Recommendations usually are followed by levels of evidence (I–III) identifying the type of supporting evidence and strength of recommendation grades (A–C). Definitions for these are presented at the end of the "Major Recommendations" field.
Note from the Department of Health and Human Services (DHHS), Centers for Disease Control and Prevention (CDC) and the National Guideline Clearinghouse (NGC): Key changes made to update the September 14, 2011, version of the guidelines are summarized below.
- Lessons from Clinical Trials of Antiretroviral Interventions to Reduce Perinatal Transmission of Human Immunodeficiency Virus (HIV) and Table 3, Results of Major Studies on Antiretroviral Prophylaxis to Prevent Mother-to-Child Transmission of HIV:
- Table 3 updated to include data on 48-week results of the Breastfeeding and Nutrition (BAN) study in Malawi.
- Preconception Counseling and Care for HIV-Infected Women of Childbearing Age and Table 4, Drug Interactions between Hormonal Contraceptives and Antiretroviral Agents:
- Table 4 updated to include data on hormonal contraceptive interactions with rilpivirine and raltegravir.
- Reproductive Options for HIV-Concordant and Serodiscordant Couples:
- For serodiscordant couples who want to conceive, use of antiretroviral therapy is now recommended for the HIV-infected partner, with the strength of the recommendation differing based on the CD4-cell count of the infected partner.
- Added discussion of the pre-exposure prophylaxis (PrEP) studies in heterosexual couples, with a new recommendation regarding PrEP in discordant couples who wish to conceive. Discussion includes information on counseling, laboratory testing, and monitoring of individuals on PrEP and importance of reporting uninfected women who become pregnant on PrEP to the Antiretroviral Pregnancy Registry.
- Antepartum Care:
- General Principles Regarding Use of Antiretroviral Drugs during Pregnancy:
- Initial assessment for HIV-infected pregnant women expanded to include screening for hepatitis C virus and tuberculosis infection, as well as history of side effects or toxicities from prior antiretroviral drug regimens.
- Additional benefit of antiretroviral drug regimens expanded to include benefits of therapy for reducing sexual transmission to discordant partners when viral suppression is maintained, with discussion of the HPTN 052 trial results.
- Recommendations for Use of Antiretroviral Drugs during Pregnancy and Table 5, Antiretroviral Drug Use in Pregnant HIV-Infected Women: Pharmacokinetic and Toxicity Data in Human Pregnancy and Recommendations for Use in Pregnancy:
- Modified recommendations regarding categorization of various antiretroviral agents in categories of drugs that are preferred, alternative, or use in special circumstance.
- Nucleoside reverse transcriptase inhibitors
- Protease inhibitors
- Integrase inhibitors
- HIV-Infected Pregnant Women Who Have Never Received Antiretroviral Drugs (Antiretroviral Naive):
- Increased discussion on when to initiate an antiretroviral drug regimen in pregnant women.
- HIV-Infected Pregnant Women Who Are Currently Receiving Antiretroviral Therapy:
- Discussion of efavirenz use in the first trimester.
- Special Situations - Failure of Viral Suppression:
- Use of raltegravir in late pregnancy in women with high viral loads to decrease viral load discussed but not endorsed. The efficacy and safety of this approach have not been evaluated and only anecdotal reports are available. In the setting of a failing regimen related to nonadherence and/or resistance, there are concerns that the addition of a single agent may further increase risk of resistance and potential loss of future effectiveness with raltegravir. Until more data become available on the safety of raltegravir use in pregnancy, this approach cannot be recommended.
- Special Considerations Regarding the Use of Antiretroviral Drugs by HIV-Infected Pregnant Women and Their Infants:
- Combination Antiretroviral Drug Regimens and Pregnancy Outcome:
- Addition of a new table—Table 7—Results of Studies Assessing Association Between Antiretroviral Regimens and Preterm Delivery—that summarizes the results of studies assessing the association between antiretroviral regimens and preterm delivery.
- Intrapartum Care:
- Intrapartum Antiretroviral Therapy/Prophylaxis:
- Discussion of use of intravenous (IV) zidovudine during labor and maternal viral load.
- Postpartum Care:
- Infant Antiretroviral Prophylaxis and Table 9, Recommended Neonatal Dosing for Prevention of Mother-to-Child Transmission of HIV:
- Table 9 revised to reflect neonatal dosing only of zidovudine (in term and preterm infants) and nevirapine in the regimen used in the NICHD-HPTN 040 study.
- Choice of neonatal antiretroviral drug prophylaxis includes discussion of the NICHD-HPTN 040 study and concerns regarding use of lopinavir/ritonavir in neonates.
- Addition of new pharmacokinetic data on nevirapine in preterm infants.
- Initial Postnatal Management of the HIV-Exposed Neonate
Lessons from Clinical Trials of Antiretroviral Interventions to Reduce Perinatal Transmission of HIV
Mechanisms of Action of Antiretroviral Prophylaxis in Reducing Perinatal Transmission of HIV
- Antiretroviral (ARV) drugs reduce perinatal transmission by several mechanisms, including lowering maternal antepartum viral load and providing infant pre- and post-exposure prophylaxis. Therefore, combined antepartum, intrapartum, and infant ARV prophylaxis is recommended to prevent perinatal transmission of HIV (AI).
Lessons from International Clinical Trials of Short-Course Antiretroviral Regimens for Prevention of Perinatal Transmission of HIV
A number of regimens have been identified that are effective in reducing perinatal transmission in resource-limited countries (see Table 3 in the original guideline document). In many cases, direct comparison of results from trials of these regimens is not possible because the studies involved diverse patient populations residing in different geographic locations, infected with diverse viral subtypes, and with different infant feeding practices. However, some generalizations are relevant to understanding use of ARV drugs for prevention of perinatal transmission in both resource-limited and resource-rich countries.
- Combination antenatal prophylaxis taken over a longer duration is more effective than a short-course single-drug regimen in reducing perinatal transmission.
- Combination infant ARV prophylaxis is recommended in the United States for infants whose mothers have not received antenatal ARV drugs.
- Adding single-dose intrapartum nevirapine is not recommended for women in the United States who are receiving standard recommended antenatal ARV prophylaxis.
- Breastfeeding by HIV-infected women is not recommended in the United States.
See the original guideline document for further discussion of this topic.
Perinatal Transmission of HIV and Maternal HIV RNA Copy Number
- All HIV-infected pregnant women should be counseled about and administered ARV drugs during pregnancy for prevention of perinatal transmission, regardless of their HIV ribonucleic acid (RNA) levels (AI).
Preconception Counseling and Care for HIV-Infected Women of Childbearing Age
- Discuss childbearing intentions with all women of childbearing age on an ongoing basis throughout the course of their care (AIII).
