Author: Carolyn K. Burr, EdD, RN
This chapter describes strategies for reducing the risk of perinatal HIV, based on the U.S. Department of Health and Human Services (DHHS) 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. It is not intended to be a comprehensive discussion of these topics, and all HIV-infected pregnant women should be treated by an HIV-experienced obstetrician and an HIV specialist. For centers that do not have HIV specialists available, experts at the National Perinatal HIV Consultation and Referral Service are available for consultation through the Perinatal HIV Hotline (888-448-8765). For more information on other aspects of caring for HIV-infected pregnant women, see chapter Care of HIV-Infected Pregnant Women.
Unless otherwise referenced, the information in this chapter is based on the most recent DHHS perinatal guidelines available at the time this chapter was published. Consult the AIDSinfo website for the most current recommendations.
In the absence of antiretroviral (ARV) prophylaxis or other interventions, the rate of perinatal HIV transmission in the United States ranges from 16% to 25%. Antiretroviral therapy (ART) is highly effective in reducing the risk of perinatal transmission of HIV, to as low as 1-2%. All pregnant women with HIV infection should be educated about the risks of perinatal HIV transmission and offered ART and other medical management to maintain or improve their own health and to reduce the risk of HIV transmission to their infants.
In 1994, the Pediatric AIDS Clinical Trial Group study 076 (PACTG 076) found that ARV treatment during pregnancy could significantly reduce the risk of HIV transmission to infants. The intervention, consisting of zidovudine (ZDV) given PO to the women during the last weeks of pregnancy and IV during labor and delivery, as well as to the newborns for 6 weeks, reduced the rate of infant infection from 25.5% to 8.3%. The ZDV regimen quickly became the standard of care in the United States and other high-income countries. Subsequent studies showed that combination ARV regimens with suppression of maternal HIV viral load to undetectable levels further reduced the risk of perinatal infection.
Studies in resource-limited countries as well as in resource-abundant areas have examined various ARV strategies for reducing the risk of perinatal HIV transmission. The Petra study, a placebo-controlled trial in a breast-feeding population in Uganda, South Africa, and Tanzania, found a transmission rate of 8.9% among women who received PO ZDV plus lamivudine (3TC) intrapartum and for 1 week postpartum and whose infants also received 1 week of ZDV/3TC, compared with a rate of 15.3% in the placebo group. The HIV NET 012 trial in a breast-feeding population in Uganda compared the efficacy of a single dose of nevirapine given to the mother at the onset of labor plus a single dose given to the newborn 48 hours postpartum with that of PO ZDV given to the mother during labor and to the newborn. The transmission rate was 11.8% in the nevirapine arm compared with 20.0% in the ZDV arm. The results of this study and the low cost of nevirapine prompted a number of resource-limited countries to institute nevirapine prophylaxis as the standard of care for preventing mother-to-child transmission of HIV. Numerous other trials have demonstrated the efficacy of various ARV strategies, combining different ARVs with different treatment durations and given to mothers, newborns, or both, in both breast-feeding and non-breast-feeding populations. Research has shown that ARV interventions even late in the peripartum or newborn periods may decrease the infant's risk of HIV infection. A retrospective study of subjects in New York found that the rate of perinatal HIV transmission was 9.3-10% if ZDV was given either to both the mothers intrapartum and their newborns or to the newborns only, compared with 26.6% if no ARV medication was given. This study underscores the importance of offering ARV interventions to pregnant women with HIV infection whenever they are identified in pregnancy or during labor and delivery, or as an intervention with the newborn.
In the United States, the PACTG 076 regimen remains an important component in the prevention of perinatal HIV transmission, and usually is incorporated into combination ART for pregnant women. For international settings, other guidelines have been developed by global agencies such as the World Health Organization (see References, below) and by individual governments.
Mother-to-child transmission also can occur through breast-feeding. Recent studies have shown that ART given to the nursing mother and/or to her infant decreases the risk of transmission to the infant. However, because substitute feeding in the United States is safe, affordable, feasible, sustainable, and available, mothers in the United States should not breast-feed.
