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
Intrapartum Care
Intrapartum Antiretroviral Therapy/Prophylaxis
(Last updated:9/14/2011)
Panel’s Recommendations:
- Intrapartum intravenous zidovudine is recommended for all HIV-infected pregnant women, regardless of their antepartum regimen, to reduce perinatal transmission of HIV (AI).
- For women who are receiving a stavudine-containing antepartum regimen, stavudine should be discontinued during labor while intravenous zidovudine is being administered (AI).
- Women who are receiving an antepartum combination antiretroviral (ARV) drug regimen should continue this regimen on schedule as much as possible during labor and before scheduled cesarean delivery (AIII).
- Women receiving fixed-dose combination regimens that include zidovudine should receive intravenous zidovudine during labor while other oral ARV components are continued (AIII).
- For women who have received antepartum ARV drugs but have suboptimal viral suppression near delivery (i.e., HIV RNA >1,000 copies/mL), scheduled cesarean delivery is recommended (see Mode of Delivery) (AI). The addition of single-dose intrapartum/newborn nevirapine is not recommended (AI).
- Women of unknown HIV status who present in labor should undergo rapid HIV antibody testing (AII). If the results are positive, a confirmatory HIV test should be done as soon as possible and maternal/infant ARV drugs should be initiated pending results of the confirmatory test (AII). If the confirmatory HIV test is positive, infant ARV drugs should be continued for 6 weeks (see Neonatal Postnatal Care) (AI); if the test is negative, the infant ARV drugs should be stopped.
- Intravenous zidovudine is recommended for HIV-infected women in labor who have not received antepartum ARV drugs and infant combination ARV prophylaxis is recommended for 6 weeks (see Infant Antiretroviral Prophylaxis) (AII).
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Table 8 shows dosing for zidovudine, given intravenously as a continuous infusion during labor and during the neonatal period; Table 9 shows intrapartum and neonatal dosing for additional drugs to be considered in certain situations, as delineated below.
Women Who Have Received Antepartum Antiretroviral Drugs
Use of Intravenous Zidovudine during Labor
Results from PACTG 076 and subsequent epidemiologic studies have proven the efficacy of the three-part zidovudine chemoprophylaxis regimen, alone or in combination with other ARV agents. The PACTG 076 zidovudine regimen includes a continuous intravenous infusion of zidovudine during labor (initial loading dose of 2 mg/kg intravenously over 1 hour, followed by continuous infusion of 1 mg/kg/hour until delivery). Given results from this trial, intravenous zidovudine during the intrapartum period should be discussed with and recommended to all HIV-infected pregnant women. Administration of intravenous zidovudine should begin 3 hours before scheduled cesarean delivery, according to standard dosing recommendations. Women receiving fixed-dose combination regimens that include zidovudine, such as a zidovudine/lamivudine combination, should receive intravenous zidovudine during labor while other oral ARV components are continued. For example, in women who are receiving zidovudine/lamivudine during pregnancy, zidovudine should be given intravenously and lamivudine should be given orally during labor.
If antenatal use of zidovudine was precluded by known or suspected zidovudine resistance, intrapartum use of the drug still should be recommended, except in woman with documented histories of hypersensitivity. This intrapartum use of the drug is recommended because of the unique characteristics of zidovudine and its proven record in reducing perinatal transmission, even in the presence of maternal resistance to the drug (see Management of Antiretroviral Drug Resistance during Pregnancy). Because there is pharmacologic antagonism between zidovudine and stavudine, those drugs should not be coadministered during labor. Women who are receiving an antepartum stavudine-containing regimen should have the drug temporarily discontinued during labor while intravenous zidovudine is being administered, with other components of the regimen continued orally.
Continuation of Antenatal Antiretroviral Drugs during Labor
Women who are receiving an antepartum combination ARV drug regimen should continue that regimen on schedule as much as possible during the intrapartum period to provide maximal virologic effect and to minimize the chance of development of drug resistance. When cesarean delivery is planned, oral medications can be continued preoperatively with sips of water. Medications requiring food ingestion for absorption can be taken with liquid dietary supplements, contingent on consultation with the attending anesthesiologist in the preoperative period. If the maternal ARV regimen must be interrupted temporarily (e.g., for less than 24 hours) during the peripartum period, all drugs should be stopped and reinstituted simultaneously to minimize the chance that resistance will develop.
Women Who Have Received Antepartum Antiretroviral Drugs But Have Suboptimal Viral Suppression Near Delivery
Women who have received combination ARV drug regimens may not achieve complete viral suppression by the time of delivery because of factors such as poor adherence, viral resistance, or late entry into care. Regardless of the reason, all women who have HIV RNA levels >1,000 copies/mL near the time of delivery should be offered a scheduled cesarean delivery at 38 weeks, which may significantly reduce the risk of transmission (see Transmission and Mode of Delivery).
The addition of single-dose nevirapine during labor has not been shown to reduce perinatal transmission of HIV in this group of women. The PACTG 316 study, conducted in women in the United States, Europe, Brazil, and the Bahamas who were receiving ARV drugs during pregnancy (primarily combination therapy), showed that the addition of single-dose nevirapine did not reduce the risk of mother-to-child transmission of HIV, even in the setting of maternal viremia. It was, however, associated with the development of nevirapine resistance in 15% of women with detectable HIV RNA levels postpartum [1-2]. Given the risk of development of resistance and the lack of data to suggest added efficacy, addition of single-dose nevirapine is not recommended in women who have received combination antepartum ARV drugs.