- Include information about effective and appropriate contraceptive methods to reduce the likelihood of unintended pregnancy (AI).
- During preconception counseling, include information on safer sexual practices and elimination of use of alcohol, illicit drugs, and smoking, which are important for the health of all women as well as for fetal/infant health, should pregnancy occur (AII).
- When evaluating HIV-infected women, include assessment of HIV disease status and need for antiretroviral therapy (ART) for their own health (AII).
- Choose an ART regimen for HIV-infected women of childbearing age based on consideration of effectiveness for treatment of maternal disease, hepatitis B virus disease status, teratogenic potential of the drugs in the regimen should pregnancy occur, and possible adverse outcomes for mother and fetus (AII).
The Centers for Disease Control and Prevention (CDC), the American College of Obstetrics and Gynecology (ACOG), and other national organizations recommend offering all women of childbearing age comprehensive family planning and the opportunity to receive preconception counseling and care as a component of routine primary medical care. The purpose of preconception care is to improve the health of each woman prior to conception by identifying risk factors for adverse maternal or fetal outcome, providing education and counseling targeted to the patient's individual needs, and treating or stabilizing medical conditions to optimize maternal and fetal outcomes. Preconception care is not a single clinical visit but rather a process of ongoing care and interventions integrated into primary care to address the needs of women during the different stages of reproductive life. Because more than half of all pregnancies in the United States are unintended, it is important that comprehensive family planning and preconception care be integrated into routine health visits. Providers should initiate and document a nonjudgmental conversation with all women of reproductive age concerning their reproductive desires because women may be reluctant to bring this up themselves. HIV care providers who routinely care for women of reproductive age play an important role in promoting preconception health and informed reproductive decisions.
The fundamental principles of preconception counseling and care are outlined in the CDC Preconception Care Work Group's Recommendations to Improve Preconception Health and Health Care . In addition to the general components of preconception counseling and care that are appropriate for all women of reproductive age, HIV-infected women have specific needs that should be addressed. Because many women infected with HIV are aware of their HIV status before becoming pregnant, issues that impact pregnancy may be addressed before conception during their routine medical care for HIV disease. In addition to the principles outlined by the CDC Preconception Care Work Group, the following components of preconception counseling and care are specifically recommended for HIV-infected women. Health care providers should:
- Discuss reproductive options, actively assess women's pregnancy intentions on an ongoing basis throughout the course of care and, when appropriate, make referrals to experts in HIV and women's health, including experts in reproductive endocrinology and infertility when necessary.
- Offer all women effective and appropriate contraceptive methods to reduce the likelihood of unintended pregnancy. Providers should be aware of potential interactions between ARV drugs and hormonal contraceptives that could lower contraceptive efficacy (see Table 4 in the original guideline document).
- Counsel on safe sexual practices that prevent HIV transmission to sexual partners, protect women from acquiring sexually transmitted diseases, and reduce the potential to acquire more virulent or resistant strains of HIV.
- Counsel on eliminating alcohol, illicit drug use, and cigarette smoking.
- Educate and counsel women about risk factors for perinatal transmission of HIV, strategies to reduce those risks, potential effects of HIV or of ARV drugs given either for treatment or solely for prevention of mother-to-child transmission (MTCT) on pregnancy course and outcomes, and the recommendation that HIV-infected women in the United States not breastfeed because of the risk of transmission of HIV and the availability of safe and sustainable infant feeding alternatives.
- When prescribing ART to women of childbearing age, consider the regimen's effectiveness for treatment of HIV, an individual's hepatitis B disease status, the drugs' potential for teratogenicity should pregnancy occur, and possible adverse outcomes for mother and fetus.
- Use the preconception period in women who are contemplating pregnancy to adjust ARV regimens to exclude efavirenz or other drugs with teratogenic potential.
- Make a primary treatment goal for women who are on ART for their own health and who want to get pregnant the attainment of a stable, maximally suppressed maternal viral load prior to conception to decrease the risk of MTCT.
- Evaluate and appropriately manage therapy-associated side effects such as hyperglycemia, anemia, and hepatotoxicity that may adversely impact maternal-fetal health outcomes.
- Evaluate the need for appropriate prophylaxis or treatment for opportunistic infections, including safety, tolerability, and potential toxicity of specific agents when used in pregnancy.
- Administer medical immunizations for influenza, pneumococcal or hepatitis A and B vaccines, and other vaccines as indicated (see http://www.cdc.gov/vaccines/acip/committee/guidance/rec-vac-preg.html ).
- Encourage sexual partners to receive HIV testing and, if infected, to seek counseling and appropriate HIV care.
Reproductive Options for HIV-Concordant and Serodiscordant Couples
- For serodiscordant couples who want to conceive, expert consultation is recommended so that approaches can be tailored to specific needs, which may vary from couple to couple (AIII). It is important to recognize that treatment of the infected partner may not be fully protective against sexual transmission of HIV.
- Partners should be screened and treated for genital tract infections before attempting to conceive (AII).
- For HIV-infected females with HIV-uninfected male partners, the safest conception option is artificial insemination, including the option of self-insemination with her partner's sperm during the peri-ovulatory period (AIII).
- For HIV-infected men with an HIV-uninfected female partner, the use of sperm preparation techniques coupled with either intrauterine insemination or in vitro fertilization should be considered if using donor sperm from an HIV-uninfected male for insemination is unacceptable (AII).
- For serodiscordant couples who wish to conceive, initiation of ART for the HIV-infected partner is recommended (AI for CD4 T-lymphocyte [CD4-cell] count ≤550 cells/mm3, BIII for CD4-cell count >550 cells/mm3). If therapy is initiated, maximal viral suppression is recommended before conception is attempted (AIII).
- Periconception administration of antiretroviral PrEP for HIV-uninfected partners may offer an additional tool to reduce the risk of sexual transmission (CIII). The utility of PrEP of the uninfected partner when the infected partner is receiving ART has not been studied.
Monitoring of HIV-Uninfected Pregnant Women with a Partner Known to Be HIV Infected
Clinicians may increasingly be seeing HIV-uninfected women who present during pregnancy and indicate that their partners are HIV infected. They, like all pregnant women, should be notified that HIV screening is recommended and they will receive an HIV test as part of the routine panel of prenatal tests unless they decline. These women also should receive a second HIV test during the third trimester, preferably before 36 weeks of gestation, as is recommended for high-risk women. Furthermore, pregnant women who present in labor without results of third-trimester testing should be screened with a rapid HIV test on the labor and delivery unit. If at any time during pregnancy a clinician suspects that a pregnant woman may be in the "window" period of seroconversion (that is, she has signs or symptoms consistent with acute HIV infection), then a plasma HIV RNA test should be used in conjunction with an HIV antibody test. If the plasma HIV RNA is negative, it should be repeated in 2 weeks. All HIV-uninfected pregnant women with HIV-infected partners should always use condoms during sexual intercourse to prevent acquisition of HIV. Women should be counseled regarding the symptoms of acute retroviral syndrome (that is, fever, pharyngitis, rash, myalgia, arthralgia, diarrhea, headache) and the importance of seeking medical care and testing if they experience such symptoms.