The success of interventions to reduce the risk of perinatal HIV transmission has been achieved through the routine HIV testing and counseling of all pregnant women. Interventions to prevent transmission can be effective only if women know their HIV status and have access to treatment. The DHHS has recommended universal HIV counseling and testing for pregnant women since 1995. Many national professional and governmental organizations, including the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the U.S. Preventive Services Task Force, endorse those recommendations. Current recommendations from the U.S. Centers for Disease Control and Prevention (CDC) feature the following three approaches to HIV testing during pregnancy:
State laws regarding HIV testing during pregnancy vary widely, and many are currently under review. A number of states have adopted the opt-out approach, whereas some still require written informed consent before an HIV test is done. Others require patient education and a chart note from the providers. Clinicians should be familiar with relevant state laws regarding HIV testing during pregnancy, opt-out or consent provisions, and regulations about rapid HIV testing during the intrapartum or newborn period. (Information on state laws regarding HIV testing during pregnancy can be found at the National HIV/AIDS Clinicians' Consultation Center's Compendium of State HIV Testing Laws. Whatever the consent process, a woman should know that an HIV test is being done and should receive at least the information outlined below.
Educating pregnant women about the importance of HIV testing is a critical element in preventing perinatal HIV transmission. However, extensive pretest counseling is not essential. A woman must be told that HIV testing is a standard component of prenatal care, that her clinician recommends the tests, and that all pregnant women should be tested for HIV because knowing about HIV infection is important for their health and the health of their babies. Research has shown that a provider's strong endorsement of HIV testing is a major predictor of whether a woman receives an HIV test. Testing should be voluntary and free of coercion, and a woman should know that she can decline testing without the risk of being denied care. A woman's age, cultural background, educational level, and primary language may influence her knowledge about HIV transmission and her willingness to be tested; the clinician should consider these factors carefully when providing education and information.
The following minimum information should be provided through an educational session with a health care provider or through written or electronic media (e.g., brochures, videos):
Women should be told that test results are confidential to the extent allowed by law and that medical and other services are available for women with HIV infection. Reporting requirements for the specific state should be explained.
HIV testing should be performed as early in pregnancy as possible to allow for interventions to prevent transmission and for effective management of a woman's HIV infection, if the woman is found to be HIV seropositive. The CDC recommends repeat HIV testing in the third trimester for women who receive health care in jurisdictions with an elevated incidence of HIV or AIDS among women, as well as for women at high risk of acquiring HIV (e.g., a history of injection drug use, exchange of sex for money or drugs, multiple sex partners, or a partner known to be HIV infected). Jurisdictions in which repeat third trimester testing is recommended include Alabama, Connecticut, Delaware, District of Columbia, Florida, Georgia, Illinois, Louisiana, Maryland, Massachusetts, Mississippi, Nevada, New Jersey, New York, North Carolina, Pennsylvania, Puerto Rico, Rhode Island, South Carolina, Tennessee, Texas, and Virginia. Any pregnant woman with signs or symptoms of acute HIV infection should be evaluated (see chapter Primary HIV Infection) and receive an HIV plasma RNA test as well as an antibody test. A number of states mandate a third-trimester HIV test for all pregnant women. If the client declines testing at any point, the clinician should inquire about her reasons and follow up at subsequent visits. If the provider is persistent, the woman may choose to have an HIV test at a later visit.
In the United States, the vast majority of pregnant women who are tested for HIV will be HIV seronegative. When giving test results to an HIV-negative woman, the clinician should take the opportunity to discuss risk-reduction strategies to help ensure that she remains uninfected by HIV. Women at high risk of HIV infection should be referred for more extensive counseling because some research indicates that pregnancy may place them at greater risk of acquiring HIV infection, and acute HIV infection may confer greater risk of transmission to the fetus.
Counseling a pregnant woman with a positive HIV test result requires knowledge and sensitivity. The clinician should explain that, even though the woman may feel well, she is infected with the virus. The woman should be told about the importance of medical management of HIV for her own health and for the prevention of perinatal transmission, and she should be guided to the medical and social services available in her local community. She also should be referred to an HIV obstetric specialist who can work closely with her primary obstetric and HIV providers to manage her care during the pregnancy. The patient may be surprised or shocked upon receiving the HIV diagnosis, or she may have known her status but been reluctant to disclose it. The clinician should emphasize the importance of emotional and social support, assess the patient's social support resources, and offer her referrals as needed.