Use of additional medications for prophylaxis in infants may be warranted in special circumstances, such as in cases where maternal HIV RNA levels are high at or near the time of delivery, especially if delivery is not a scheduled cesarean delivery (see Infant Antiretroviral Prophylaxis and Table 9). However, no additional intrapartum interventions are indicated for the mothers.
Women Who Have Not Received Antepartum Antiretroviral Drugs
Women Who Present in Labor Without Documentation of HIV Status
All women with undocumented HIV status or without documentation of HIV status at the time of labor should be screened with rapid HIV testing unless they decline (opt-out screening). Rapid HIV testing is also recommended for women presenting in labor who tested negative for HIV in early pregnancy but are at increased risk of HIV infection and were not retested in the third trimester [3]. Factors that may increase risk of infection include diagnosis of a sexually transmitted infection (STI), illicit drug use or exchange of sex for money or drugs, multiple sexual partners during pregnancy, a sexual partner at risk of HIV infection, signs/symptoms of acute HIV infection, or living in a region with an elevated incidence of HIV in women of childbearing age and not undergoing repeat HIV testing in the third trimester [3].
Rapid HIV antibody testing should be available on a 24-hour basis at all facilities with a maternity service and/or neonatal intensive care unit. Statutes and regulations regarding rapid testing vary from state to state; see http://www.nccc.ucsf.edu/consultation_library/state_hiv_testing_laws for a review of state HIV testing laws. Current information on rapid testing also should be available at all facilities with a maternity service and/or neonatal intensive care unit.
Women with positive rapid HIV antibody tests should be presumed to be infected until standard HIV antibody confirmatory testing clarifies their infection status. Along with confirmatory HIV antibody testing, these women should receive appropriate assessments as soon as possible to determine their health status and make recommendations for whether antiretroviral therapy (ART) is needed based on that status. Arrangements also should be made for establishing HIV care and providing ongoing psychosocial support after discharge. Intravenous zidovudine should be started immediately in all women with positive rapid HIV tests in labor to prevent perinatal transmission of HIV, as discussed below.
Choice of Intrapartum/Postpartum Antiretroviral Regimen for Women without Antepartum Antiretroviral Therapy
All HIV-infected women who have not received antepartum ARV drugs should have intravenous zidovudine started immediately to prevent perinatal transmission of HIV (see Table 8 for dosing information). Although intrapartum/neonatal ARV medications will not prevent perinatal transmission that occurs before labor, most transmission occurs near to or during labor and delivery. Pre-exposure prophylaxis for the fetus can be provided by giving mothers a drug that rapidly crosses the placenta, producing fetal systemic ARV drug levels during intensive exposure to HIV in maternal genital secretions and in blood during birth. In general, zidovudine and other nucleoside reverse transcriptase inhibitor (NRTI) drugs and non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs cross the placenta well, whereas protease inhibitors (PIs) do not (see Table 5).
Epidemiologic data indicate that intravenous maternal intrapartum zidovudine followed by oral zidovudine for 6 weeks for the infant significantly reduces transmission compared with no treatment [4]. In a New York State cohort study, transmission rates were 10% with intrapartum and neonatal zidovudine compared with 27% without zidovudine, a 62% reduction in risk [4]. The PETRA study demonstrated that intrapartum prophylaxis alone, without an infant post-exposure prophylaxis component, is not effective in reducing perinatal transmission [5].
A large international trial (NICHD-HPTN 040/PACTG 1043) demonstrated that adding ARV agents to the neonatal portion of the intrapartum/neonatal zidovudine regimen can further reduce mother-to-child transmission of HIV for mothers who have received no antepartum ARV drugs (see Infant Antiretroviral Prophylaxis). In this study, women who had not received antepartum ARV drugs received only intravenous zidovudine, whereas their infants received zidovudine in combination with other agents, achieving a 50% reduction in transmission. Therefore, no additional intrapartum drugs, including intrapartum maternal single-dose nevirapine, are indicated for the woman in this situation [6].
References:
1. Dorenbaum A, Cunningham CK, Gelber RD, et al. Two-dose intrapartum/newborn nevirapine and standard antiretroviral therapy to reduce perinatal HIV transmission: a randomized trial. JAMA. 2002 Jul 10;288(2):189-198.
2. Cunningham CK, Chaix ML, Rekacewicz C, et al. Development of resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent perinatal human immunodeficiency virus type 1 transmission: a substudy of pediatric AIDS clinical trials group protocol 316. J Infect Dis. 2002 Jul 15;186(2):181-188.
3. Centers for Disease Control and Prevention (CDC). Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006 Sep 22;55(RR-14):1-17; quiz CE11-14.
4. Wade NA, Birkhead GS, Warren BL, et al. Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human immunodeficiency virus. N Engl J Med. 1998 Nov 12;339(20):1409-1414.
5. Petra Study Team. Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (Petra study): a randomised, double-blind, placebo-controlled trial. Lancet. 2002 Apr 6;359(9313):1178-1186.
6. Nielsen-Saines K, Watts DH, Santos VV, et al. Phase III randomized trial of the safety and efficacy of three neonatal antiretroviral regimens for preventing intrapartum HIV-1 transmission (NICHD HPTN 040/PACTG 1043). Paper presented at: 18th Conference on Retroviruses and Opportunistic Infections (CROI); Feb. 27-Mar.3, 2011; Boston, MA.