Women who test positive on either conventional or rapid HIV tests should receive appropriate evaluation and interventions to reduce perinatal transmission of HIV, including immediate initiation of appropriate ARV prophylaxis and consideration of elective cesarean delivery according to established guidelines (see "Transmission and Mode of Delivery," below). In cases where confirmatory testing results are not readily available, such as with rapid testing during labor, it is still appropriate to initiate interventions to reduce perinatal transmission (see "Infant Antiretroviral Prophylaxis," below).
Women with HIV-infected partners who test HIV negative should continue to be regularly counseled regarding consistent condom use to decrease their risk of sexual transmission of HIV. Women with primary HIV infection during pregnancy or lactation are at high risk of transmitting HIV to their infants.
General Principles Regarding Use of Antiretroviral Drugs during Pregnancy
- Initial evaluation of infected pregnant women should include an assessment of HIV disease status and recommendations regarding initiation of ARV drugs or the need for any modification if currently receiving ART (AIII). The National Perinatal HIV Hotline (1-888-448-8765) provides free clinical consultation on all aspects of perinatal HIV care.
- Regardless of plasma HIV RNA copy number or CD4 T-lymphocyte cell count, all pregnant HIV-infected women should receive a combination ARV drug regimen antepartum to prevent perinatal transmission (AI). A combination regimen is recommended both for women who require therapy for their own health (AI) and for prevention of perinatal transmission in those who do not yet require therapy (AII).
- The known benefits and potential risks of ARV use during pregnancy should be discussed with all women (AIII).
- ARV drug-resistance studies should be performed before starting or modifying ARV drug regimens in women whose HIV RNA levels are above the threshold for resistance testing (that is, >500 to 1,000 copies/mL) (see "Antiretroviral Drug Resistance and Resistance Testing in Pregnancy," below) (AIII). When HIV is diagnosed later in pregnancy, ART or combination ARV prophylaxis should be initiated promptly without waiting for results of resistance testing (BIII).
- In counseling patients, the importance of adherence to the ARV regimen should be emphasized (AII).
- Considerations regarding continuing the ARV regimen for maternal treatment after delivery are the same as in nonpregnant individuals. The pros and cons of continuing versus discontinuing ARV drugs postpartum should be discussed with women so they can make educated decisions about postpartum ARV use before delivery (AIII). Those decisions should be made in consultation with the provider who will assume responsibility for the women's HIV care after delivery.
- Coordination of services among prenatal care providers, primary care and HIV specialty care providers, mental health and drug abuse treatment services, and public assistance programs is essential to ensure that infected women adhere to their ARV regimens (AIII).
In addition to the standard antenatal assessments for all pregnant women, the initial evaluation of those who are HIV infected should include assessment of HIV disease status and recommendations for HIV-related medical care. This initial assessment should include the following:
- Review of prior HIV-related illnesses and past CD4-cell counts and plasma HIV viral loads
- Current CD4-cell count
- Current plasma HIV RNA copy number
- Assessment of the need for prophylaxis against opportunistic infections such as Pneumocystis jirovecii pneumonia (PCP) or Mycobacterium avium complex (MAC) (see the NGC summary of the CDC's Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents)
- Screening for hepatitis C virus and tuberculosis in addition to standard screening for hepatitis B virus (HBV) infection
- Evaluation of immunization status per guidelines from the American College of Obstetricians and Gynecologists, with particular attention to hepatitis A, HBV, influenza, pneumococcus and tetanus, diphtheria, and pertussis (Tdap) immunizations
- Baseline complete blood cell count and renal and liver function testing
- Human leukocyte antigen (HLA)-B*5701 testing, if abacavir use is anticipated (see Table 5 in the original guideline document)
- History of prior and current ARV drug use, including prior ARV use for prevention of perinatal transmission or treatment of HIV and history of adherence problems
- Results of prior and current HIV ARV drug-resistance studies
- History of side effects or toxicities from prior ARV regimens
- Assessment of supportive care needs
ARV drugs for prevention of perinatal transmission of HIV are recommended for all pregnant women, regardless of CD4-cell counts and HIV RNA levels. In general, guidelines for the use of ART for the benefit of maternal health during pregnancy are the same as guidelines for women who are not pregnant, with some modifications, based on concerns about specific drugs and limited experience during pregnancy with newer drugs.
Decisions regarding initiation or modification of ARV drug regimens during pregnancy include considerations regarding the benefits and risks of ARV drug use that are common to all HIV-infected adults plus those unique to pregnancy. In general, the ARV drug combinations now available are more convenient and better tolerated than regimens used previously, resulting in greater efficacy and improved adherence. During pregnancy, maternal ARV toxicities must be considered, along with the potential impact of the ARV regimen on pregnancy outcome and on the fetuses and infants. Decisions about ARV drug regimens are further complicated because only limited data exist on the long-term maternal consequences of use of the agents during pregnancy solely for prophylaxis of transmission. Similarly, only limited data are available on the long-term consequences to infants of in utero exposure to ARVs.
The known benefits and known and unknown risks of ARV drug use during pregnancy should be considered and discussed with women (see "Special Considerations Regarding the Use of Antiretroviral Drugs by HIV-infected Pregnant Women and Their Infants," below). Results from preclinical and animal studies and available clinical information about use of the various agents during pregnancy also should be discussed (see "Supplement: Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy," in the original guideline document). Potential risks of these drugs should be placed into perspective by reviewing the substantial benefits of ARV drugs for maternal health and in reducing the risk of transmission of HIV to infants. Counseling of pregnant women about ARV use should be noncoercive, and providers should help women make informed decisions regarding use of ARV drugs.
Discussions with women about initiation of ARV drug regimens should include information about:
- Maternal risk for disease progression and the benefits and risks of initiation of therapy for maternal health
- Benefit of combination ARV regimens for preventing perinatal transmission of HIV
- Benefits of therapy for reducing sexual transmission to discordant partners when viral suppression is maintained
- Potential adverse effects of ARV drugs for mothers, fetuses, and infants, including potential interactions with other medications the women may already be receiving
- The limited long-term outcome data for both women who temporarily use ARV drugs during pregnancy for prophylaxis of transmission and infants with in utero exposure
- The need for strict adherence to the prescribed drug regimen to avoid resistance
Studies of zidovudine for the prevention of perinatal transmission suggest that an important mechanism of infant pre-exposure prophylaxis is transplacental drug passage. Thus, when selecting an ARV regimen for a pregnant woman, at least one nucleoside/nucleotide (NRTI) agent with high placental transfer should be included as a component of the dual NRTI backbone (see Table 5 in the original guideline document).