As discussed earlier, beginning ART during pregnancy offers the greatest chance for preventing perinatal transmission of HIV, but interventions during the intrapartum and neonatal periods also offer opportunities to decrease the risk of HIV transmission. Rapid HIV testing for women who present in labor with unknown or undocumented HIV status can identify women who are infected with HIV so that interventions can be offered. Available rapid HIV antibody tests are both sensitive and specific and provide results in as little as 20 minutes.
Women who should receive HIV testing during labor include the following:
Education and counseling for the woman in labor who needs an HIV test should incorporate the information for prenatal education discussed earlier, with consideration given to the special circumstances of labor. Special educational formats such as flip charts have been developed to help with patient education. Confidentiality should be assured for the information and consent process and for treatment. If an opt-out approach is used in the labor setting, a woman of unknown serostatus should be told that no HIV test is found on her chart, that HIV testing is part of routine care, and that she can decline if she wishes, but that experts recommend HIV testing because available interventions can decrease her baby's risk of becoming infected with HIV if she is found to be seropositive.
Perinatal transmission is most likely to occur in the intrapartum period. Several factors influence the risk of transmission from mother to infant. One of these is the mother's HIV RNA level (viral load). Clinical trials and observational studies have shown a strong positive correlation between maternal HIV viral load during pregnancy or at delivery and the risk of perinatal HIV transmission, even among women receiving treatment with ARVs. However, HIV transmission may occur at any level of maternal HIV RNA, including (rarely) when the viral load is undetectable. ARV prophylaxis is a critical factor in reducing HIV transmission. For women on effective combination ART with undetectable HIV RNA, the rate of perinatal HIV transmission is approximately 1%. Thus, ARV prophylaxis with full suppression of HIV RNA is recommended for all pregnant women with HIV infection, regardless of HIV viral load. Note that ART may exert protective effects not only by lowering maternal HIV RNA but also (for ARVs with good transplacental passage) by providing preexposure and postexposure prophylaxis.
Other maternal factors associated with increased risk of perinatal transmission include low CD4 cell count, sexually transmitted infections, active genital herpes during labor, illicit drug use, cigarette smoking, and unprotected sex with multiple partners.
Obstetric factors also affect the risk of HIV transmission. Infection risk increases linearly with the increased duration of ruptured membranes, although the effect of ruptured membranes in women with low viral loads is not known. Invasive procedures performed at any time during pregnancy, such as amniocentesis, placement of scalp electrodes, artificial rupture of membranes, episiotomy, or operative (forceps) delivery may increase risk by exposing the fetus to maternal blood; these procedures should be avoided (though the risk of transmission in women on fully suppressive ART is not clear). In addition, the mode of delivery, whether vaginal or cesarean, can influence the risk of HIV transmission. Scheduled cesarean delivery decreases the rate of perinatal infection for women with an HIV RNA level of >1,000 copies/mL, but its efficacy is not clear for women whose labor has begun or for those whose membranes have ruptured; see "Intrapartum Management and Mode of Delivery," below, for further information.
Infant risk factors for HIV infection include premature birth, low birth weight, skin and mucous membrane lesions such as thrush, and breast-feeding. Breast-feeding increases the risk of HIV transmission by 5-20%. In the United States, where safe, affordable replacement feeding and clean water routinely are available, women with HIV should not breast-feed. However, some women with HIV will be under tremendous cultural and familial pressure to breast-feed and will need the clinician's ongoing support to use substitute formula.
Because many factors that affect the risk of perinatal HIV transmission may be modified, clinicians should educate pregnant women carefully about the importance of ARV prophylaxis and other strategies to reduce the risk of maternal-fetal transmission of HIV.
The goals of ART for the pregnant woman are the same as those for any person living with HIV:
An additional, and crucial, goal of ART for pregnant women is to reduce the risk of perinatal HIV transmission through maximal HIV suppression. The DHHS recommendations discuss in detail the multiple issues that must be considered when balancing the woman's need for therapy for her own health and the need to decrease the risk of transmission to the infant. Combination ART is recommended for all HIV-infected pregnant women regardless of CD4 count or HIV viral load. Decisions about ART are complex and should be made by the woman and her health care provider after discussing the risks and benefits. Clinicians are urged to consult an HIV specialist and the most current DHHS recommendations when making therapeutic decisions. The Perinatal HIV Hotline (888-448-8765) provides free clinical consultation on all aspects of perinatal HIV care. The following discussion addresses some of the issues in determining ART strategies and is taken from the DHHS Perinatal ARV Guidelines.
