is positive in order to avoid delays in administering prophylactic antiretroviral therapy. Similarly, women with discordant rapid tests are usually offered PMTCT interventions while confirmatory testing is pursued[10].

PMTCT Interventions for Women Diagnosed with HIV during Labor

Appropriate interventions for women diagnosed with HIV during labor and delivery will depend on which PMTCT option has been adopted in that region. The WHO encourages countries with limited resources to adopt one of three PMTCT strategies (Options A, B, or B+) for HIV-infected pregnant women (Figure 1)[11].

  • Option A Countries: In settings where WHO Option A (maternal antepartum zidovudine plus single-dose nevirapine at delivery) is the standard PMTCT protocol, all HIV-infected women in labor who are not already on antiretroviral therapy should receive a single dose of 200 mg oral nevirapine immediately. Oral zidovudine (300 mg twice daily) and lamivudine (150 mg twice daily) should also be started as soon as possible and continued throughout labor and for 7 days after delivery; this one-week 'tail' of zidovudine-lamivudine reduces the risk of evolution of nevirapine-induced NNRTI resistance in mothers who receive single-dose nevirapine during labor[12]. The first dose of nevirapine and zidovudine-lamivudine can be administered as a single fixed-dose combination tablet of zidovudine/lamivudine/nevirapine, or the component medications can be given separately. The primary role of the maternal dose of single-dose nevirapine is to reduce the risk of HIV transmission to the infant during delivery and early breastfeeding; the efficacy of this approach was established by the HIVNET 012 trial (Figure 2)[12].
  • Option B and B+ Countries: Women in countries that have adopted the WHO "Option B" or "Option B+" approaches (maternal antepartum triple antiretroviral therapy) should start triple antiretroviral therapy immediately upon diagnosis of HIV infection and continue until one week after all infant exposure to breastmilk has stopped; if there is any delay in initiating a triple regimen, then the Option A regimens would apply. After delivery, triple antiretroviral therapy will continue for life among women in countries that have adopted the "Option B+" approach; for women in countries that have adopted the "Option B" approach, continuation of lifelong triple antiretroviral therapy will depend upon whether or not the mother needs therapy for her own health.

PMTCT Interventions for the Infant when Mother Diagnosed with HIV during Labor

Infant PMTCT interventions depend primarily upon whether or not the infant will receive breastmilk.

  • Breastfeeding Infants:
    • Option A: Infants who will receive breastmilk should be given daily nevirapine from birth until 1 week after all exposure to breastmilk has ended, or for a minimum of 6 weeks if breastfeeding ceases before 6 weeks.
    • Option B or B+: Infants should receive six weeks of daily nevirapine prophylaxis when the mother is on triple antiretroviral therapy. If the mother starts triple antiretroviral therapy late in pregnancy, during labor or shortly after delivery, infant nevirapine prophylaxis should be extended longer than six weeks, but can be discontinued when the mother's antiretroviral therapy regimen is expected to fully suppress her HIV RNA levels (the BAN study indicates that 12 weeks of nevirapine provided superior protection for infants compared to 6 weeks when women initiated antiretrovirals at delivery)[14].
    • Nevirapine Dosing: The dosing of extended nevirapine prophylaxis is based on the infant's age (Figure 3)[2].
  • Formula Feeding Infants: The WHO does not endorse formula feeding of infants born to HIV-infected mothers in resource-limited settings, as this practice has been associated with increased rates of infant mortality. The risk of breastmilk HIV transmission to the infant can be significantly reduced with maternal and/or infant antiretroviral prophylaxis[15,16,17]. In the situation where an infant is born to an HIV-infected mother and will not be exposed to breastmilk, the infant should still receive prophylaxis. Infants who are not breastfeeding should complete 4 to 6 weeks of therapy consisting of either daily nevirapine starting immediately or single-dose nevirapine at birth followed by twice-daily zidovudine prophylaxis[6].

Post-delivery Evaluation and Care of Mothers

Women tested in labor often do not receive the full benefit of usual post-test counseling for HIV. At some point after delivery, mothers who test positive for HIV in labor should receive standard post-test counseling and education, including encouraging women to bring partners in for testing, support for disclosure, and HIV prevention education (Figure 4)[2].

  • Option A: Women in Option A countries should be evaluated as soon as possible for eligibility for triple antiretroviral therapy, by obtaining a detailed past medical history and laboratory studies including a serum CD4 count. If triple antiretroviral therapy is indicated for her own health, it should be initiated as soon as possible.
  • Option B or B+: Women in Option B or B+ countries should initiate ART immediately and enroll in HIV care.

Cesarean Section for PMTCT in Resource-Limited Settings

Elective Cesarean section performed prior to the onset of labor and while the membranes are intact reduces intrapartum HIV transmission to infants of women who did not receive antenatal combination antiretroviral therapy[18,19].  Cesarean section has not been shown to provide additional benefit to women with a plasma HIV viral load less than 1000 copies/ml at delivery. Furthermore, even in resource-rich settings, Cesarean sections for HIV-infected women are associated with relatively high rates of surgical complications[20]. In resource-limited settings, post-operative wound infection rates have been recorded as high as 19 to 25% for HIV positive and HIV negative women[2,11]. For these reasons, Cesarean section is not recommended in resource-limited settings as an intervention to reduce mother-to-child transmission of HIV.

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  • The following link will open in a new window.
    Figure 1. WHO-Recommended PMTCT Strategies  (<em>Options</em>) for Pregnant Women in Resource-Limited Countries

    The WHO recommends that resource-limited countries implement nationally one of three PMTCT "Options". Option A recommends zidovudine monotherapy during antenatal care for those women who do not qualify for triple antiretroviral therapy. Options B and B+ provide triple antiretroviral therapy to all pregnant women regardless of their stage of HIV disease. Triple antiretroviral therapy is continued for life to all women under Option B+; under Option B women with a CD4 count greater than 350 cells/mm3 stop antiretrovirals when they stop breastfeeding.
    Source: World Health Organization (WHO). Programmatic update. Use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants. April 2012.


    Figure 1
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    Figure 2. Efficacy of Single-Dose Nevirapine for Prevention of Mother to Child Transmission of HIV in the HIVNET 012 Trial

    In the HIVNET 012 trial, single dose nevirapine given to mothers in labor and to the newborn reduced HIV transmission to infants by 47% when compared to mothers and infants who received zidovudine in labor and for 7 days postpartum. This benefit is from the long half-life of nevirapine which protects infants during early breastfeeding; the benefit continued for 18 months of follow up.
    Source: Jackson JB, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial. Lancet. 2003;362:859-68. Figure reproduced with permission. © Copyright 2003 Elsevier Ltd. All rights reserved.


    Figure 2
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    Figure 3. Extended Simplified Infant Nevirapine Dosing

    This table outlines appropriate dosing of nevirapine for infants on extended prophylaxis while breastfeeding.
    Source: World Health Organization. Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants: recommendations for a public health approach. – 2010 version. WHO, Geneva, 2010.


    Figure 3
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    Figure 4. WHO-Recommended Package of Essential Services for Quality Maternal Care, and Additional Services Recommended for HIV-Infected Women

    Source: World Health Organization. Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants: recommendations for a public health approach. – 2010 version. WHO, Geneva, 2010.


    Figure 4