In women with plasma HIV RNA above the threshold for resistance testing (that is, >500–1,000 copies/mL), ARV drug-resistance studies should be performed before starting ARV drugs for maternal health or prophylaxis. When HIV is diagnosed later in pregnancy, however, ARV drugs should be initiated promptly without waiting for results of resistance testing (see "Antiretroviral Drug Resistance and Resistance Testing in Pregnancy," below).
Counseling should emphasize the importance of adherence to the ARV drug regimen. Support services, mental health services, and drug abuse treatment may be required, depending on women's individual circumstances. Coordination of services among prenatal care providers, primary care and HIV specialty care providers, mental health and drug abuse treatment services, and public assistance programs is essential to ensure that infected women adhere to their ARV drug regimens.
Providers should work with women to develop long-range plans regarding continuity of medical care and decisions about continuing ARV drugs postpartum. Considerations regarding postpartum continuation of the ARV regimen for maternal therapeutic indications are the same following delivery as for nonpregnant individuals. The impact on short- and long-term maternal health is unknown for postpartum discontinuation of combination ARV drug regimens used solely to prevent perinatal transmission. This is particularly important because women may have multiple pregnancies resulting in episodic receipt of ARV drugs. No increase in disease progression has been seen so far, however, in studies of pregnant women with relatively high CD4-cell counts who stop combination ARV drug regimens after delivery. The risks versus benefits of stopping ARV drug regimens postpartum in women with high CD4-cell counts are being evaluated in the ongoing PROMISE study (clinical trial number NCT00955968).
Current adult treatment guidelines strongly recommend ART for all individuals with CD4-cell counts <350 cells/mm3 based on randomized, controlled clinical trial data demonstrating a clear benefit in reduction of mortality and morbidity. Pregnant women with CD4 counts <350 cells/mm3 should begin ART as soon as possible during pregnancy and be counseled about the need to continue therapy after delivery and the importance of adherence to the regimen.
Based on observational cohort data and recent results from a randomized trial, the adult treatment guidelines also recommend initiating lifelong ART in individuals with CD4-cell counts between 350 and 500 cells/mm3. Observational studies suggest a relative decrease in mortality (although the overall number of events was small) and possibly a decrease in complications such as cardiovascular events with initiation of ART in this setting compared with waiting until CD4-cell counts drop below 350 cells/mm3.
Pregnant women with CD4-cell counts between 350 and 500 cells/mm3 should be started on a combination ARV regimen during pregnancy to prevent perinatal transmission of HIV and counseled about the current treatment recommendations, the potential risks versus benefits of stopping versus continuing the regimen after delivery (including reduction in transmission to discordant partners with continuing therapy when viral suppression is maintained), and the need for sustained strict adherence if the regimen is continued postpartum.
For individuals with CD4 counts >500 cells/mm3, the adult guidelines recommend initiating lifelong therapy as a moderate recommendation, given that data are incomplete on the clinical benefit of starting treatment at higher CD4-cell counts (>500 cells/mm3). So far, no increased risk of disease progression has been shown in studies of pregnant women with relatively high CD4 counts who stop ARV drugs after delivery. The potential benefits of early therapy must be weighed against possible drug toxicity, cost, and the risk of development of viral resistance with suboptimal adherence, which may be more likely postpartum. Pregnant women with CD4-cell counts >500 cells/mm3 should be started on a combination ARV regimen during pregnancy to prevent perinatal transmission. They should be assessed for their willingness and ability to commit to ongoing continuous therapy and counseled about the current treatment guidelines, the benefits and risks of therapy, the inconclusive nature of data on the clinical benefit of starting lifelong treatment at CD4-cell counts >500 cells/mm3, and the importance of adherence if the regimen is continued postpartum.
In general, when drugs are discontinued postnatally, all drugs should be stopped simultaneously. However, as discussed later (see "Stopping Antiretroviral Therapy during Pregnancy," below), in women receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens, continuing the dual-NRTI backbone for a period of time after stopping the NNRTI is recommended to reduce the development of NNRTI resistance. An alternative strategy is to replace the NNRTI with a protease inhibitor (PI) while continuing the NRTI, then to discontinue all the drugs at the same time. The optimal interval between stopping an NNRTI and stopping the other ARV drugs is unknown, but a minimum of 7 days is recommended. Drug concentrations may be detectable for more than 3 weeks after efavirenz is stopped in patients receiving an efavirenz-based NNRTI regimen. Therefore, for patients receiving efavirenz, some experts recommend continuing the other ARV agents or substituting a PI plus two other agents for up to 30 days.
Medical care of HIV-infected pregnant women requires coordination and communication between HIV specialists and obstetrical providers. General counseling should include current knowledge about risk factors for perinatal transmission. Risk of perinatal transmission of HIV has been associated with potentially modifiable factors including cigarette smoking, illicit drug use, genital tract infections, and unprotected sexual intercourse with multiple partners during pregnancy. Besides improving maternal health, cessation of cigarette smoking and drug use, treatment of genital tract infections, and use of condoms with sexual intercourse during pregnancy may reduce risk of perinatal transmission. In addition, the CDC recommends that HIV-infected women in the United States (including those receiving ART) refrain from breastfeeding to avoid postnatal transmission of HIV to their infants through breast milk and avoid premastication of food for their infants, a potential risk factor for transmission.
The National Perinatal HIV Hotline (1-888-448-8765)
The National Perinatal HIV Hotline is a federally funded service providing free clinical consultation to providers caring for HIV-infected women and their infants.
Recommendations for Use of Antiretroviral Drugs during Pregnancy
The Panel recommends that choice of ARV drug regimens for HIV-infected pregnant women be based on the same principles used to choose regimens for nonpregnant individuals, unless there are compelling pregnancy-specific maternal or fetal safety issues associated with specific drug choices. The Panel reviews clinical trial data published in peer-reviewed journals and data prepared by manufacturers for Food and Drug Administration (FDA) review related to treatment of HIV-infected adult women, both pregnant and nonpregnant. The durability, tolerability, and simplicity of a medication regimen is particularly important for preserving future options for women who will be stopping medications after delivery and women who meet standard criteria for initiation of ART per adult guidelines and will continue the regimen after pregnancy. Regimen selection should be individualized and the following factors should be considered:
- Patient adherence potential
- Potential adverse maternal drug effects
- Potential drug interactions with other medications
- Results of genotypic resistance testing
- Pharmacokinetic (PK) changes in pregnancy
- Potential teratogenic effects and other adverse effects on the fetuses or newborns
- Experience with use in pregnancy
Information used by the Panel for recommending specific drugs or regimens for pregnant women include:
- Data from randomized prospective clinical trials that demonstrate durable viral suppression as well as immunologic and clinical improvement
- Incidence rates and descriptions of short- and long-term drug toxicity of ARV regimens, with special attention to maternal toxicity and potential teratogenicity and fetal safety
- Specific knowledge about drug tolerability and simplified dosing regimens
- Known efficacy of some drug regimens in reducing mother-to-child transmission of HIV
- PK data during the prenatal period. (The physiologic changes of pregnancy have the potential to alter drug PKs. ARV dosing during pregnancy should be based on PK data from studies in pregnant women. Physiologic changes are not fixed throughout pregnancy but, rather, reflect a continuum of change as pregnancy progresses, with return to baseline at various rates in the postpartum period.)