The DHHS Perinatal HIV Guidelines Working Group recommends fully suppressive combination ART for all pregnant women, unless there are compelling reasons based on pregnancy-specific maternal and fetal safety issues to modify this approach. Key recommendations from the DHHS Perinatal ARV Guidelines include the following:
A fundamental principle of the guidelines is that therapies of known benefit should not be withheld during pregnancy unless they may cause adverse effects to the woman, fetus, or infant, and these adverse effects outweigh the potential benefits. Thus, women should be advised of the potential risks and benefits of ART (to the woman, fetus, and infant) and of the limited long-term data on outcomes for infants with in utero exposure to ARVs, but treatment decisions should be guided by the woman's clinical, virologic, and immunologic status and by the goal of preventing perinatal transmission. Women should be educated and counseled on the importance of close adherence to the ART regimen (see chapter Adherence).
Drug-resistance testing should be conducted for all pregnant women before the initiation of therapy, and for women who are already on ART without fully suppressed HIV RNA.
All women receiving ARVs during pregnancy for prophylaxis or for treatment should receive a combination containing at least three agents, with the aim of viral suppression to undetectable levels (i.e., <40-75 copies/mL, depending on the assay). Monotherapy (e.g., with ZDV) and dual therapy are not as effective and generally are not recommended. The regimen should include two nucleoside reverse transcriptase inhibitors (NRTIs) and either a nonnucleoside reverse transcriptase inhibitors (NNRTI) or a protease inhibitor (PI). Regimen selection should be individualized on the basis of factors such as anticipated safety and efficacy, ARV history, results of resistance testing, and comorbidities (e.g., hepatitis B virus [HBV]) (see chapter Antiretroviral Therapy for considerations in selecting ARVs). It should be recognized that only limited information is available for many ARVs and ARV combinations regarding potential toxicities for the fetus or infant (see Table 4 of the Guidelines), and for dosage requirements with pregnant women.
The DHHS Perinatal ARV Guidelines offer recommendations on the use of specific ARV agents during pregnancy. The table below shows "recommended" and "alternative" ARVs; others are classified as "Use in special circumstances" or "Insufficient data to recommend use." For more complete information, see Table 5 of the Guidelines).
|ARV Class||Recommended Agents||Alternative Agents|
The guidelines' preferred NRTI component is ZDV/3TC, because of data showing safety and efficacy in pregnancy. The specific alternative NRTIs listed above may be used for women with severe intolerance to ZDV (e.g., severe anemia) or documented resistance to ZDV (see "Safety and Toxicity of Antiretroviral Medications During Pregnancy," below).
Of the NNRTIs, nevirapine may be used for women with CD4 counts of <250 cells/µL or continued for women who are already on nevirapine-containing regimens. Nevirapine generally should not be used for treatment-naive women with CD4 counts of >250 cells/µL because of an increased risk of symptomatic and potentially fatal hepatic and rash toxicity. Efavirenz is not recommended for use during the first trimester because of potential teratogenicity, but it can be considered in later stages of pregnancy if other agents are not appropriate (see "Safety and Toxicity of Antiretroviral Medications During Pregnancy," below). There are insufficient pharmacokinetic and safety data to recommend the use of etravirine during pregnancy.
Lopinavir/ritonavir is the recommended PI based on efficacy studies in adults and experience in pregnant women. Alternative PIs include ritonavir-boosted atazanavir, saquinavir, and indinavir, although data during pregnancy are limited and the latter two agents may be less well tolerated. Nelfinavir, another alternative agent, has been used widely for pregnant women but generally is not recommended for nonpregnant adults because of inferior efficacy compared with first-line agents. Darunavir, fosamprenavir, and tipranavir are not recommended because of lack of data in pregnancy, but they may be considered if other agents are not tolerated or are not appropriate.
Pharmacokinetic and safety data in pregnancy are not sufficient to recommend the use of raltegravir, maraviroc, or enfuvirtide, but these may be considered for use by women for whom drugs in other classes have failed; they should be prescribed in consultation with HIV and obstetric specialists.