- Data from animal teratogenicity studies
Categories of ARV regimens include:
- Preferred: Drugs or drug combinations are designated as preferred for use in pregnant women when clinical trial data in adults have demonstrated optimal efficacy and durability with acceptable toxicity and ease of use; pregnancy-specific PK data are available to guide dosing; and no evidence of teratogenic effects or established association with teratogenic or clinically significant adverse outcomes for mothers, fetuses, or newborns are present.
- Alternative: Drugs or drug combinations are designated as alternatives for initial therapy in pregnant women when clinical trial data in adults show efficacy but any one or more of the following conditions apply: experience in pregnancy is limited; data are lacking on teratogenic effects on the fetus; or the drug or regimen is associated with dosing, formulation, administration, or interaction issues.
- Use in Special Circumstances: Drugs and drug combinations in this category can be considered for use when intolerance or resistance prohibits use of other drugs with fewer toxicity concerns or in women who have comorbidities or require concomitant medications that may limit drug choice, such as active tuberculosis requiring rifampin therapy.
- Not Recommended: Drugs and drug combinations listed in this category are not recommended for therapy in pregnant women because of inferior virologic response, potentially serious maternal or fetal safety concerns, or pharmacologic antagonism.
- Insufficient Data to Recommend: The drugs and drug combinations in this category are approved for use in adults but lack pregnancy-specific PK or safety data, or such data are too limited to make a recommendation for use for pregnancy.
In pregnancy, a combination ARV regimen with at least three agents is recommended for either treatment or prophylaxis. Recommendations for choice of ARV drug regimen during pregnancy must be individualized according to a pregnant woman's specific ARV history and the presence of comorbidities. Some women may become pregnant and present for obstetrical care while receiving ART for their own health. In these cases, the choice of active drugs with known safety data in pregnancy may be more limited. In general, women who are already on a fully suppressive regimen should continue their regimens (see "HIV-Infected Pregnant Women Who Are Currently Receiving Antiretroviral Therapy," below).
Other HIV-infected women may not be receiving ART at the time they present for obstetrical care. Some women have never received ARV drugs, and others may have taken ARV drugs for treatment that was stopped, for prophylaxis to prevent perinatal transmission of HIV in prior pregnancies, or for pre- or post-exposure prophylaxis. The following sections provide detailed discussions of recommendations based on maternal ARV history and whether there are maternal indications for therapy.
For ARV-naive women, a combination regimen including two NRTIs and either an NNRTI or a PI (generally with low-dose ritonavir) would be preferred.
The preferred NRTI combination for ARV-naive pregnant women is zidovudine/lamivudine, based on efficacy studies in preventing perinatal transmission (see "Lessons from Clinical Trials of Antiretroviral Interventions to Reduce Perinatal HIV Transmission," above) and extensive experience with safe use in pregnancy. Alternate regimens can be used in women who are intolerant of zidovudine because of toxicity such as severe anemia or who have known resistance to the drug.
Tenofovir is a preferred NRTI for nonpregnant women. Data from the Antiretroviral Pregnancy Registry on 1,219 pregnancies with first-trimester exposure to the drug have shown no increase in overall birth defects compared with the general population. Animal studies, however, have shown decreased fetal growth and reduction in fetal bone porosity, and some studies in infected children on chronic tenofovir-based therapy have shown bone demineralization in some children. Therefore, tenofovir would be considered an alternative NRTI during pregnancy for ARV-naive women. For pregnant women with chronic HBV infection, however, tenofovir in combination with emtricitabine or lamivudine would be the preferred NRTI backbone of a combination ARV regimen. The combination of stavudine/didanosine should not be used in pregnant women because fatal cases of lactic acidosis and hepatic failure have been reported in women who received this combination throughout pregnancy.
In addition to the two NRTIs, either an NNRTI or a PI would be preferred for combination regimens in ARV-naive pregnant women. Efavirenz, the preferred NNRTI for nonpregnant adults, is not recommended for initiation in ARV-naive women in the first trimester because of concerns related to teratogenicity (see "Teratogenicity," below). Nonpregnant women of childbearing potential should undergo pregnancy testing before initiation of efavirenz and counseling about the potential risk to the fetus and desirability of avoiding pregnancy while on efavirenz-containing regimens. Alternate ARV regimens that do not include efavirenz should be strongly considered in women who 1) are planning to become pregnant or 2) are sexually active and not using effective contraception, assuming these alternative regimens are acceptable to the provider and are not thought to compromise the health of the woman. Because the risk of neural tube defects is restricted to the first 5–6 weeks of pregnancy and pregnancy is rarely recognized before 4–6 weeks of pregnancy, and unnecessary ARV drug changes during pregnancy may be associated with loss of viral control and increased risk of perinatal transmission, efavirenz may be continued in pregnant women receiving an efavirenz-based regimen who present for antenatal care in the first trimester, provided there is virologic suppression on the regimen (see "HIV-Infected Pregnant Women Who are Currently Receiving Antiretroviral Treatment," below). Initiation of efavirenz can be considered after the first trimester, based on clinical indication, but current data are limited in defining the safety of this use. Nevirapine would be the preferred NNRTI for ARV-naive pregnant women with CD4-cell counts <250 cells/mm3, and it can be continued in ARV-experienced women already receiving a nevirapine-based regimen, regardless of CD4-cell count. In general, nevirapine should not be initiated in treatment-naive women with CD4-cell counts >250 cells/mm3 because of an increased risk of symptomatic and potentially fatal rash and hepatic toxicity (see "Special Considerations Regarding the Use of Antiretroviral Drugs by HIV-Infected Pregnant Women and Their Infants," below). Elevated transaminase levels at baseline also may increase the risk of nevirapine toxicity. Safety and PK data on etravirine and rilpivirine in pregnancy are insufficient to recommend use of these NNRTI drugs in ARV-naive women.