Some key recommendations of the DHHS guidelines are that ZDV should be included in the ARV regimen if possible, that the ZDV prophylaxis regimen used in PACTG 076 should be administered intrapartum (i.e., IV ZDV during labor), and that PO ZDV should be given to newborns for 6 weeks. The guidelines emphasize that the PACTG 076 regimen is effective not only for women whose clinical status is similar to that of the participants in the original study, but also for women with advanced HIV disease, low CD4 counts, and previous ZDV therapy.
The DHHS Perinatal ARV Guidelines offer recommendations on ARV prophylaxis to reduce perinatal HIV transmission based on four clinical scenarios, categorized by whether the mother needs ART for her own health and by her ART status when she presents for care (see Table 6 of the Guidelines).
Women already receiving ART should, in general, continue to receive it during pregnancy if it is suppressing viral replication. If the woman has detectable virus (e.g., >500-1,000 copies/mL) on therapy, HIV drug-resistance testing should be performed, and the regimen should be optimized to maximize the likelihood of achieving virologic suppression. Women presenting in the first trimester should be counseled about the risks and benefits of ART during this period. Discontinuation of therapy could lead to increased viral load and potential for transmission to the fetus.
Efavirenz should be avoided or be substituted for in the first trimester. Pregnant women receiving nevirapine-containing regimens should continue them, regardless of CD4 count, if they are virologically suppressed and tolerating the regimen.
Any pregnant woman who meets the standard criteria for ART under the DHHS guidelines for adults and adolescents should receive standard, potent, combination ART as soon as possible, including during the first trimester. The drug regimen should be based on the recommendations of the Perinatal ARV Guidelines (see above and Table 5 of the Guidelines). As in other scenarios, drug-resistance testing should guide ARV selection. Efavirenz should be avoided during the first trimester.
ART is recommended as perinatal prophylaxis with pregnant women for whom treatment is not required for their own health. This recommendation applies to all pregnant women regardless of viral load. Rates of transmission are very low among women with undetectable or low viral loads (<1,000 copies/mL) but transmission has occurred at all RNA levels. ARV medications decrease the risk of transmission, including in women with low viral loads. Antenatal ART not only lowers maternal viral load but also provides the infant with preexposure prophylaxis during the birth process; the neonate also receives postexposure prophylaxis through neonatal ZDV.
Women should be counseled about the benefits of ART in preventing perinatal transmission. Because the risk of teratogenic effects on the fetus is greatest during the first 10 weeks of gestation, the woman may wish to defer starting a regimen until after 12 weeks' gestation. As discussed above, efavirenz should be avoided during the first trimester.
Consideration can be given to discontinuing ART in women who do not have indications for continued ART; see "Postpartum Follow-Up of HIV-Infected Women," below.
In some instances, a pregnant woman has been on ART for prophylaxis during a previous pregnancy and subsequently discontinued the medication. ARV drug-resistance testing should be conducted prior to initiating ART. The regimen should be chosen on the basis of previous ART experience and the reasons for stopping and results of past and current resistance testing, with avoidance of drugs and combinations with teratogenic (e.g., efavirenz ) or adverse maternal effects. The selection of an ART regimen for women with advanced HIV disease or a history of extensive prior therapy can be challenging, and consultation with an HIV specialist is recommended. As discussed above, efavirenz should be avoided during the first trimester.
Physiologic changes that occur during pregnancy (e.g., prolonged gastrointestinal transit time, increase in body fat and water, and changes in cardiac, circulatory, hepatic, and renal function) may affect the kinetics of drug absorption, distribution, and elimination. Few pharmacokinetic studies have been conducted on levels of ARVs during pregnancy, but available data suggest that altered dosing for some PIs (e.g., lopinavir/ritonavir) may be required (see Table 5 of the Guidelines).
In selecting ARVs, providers must decide whether to concurrently treat HBV, using NRTIs that have activity against both HIV and HBV (i.e., lamivudine, emtricitabine, and tenofovir). Making these decisions is complicated, and consultation with an expert is recommended. Also see the relevant discussion in the DHHS Perinatal ARV Guidelines, and chapter Hepatitis B Infection in this manual.
HBV-infected pregnant women who are not immune to hepatitis A should be vaccinated. Infants born to coinfected women should receive HBV immune globulin and start the HBV vaccine series within 12 hours after birth (with subsequent vaccine doses per usual protocol).