Lopinavir/ritonavir and atazanavir with low-dose ritonavir boosting are the preferred PI drugs for use in ARV-naive pregnant women, based on efficacy studies in adults and experience with use in pregnancy (see Table 5 in the original guideline document for dosing considerations). Alternative PIs include ritonavir-boosted saquinavir or darunavir, although experience is more limited with these regimens in pregnancy. Nelfinavir can be considered in special circumstances when used solely for prophylaxis of perinatal transmission in ARV-naive women for whom therapy would not otherwise be indicated and who cannot tolerate alternative agents. PK data and extensive clinical experience do exist for nelfinavir in pregnancy, but the rate of viral response to nelfinavir-based regimens was lower than lopinavir/ritonavir or efavirenz-based regimens in clinical trials of initial therapy in nonpregnant adults. Indinavir also can be considered in special circumstances for women in whom preferred or alternative drugs cannot be used. Indinavir may be associated with renal stones and has a higher pill burden than many other PI drugs. Data on use in pregnancy are too limited to recommend routine use of fosamprenavir and tipranavir in pregnant women, although they can be considered for women who are intolerant of other agents.
Safety and PK data in pregnancy are insufficient to recommend use of the entry inhibitors enfuvirtide and maraviroc in ARV-naïve women during pregnancy. Use of these agents can be considered for women who have failed therapy with several other classes of ARV drugs after consultation with HIV and obstetric specialists.
Data on the integrase inhibitor raltegravir during pregnancy are limited but increasing; ART regimens including raltegravir can be considered for use in pregnancy in special circumstances when preferred and alternative agents cannot be used.
Although data are insufficient to support or refute the teratogenic risk of ARV drugs when administered during the first trimester, information to date does not support major teratogenic effects for the majority of such agents (for further data, see http://www.APRegistry.com ). However, certain drugs are of more concern than others—for example, efavirenz should be avoided during the first trimester of pregnancy (see "Supplement: Safety and Toxicity of Individual Antiretroviral Drugs in Pregnancy," in the original guideline document).
Table 5 in the original guideline document provides recommendations for use of specific ARV drugs in pregnancy and data on PK and toxicity in pregnancy. Table 6 in the original guideline document summarizes management recommendations for the mothers and infants in a variety of clinical scenarios.
HIV-Infected Pregnant Women Who Have Never Received Antiretroviral Drugs (Antiretroviral-Naive)
- All HIV-infected pregnant women should receive a potent combination ARV regimen to reduce the risk of perinatal transmission of HIV (AI). The choice of regimen should take into account current adult treatment guidelines, what is known about use of specific drugs in pregnancy, and the risk of teratogenicity (see Table 5 in the original guideline document).
- The decision as to whether to start the regimen in the first trimester or delay until 12 weeks' gestation will depend on T-lymphocyte (CD4-cell) count, HIV RNA levels, and maternal conditions such as nausea and vomiting (AIII). Earlier initiation of a combination ARV regimen may be more effective in reducing transmission, but benefits must be weighed against potential fetal effects of first-trimester drug exposure.
- Combination ARV regimens should include a dual NRTI backbone that includes one or more NRTIs with high levels of transplacental passage (zidovudine, lamivudine, emtricitabine, tenofovir, or abacavir) (AIII).
- ARV drug-resistance studies should be performed before starting the ARV drug regimen if HIV RNA is above the threshold for resistance testing (that is, >500–1,000 copies/mL) (see "Antiretroviral Drug Resistance and Resistance Testing in Pregnancy," below) (AI). If HIV is diagnosed later in pregnancy, the ARV regimen should be initiated promptly without waiting for the results of resistance testing (BIII).
- Nevirapine can be used as a component of the ARV drug regimen for pregnant women with CD4-cell counts ≤250 cells/mm3. In pregnant women with CD4-cell counts >250 cells/mm3, however, nevirapine should be used only if the benefit clearly outweighs the risk because the drug is associated with an increased risk of hepatic toxicity (AII).
Pregnant women with HIV infection should receive standard clinical, immunologic, and virologic evaluation.
They should be counseled about and offered combination ARV regimens containing at least 3 drugs for prevention of perinatal transmission of HIV. Use of an ARV regimen that successfully reduces plasma HIV RNA to undetectable levels substantially lowers the risk of perinatal transmission of HIV, lessens the need for consideration of elective cesarean delivery as an intervention to reduce risk of transmission, and reduces risk of ARV drug resistance in the mother. In an analysis of perinatal transmission in 5,151 HIV-infected women between 2000 and 2006 in the United Kingdom and Ireland, the overall mother-to-child transmission rate was 1.2%. A transmission rate of 0.8% was seen in women on ARV drugs for at least the last 14 days of pregnancy, regardless of the type of ARV regimen or mode of delivery. After adjustment for viral load, mode of delivery, and sex of the infant, longer duration of use of ARV drugs was associated with reduced transmission rates.
The ARV regimen used in pregnancy generally should consist of two NRTIs plus an NNRTI or PI, consistent with the principles of treatment for non-pregnant adults but taking into account what is known about use of the drugs in pregnancy and risks of teratogenicity (see "General Principles Regarding Use of Antiretroviral Drugs during Pregnancy," above). The regimen initiated during pregnancy can be modified after delivery to include simplified regimens that were not used in pregnancy because there were insufficient pregnancy safety data or drugs may be stopped in women who do not feel prepared to continue lifelong therapy at that point. Decisions regarding ARV use after pregnancy should be made by women in consultation with their HIV care providers, taking into account current recommendations and life circumstances (see "General Principles Regarding Use of Antiretroviral Drugs during Pregnancy," above).
Fetuses are most susceptible to the potential teratogenic effects of drugs during the first trimester and the risks of ARV drug exposure during that period are not fully known. Therefore, women in the first trimester who do not require immediate initiation of therapy for symptomatic HIV disease can consider delaying initiation of ARV drugs until after 12 weeks' gestation. This decision should be carefully considered by health care providers and the women. The discussion should include an assessment of a woman's health status and the benefits and risks to her health of delaying initiation of ARV drugs for several weeks.
Although most perinatal transmission of HIV events occur late in pregnancy or during delivery, recent analyses suggest that early control of viral replication may be important in preventing transmission. In a recent French study, lack of early and sustained control of maternal viral load appeared strongly associated with residual perinatal transmission of HIV. That study evaluated risk factors for perinatal transmission in women with HIV RNA <500 copies/mL at the time of delivery; overall HIV transmission was 0.5%. Women who transmitted were less likely to have received ARV drugs at the time of conception than were nontransmitters and were less likely to have HIV RNA <500 copies/mL at 14, 28, and 32 weeks' gestation. By multivariate analysis, plasma viral load at 30 weeks' gestation was significantly associated with transmission. Among women starting ARV drugs during pregnancy, the gestational age at initiation of therapy did not differ between groups (30 weeks), but viral load decreased earlier in the nontransmitters. The number of patients initiating therapy during pregnancy was too small to assess whether initiation of ARV drugs in the first trimester was associated with lower rates of transmission; although not statistically significant, viral load in naive women appeared to also decrease earlier in the nontransmitters. These data suggest that early and sustained control of HIV viral replication is associated with decreasing residual risk of transmission and favor initiating ARV drugs sufficiently early in naive women to suppress viral replication by the third trimester; however, this potential benefit must be balanced against the unknown long-term outcome of first-trimester drug exposure.