Treatment for hepatitis C (HCV) is not recommended during pregnancy. Recommendations for ART during pregnancy are the same for women who are coinfected with HCV as for those without HCV coinfection.
Coninfected pregnant women should be tested for immunity to hepatitis A and HBV; if not immune, they should be vaccinated. Infants born to coinfected women should be evaluated for HCV infection.
See the relevant discussion in the DHHS Perinatal ARV Guidelines, and chapter Hepatitis C Infection in this manual.
Limited data are available on the safety of ARVs in pregnancy, particularly when ARVs are used in combination. The existing safety and toxicity information is derived from animal and human studies, clinical trials, registry data, and anecdotal experience.
Several drugs are of special concern when used during pregnancy (see DHHS Perinatal ARV Guidelines; Table 4), including the following:
In addition, PIs have been associated with an increased risk of new-onset diabetes, worsening diabetes, and diabetic ketoacidosis. Of course, pregnancy itself is a risk factor for hyperglycemia. Clinicians should monitor the glucose levels of pregnant women taking PIs and should educate them about the symptoms of hyperglycemia. The DHHS Perinatal ARV Guidelines recommend that pregnant women on ART should be screened with a standard 50 g glucose loading test at 24-28 weeks (see chapter Care of HIV-Infected Pregnant Women).
Information on ARV toxicity during pregnancy should be consulted carefully before treatment choices are made. The DHHS guidelines provide information on each ARV drug, including preclinical and clinical data, pharmacokinetic and toxicity data, and recommendations regarding use during pregnancy. These guidelines are updated routinely as information is received (see Tables 4 and 5 of the Guidelines). Numerous other medications also are contraindicated for use during pregnancy, and potential toxicity should be considered carefully before any medication is given to a pregnant woman.
A European study found an approximately twofold increase in risk of preterm birth among mothers who took combination therapy during pregnancy (whether started before or during pregnancy). A metaanalysis of seven clinical trials in the United States, however, found that ARV use was not associated with preterm labor, low birth-weight, low Apgar scores, or stillbirth. Subsequent data have been conflicting, but clinicians should be aware of a possible small increased risk of preterm birth among women who receive PIs. However, the benefit of PIs for the mother's health and for prevention of perinatal transmission is clear, and PIs should not be withheld. Until more is known, pregnant women who are taking combination regimens should be monitored closely for complications and toxicities and should be educated about the signs of premature labor.
The Antiretroviral Pregnancy Registry collects observational data on HIV-infected pregnant women taking ARV medications to determine whether patterns of fetal or neonatal abnormalities occur. This is a project initiated by the pharmaceutical industry and overseen by an advisory committee comprising representatives from the CDC, National Institutes of Health, FDA, pediatric and obstetric providers, and others. Providers who care for pregnant women taking ARVs are encouraged to enroll patients in the registry at the time of initial evaluation. Information is confidential and patients' names are not used. More information can be obtained by visiting the registry website or by calling 800-258-4263, 8:30 a.m. to 5:30 p.m. eastern time.
All pregnant women with HIV infection should receive the intrapartum and neonatal components of ZDV prophylaxis used in the PACTG 076 protocol, as outlined earlier. IV ZDV should be given to the woman during labor as a 1-hour loading dose of 2 mg/kg followed by a continuous infusion of 1 mg/kg per hour until delivery. Women on ART should continue their regimen on schedule as much as possible during labor, except that women receiving ZDV or a ZDV-containing fixed-dose combination should be given IV ZDV, with other components continued PO. For women on a stavudine-containing regimen, the stavudine component should be discontinued while IV ZDV is being administered.
For women who have detectable viral load at the time of delivery, the addition of the single-dose nevirapine protocol (single dose to the woman during labor, single dose to the neonate) generally is not recommended in the United States, because clinical trials conducted to date, although small, have not shown benefit and there is a risk of nevirapine resistance. However, single-dose nevirapine may be considered in special circumstances for women with high HIV RNA levels, especially when a patient is not on ART and delivery is vaginal rather than via a scheduled cesarean delivery. If single-dose nevirapine is given, most specialists recommend also giving NRTIs (e.g., ZDV/3TC), and continuing the NRTIs for at least 7 days to decrease the risk of nevirapine resistance.
Studies conducted before the availability of viral load testing found that cesarean delivery performed before the onset of labor or rupture of membranes significantly reduced the risk of perinatal transmission. However, now that many HIV-infected pregnant women in the United States and other high-income settings are receiving potent combination ART, rates of HIV transmission rates are very low (about 1.2-1.5%, unadjusted for mode of delivery); it is difficult to determine whether delivery by cesarean section further decreases the risk of peripartum transmission.
For a woman with a viral load of <1,000 copies/mL, the decisions on mode of delivery should be individualized and based on discussions between the woman and her obstetric clinician. The woman and her health care providers should decide about mode of delivery before the onset of labor, based on her current viral load, her health status, and the outcome of discussions about other concerns, which should include counseling about the risks and benefits of cesarean delivery. For women with HIV RNA levels of >1,000 copies/mL at or near the time of delivery (this would apply to many women on ART for whom viral suppression has not been achieved by the time of delivery because of late entry into care, issues of adherence, or viral resistance), the DHHS Perinatal ARV Guidelines and the American College of Obstetricians and Gynecologists recommend delivery by scheduled cesarean section at 38 weeks' gestation. IV ZDV should be started 3 hours before a scheduled cesarean delivery. Prophylactic antibiotics are recommended at the time of cesarean delivery for HIV-infected women to decrease the risk of maternal infection.
It is not clear whether cesarean delivery provides any benefits in preventing perinatal HIV transmission once labor has begun or membranes are ruptured. Management of a woman for whom a scheduled cesarean was planned but who presents in labor or with ruptured membranes should be individualized on the basis of her HIV viral load, current ART regimen, length of time since membrane rupture, duration of labor, and other clinical factors.
The DHHS Perinatal ARV Guidelines outline four scenarios in which the clinician must decide whether cesarean delivery is needed (see Table 9 of the Guidelines). The data on the benefits of cesarean delivery are complex and must be considered alongside the increased risk to the mother after surgery. The clinician should consult an obstetric/HIV specialist to discuss specific situations.
A woman who presents in labor without a documented HIV status should receive a rapid HIV antibody test and, if the result is positive, should be presumed to be infected until the confirmatory HIV test result is received. She should receive IV ZDV immediately to prevent perinatal transmission. She will need confirmation and staging of her HIV infection (e.g., CD4 cell count, HIV RNA viral load) as well as referral to care for her own health and ongoing psychological support.
Questions remain about the management of labor when a vaginal delivery is planned. Because the duration of ruptured membranes is a risk factor for perinatal transmission, pregnant women with HIV infection should be counseled to go to a hospital for care at the first signs of labor or rupture of membranes. If the membranes rupture spontaneously before labor occurs or early in labor, the clinician should consider interventions to decrease the interval to delivery, such as administration of oxytocin. Procedures that potentially increase the neonate's exposure to maternal blood, such as the use of scalp electrodes or artificial rupture of membranes, should be avoided. Operative interventions with forceps or vacuum extractor and episiotomy should be performed only in select circumstances.
For management of postpartum hemorrhage owing to uterine atony, note that methergine has significant interactions with PIs and with efavirenz and should not be administered to women taking these medications, if possible. If alternative treatments are not available and methergine must be used, it should be given at the lowest possible low dosage and for the shortest duration possible.
Women with HIV infection who have recently delivered need access to a comprehensive array of services for themselves and their infants. The clinician should refer the postpartum woman not only to her primary obstetric and HIV providers for family planning and HIV management but also to a pediatric HIV specialist for care of her infant. She should be referred as needed for mental health, substance abuse, and social support services. The clinician should be alert for indications of postpartum depression and should offer treatment promptly, if indicated. Adherence to ARV regimens may be particularly difficult for a woman in the immediate postpartum period because of postpartum physical and psychological changes and the demands of caring for a newborn; accordingly, the woman may require new or continued support services.
Women who are diagnosed through preliminary rapid HIV testing in labor will need thorough evaluation and management including confirmatory HIV testing and referral for medical and social services. They should not breast-feed unless the results of the confirmatory tests are received as negative.
Women should be evaluated regarding their ongoing need for ART postpartum. If ART was given only or primarily to reduce the risk of perinatal transmission, and if the woman's CD4 count has always been above the threshold recommended for treatment in the current adult and adolescent guidelines and she does not have other factors that would recommend treatment, the woman and her clinician, in consultation with an HIV specialist, may consider discontinuing therapy after pregnancy, with the option to resume ART in the future. On the other hand, for women with a CD4 nadir below the currently recommended threshold for treatment initiation or a history of symptoms or conditions caused by HIV, long-term ART should be recommended.