ARV drug-resistance testing should be performed before starting an ARV regimen if HIV RNA is above the threshold for resistance testing (that is, >500–1,000 copies/mL). For details regarding genotypic and phenotypic resistance testing, see the NGC summary of the CDC/DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Given the association of earlier viral suppression with lower risk of transmission as discussed above, if HIV is diagnosed in the second half of pregnancy the ARV regimen should be initiated promptly without waiting for the results of resistance testing. Because clinically significant resistance to PIs is less common than resistance to NNRTIs in ARV-naive individuals, a PI-based ARV drug regimen generally should be considered in this situation.
ARV prophylaxis is recommended for all pregnant women with HIV infection, regardless of viral load. Although rates of perinatal transmission are low in women with undetectable or low HIV RNA levels, there is no threshold below which lack of transmission can be ensured. The mechanism by which ARV drugs reduce perinatal transmission of HIV is multifactorial. Although lowering maternal antenatal viral load is an important component of prevention in women with higher viral load, ARV prophylaxis is effective even in women with low viral load. Additional mechanisms of protection include PrEP and post-exposure prophylaxis of the infant. With PrEP, passage of the ARV drug across the placenta results in presence of drug levels sufficient for inhibition of viral replication in the fetus, particularly during the birth process when there is intensive viral exposure. Therefore, whenever possible, combination ARV drug regimens initiated during pregnancy should include zidovudine or another NRTI with high transplacental passage, such as lamivudine, emtricitabine, tenofovir, or abacavir (see Table 5 in the original guideline document). With post-exposure prophylaxis, ARV drugs are administered to the infant after birth.
Use of nevirapine in pregnancy requires special consideration. A review of a large database of nevirapine studies indicated that women with CD4-cell counts >250 cells/mm3 have an increased risk of developing symptomatic, often rash-associated, nevirapine-related hepatotoxicity that can be severe, life threatening, and in some cases fatal. A more recent study involving 820 women in Kenya, Zambia, and Thailand, however, did not find an association between CD4-cell count and development of hepatotoxicity. Increased risk of rash and liver toxicity were associated with elevated baseline liver transaminases but not with CD4-cell count; all deaths from hepatic toxicity occurred in women with CD4-cell counts <100 cells/mm3 at baseline on concomitant anti-tuberculosis therapy. In women with CD4-cell counts >250 cells/mm3, nevirapine should be used as a component of a combination ARV regimen only when the benefit clearly outweighs the risk. If nevirapine is used, baseline and frequent monitoring of transaminase levels is required, particularly during the first 18 weeks of treatment (see "Nevirapine and Hepatic/Rash Toxicity" in the original guideline document). Transaminase levels should be checked before starting nevirapine and again in women who develop a rash. Nevirapine should be stopped immediately in women who develop signs or symptoms of hepatitis.
The use of raltegravir in late pregnancy for women who have high viral loads has been suggested because of its ability to rapidly suppress viral load (approximately 2-log copies/mL decrease by Week 2 of therapy). However, the efficacy and safety of this approach have not been evaluated and only anecdotal reports are available. Until more data become available on the safety of raltegravir use in pregnancy, this approach cannot be recommended for therapy-naive women.
Some women may wish to restrict fetal exposure to ARV drugs while reducing the risk of HIV transmission to their infants. Use of zidovudine alone during pregnancy for prophylaxis of perinatal transmission is not optimal, but it could be an option for women with low viral loads (that is, <1,000 copies/mL) on no ARV drugs. In the U.K. study discussed above, transmission rates were 0.7% for women receiving a triple-ARV drug regimen combined with planned cesarean delivery or with planned vaginal delivery and 0.5% in 464 women with HIV RNA levels below 10,000 copies/mL who received single-drug prophylaxis with zidovudine combined with planned cesarean delivery, not significantly different between groups. Zidovudine single-drug prophylaxis is recommended in the British HIV Association guidelines for women with HIV RNA levels <10,000 copies/mL and wild-type virus who do not require treatment for their own health. Time-limited administration of zidovudine during the second and third trimesters is less likely to induce development of resistance in women with low viral loads than in those with higher viral loads. This lower rate of resistance is likely because of the low level of viral replication and the short duration of exposure. Women's choices after counseling to use or not use ARV drugs during pregnancy should be respected.
After delivery, considerations regarding continuation of the ARV regimen for treatment of the mother are the same as for other nonpregnant adults (see "General Principles for Use of Antiretroviral Drugs during Pregnancy," above).
HIV-Infected Pregnant Women Who Are Currently Receiving Antiretroviral Treatment
- In general, pregnant women receiving and tolerating ART who present for care during the first trimester should continue treatment during pregnancy, assuming the regimen is tolerated and effective in suppressing viral replication (AII). The Panel recommends that efavirenz be continued in pregnant women receiving efavirenz-based ART who present for antenatal care in the first trimester provided the regimen is resulting in virologic suppression (see text in the original guideline document) (CIII).
- Pregnant women receiving and tolerating nevirapine-containing regimens who are virologically suppressed should continue the regimen, regardless of CD4 count (AIII).
- HIV ARV drug-resistance testing is recommended for pregnant women who have detectable viremia (that is, >500–1,000 copies/mL) on therapy (see "Failure of Viral Suppression" in the original guideline document) (AI).
HIV-Infected Pregnant Women Who Have Previously Received Antiretroviral Treatment or Prophylaxis But Are Not Currently Receiving Any Antiretroviral Medications
- Obtain an accurate history of all prior ARV regimens used for treatment of HIV disease or prevention of transmission, including virologic efficacy, tolerance to the medications, results of prior resistance testing, and any adherence issues (AIII).
- If HIV RNA is above the threshold for resistance testing (that is, >500–1,000 copies/mL), ARV drug-resistance studies should be performed before starting an ARV drug regimen (see "Antiretroviral Drug Resistance and Resistance Testing in Pregnancy," below) (AIII). In women who present late in pregnancy, therapy or prophylaxis should be initiated promptly without waiting for the results of resistance testing (BIII).
- Choose and initiate a combination ARV drug regimen based on results of resistance testing and prior history of ART while avoiding drugs with teratogenic potential or with known adverse potential for the mother (AII).