If ART is being discontinued, all drugs should be stopped at the same time if they have similar half-lives. NNRTIs have longer half lives than other agents, so a NNRTI should be discontinued at least 7 days before other ARVs, in order to avoid a period of NNRTI monotherapy and the development of NNRTI resistance mutations. Alternatively, a PI may be substituted for the NNRTI several weeks before stopping the ART. Note that, for women with HBV coinfection, discontinuation of NRTIs with anti-HBV activity (e.g., 3TC, emtricitabine, tenofovir) may result in a flare of HBV; consult with an expert before discontinuing ART.
Contraceptive counseling is an important aspect of postpartum care. Women should be offered dual-method contraception if pregnancy is not desired in the short-term future or if the ART regimen contains potentially teratogenic drugs such as efavirenz. (See chapters Care of HIV-Infected Pregnant Women and Health Care of HIV-Infected Women Through the Life Cycle.)
Breast-feeding is not recommended in the United States or other parts of the world where replacement feeding is affordable, feasible, acceptable, sustainable, and safe. Women may experience culture-based and family pressure to breast-feed and may need support to use replacement feeding.
The HIV-exposed neonate born to a mother with HIV infection should receive ZDV syrup at a dosage of 2 mg/kg body weight per dose Q6H beginning as soon as possible after birth, preferably within 6-12 hours, and continuing for 6 weeks. Newborns should be discharged home with a supply of PO ZDV syrup. The use of ZDV for the neonate is recommended regardless of whether the mother has a history of resistance to ZDV. Few data are available to guide decision making regarding the use of additional ARVs (i.e., combination therapy) for neonates; consult with a pediatric HIV expert. Every HIV-exposed infant should be referred to a pediatric HIV specialist for diagnostic testing and monitoring of health status.
For an infant born to a mother whose HIV status is unknown, rapid HIV testing of the mother or the infant should be done as soon as possible. If the result for either is positive, ZDV prophylaxis for the infant should be started immediately. A confirmatory HIV test (e.g., Western blot) should be done at the same time and prophylaxis should be discontinued if the result is negative. If positive, the infant should be tested with an HIV DNA polymerase chain reaction (PCR) assay or an HIV RNA assay. If the newborn's HIV viral load test result is positive, prophylaxis should be discontinued and the infant should be referred urgently to a pediatric HIV specialist for management of HIV infection using combination ART.
Traditional HIV antibody testing cannot be used with infants because maternal antibodies may persist for up to 18 months. Diagnosis of HIV infection in infants requires virologic testing (HIV DNA or HIV RNA). Virologic testing should be performed by age 14-21 days, then at 1-2 months, and at 4-6 months. HIV can be diagnosed in an infant on the basis of two positive results from virologic tests done on separate blood samples at any time. HIV can be excluded presumptively in an infant with two or more negative results from virologic tests, with one done at ≥14 days of age and one done at ≥1 month of age, or one negative virologic test done result done at ≥2 months of age, or one negative HIV antibody test result done at ≥6 months of age. HIV can be excluded definitively with two or more negative virologic tests, one done at age ≥1 month and one done at ≥4 months, or two negative HIV antibody tests from separate specimens done at age ≥6 months. However these tests may not be accurate in infants who are receiving combination ART. Some experts recommend retesting, using an antibody test, at age 12-18 months as a confirmatory test.
Infants should have a baseline complete blood count and should be monitored for anemia while they are taking ZDV. Pneumocystis jiroveci pneumonia (PCP) prophylaxis for HIV-exposed infants is recommended for infants with indeterminate HIV status starting at 6 weeks when the ZDV prophylaxis regimen is completed until they are determined to presumptively or definitively HIV seronegative. Initiation of PCP prophylaxis should be stopped or avoided altogether when HIV has been presumptively excluded.
Parents and family caregivers must be taught how to monitor the infant for signs of illness until an HIV diagnosis is made or ruled out. They also need to know that the infant's exposure to ARV agents in utero is an important part of the infant's medical history and should be shared with future health care providers. Although no enduring consequences of ARV exposure have been confirmed, the child may be at risk of long-term problems.