- Consult specialists in treatment of HIV infection about the choice of a combination ARV regimen in women who previously received ARV drugs for their own health (AIII).
- Perform repeat ARV drug-resistance testing (AI), assess adherence, and consult with an HIV treatment specialist to guide changes in ARV drugs in women do not achieve virologic suppression on their ARV regimens (see "Monitoring of the Woman and Fetus during Pregnancy," below).
Special Situations—HIV/Hepatitis B Virus Coinfection
- Screening for hepatitis B virus (HBV) infection with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs) is recommended for all pregnant women who have not been screened during the current pregnancy (AII).
- The HBV vaccine series should be administered to pregnant women who screen negative for hepatitis B (that is, HBsAg negative, anti-HBc negative, and anti-HBs negative) (AII).
- Pregnant women with chronic HBV infection should be screened for antibodies to hepatitis A virus (HAV), and those who screen negative should receive the HAV vaccine series (AII).
- Interferon-alfa and pegylated interferon-alfa are not recommended during pregnancy (AIII).
- The management of HIV/HBV coinfection in pregnancy is complex and consultation with an expert in HIV and HBV is strongly recommended (AIII).
- All pregnant women with HIV/HBV coinfection should receive ART, including a dual NRTI/nucleotide analogue reverse transcriptase inhibitor (NtRTI) backbone with two drugs active against both HIV and HBV (AII). Tenofovir plus lamivudine or emtricitabine is the preferred dual NRTI/NtRTI backbone of antepartum ART in HIV/HBV-coinfected pregnant women (AI).
- If ARV drugs are discontinued postpartum in women with HIV/HBV coinfection, frequent monitoring of liver function tests for potential exacerbation of HBV infection is recommended, with prompt reinitiation of treatment for both HIV and HBV if a flare is suspected (BIII).
- Pregnant women with HIV/HBV coinfection receiving ARV drugs should be counseled about signs and symptoms of liver toxicity, and liver transaminases should be assessed 1 month following initiation of ARV drugs and at least every 3 months thereafter (BIII).
- Within 12 hours of birth, infants born to women with HBV infection should receive hepatitis B immune globulin (HBIG) and the first dose of the HBV vaccine series. The second and third doses of vaccine should be administered at ages 1 and 6 months, respectively (AI).
Special Situations—HIV/Hepatitis C Virus Coinfection
- Screening for hepatitis C virus (HCV) infection is recommended for all HIV-infected pregnant women who have not been screened during the current pregnancy (AIII).
- Interferon alfa and pegylated interferon alfa are not recommended and ribavirin is contraindicated during pregnancy (AIII).
- Recommendations for ARV drug use during pregnancy are the same for women who have chronic HCV as for those without HCV coinfection (BIII).
- Pregnant women with HIV/HCV coinfection receiving ARV drugs should be counseled about signs and symptoms of liver toxicity, and transaminases should be assessed 1 month following initiation of ARV drugs and then every 3 months thereafter (BIII).
- Decisions concerning mode of delivery in HIV/HCV-coinfected pregnant women should be based on standard obstetric and HIV-related indications alone (see "Intrapartum Care," below) (BIII).
- Infants born to women with HIV/HCV coinfection should be evaluated for HCV infection with anti-HCV antibody testing after age 18 months (AII). Infants who test positive for anti-HCV antibodies should undergo confirmatory HCV RNA testing. If earlier diagnosis is indicated or desired, HCV RNA virologic testing can be performed between 3 and 6 months (AIII).
- Women who are found to have chronic HCV infection should be screened for HAV and HBV because they are at increased risk of complications from those two infections. Women with chronic HCV who are negative for hepatitis A immunoglobulin G (IgG) should receive the HAV vaccine series (AIII). If they are not infected with HBV (that is, hepatitis B surface antigen negative, hepatitis B core antibody negative, and hepatitis B surface antibody negative), they should receive the HBV vaccine series (AIII).
Special Situations—HIV-2 Infection and Pregnancy
- HIV-2 infection should be suspected in pregnant women who are from—or have partners from—countries in which the disease is endemic, who are HIV antibody positive on an initial enzyme-linked immunoassay screening test, and who have repeatedly indeterminate results on HIV-1 Western blot and an HIV-1 RNA viral load at or below the limit of detection (BII).
- A regimen with two NRTIs and a boosted PI currently is recommended for HIV-2-infected pregnant women who require treatment for their own health because they have significant clinical disease or CD4 counts <500 cells/mm3 (AIII).
- Based on available data on safety in pregnancy, zidovudine/lamivudine plus lopinavir/ritonavir would be preferred (AIII). Tenofovir plus lamivudine or emtricitabine plus lopinavir/ritonavir can be considered as an alternative (BIII).
- Optimal prophylactic regimens have not been defined for HIV-2-infected pregnant women who do not require treatment for their own health (that is, CD4-cell counts >500 cells/mm3 and no significant clinical disease). Experts have recommended the following approaches:
- A boosted PI-based regimen (two NRTIs plus lopinavir/ritonavir) for prophylaxis, with the drugs stopped postpartum (BIII); or
- Zidovudine prophylaxis alone during pregnancy and intrapartum (BIII)
- NNRTIs and enfuvirtide are not active against HIV-2 and should not be used for treatment or prophylaxis (AIII).
- All infants born to HIV-2-infected mothers should receive the standard 6-week zidovudine prophylactic regimen (BIII).
- In the United States, breastfeeding is not recommended for infants of HIV-2-infected mothers (AIII).
Special Situations—Acute HIV Infection
- When acute retroviral syndrome is suspected in pregnancy or during breastfeeding, a plasma HIV RNA test should be obtained in conjunction with an HIV antibody test (see "Identifying, Diagnosing, and Managing Acute HIV-1 Infection" in the NGC summary of the CDC/DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents) (AII).
- Repeat HIV antibody testing in the third trimester is recommended for pregnant women with initial negative HIV antibody tests who are known to be at risk of HIV, are receiving care in facilities that have an HIV incidence in pregnant women of at least 1 per 1,000 per year, are incarcerated, or reside in jurisdictions with elevated HIV incidence (see CDC's Revised Recommendations for HIV Testing of Adults, Adolescents, and Pregnant Women in Health-Care Settings ). (AII).
- All pregnant women with acute or recent HIV infection should start a combination ARV drug regimen as soon as possible to prevent mother-to-child transmission, with the goal of suppressing plasma HIV RNA to below detectable levels (AI).
- In women with acute HIV infection, baseline genotypic resistance testing should be performed simultaneously with initiation of the combination ARV regimen, and the ARV regimen should be adjusted, if necessary, to optimize virologic response (AIII).
- Because clinically significant resistance to PIs is less common than resistance to NNRTIs in ARV-naive individuals in general, a ritonavir-boosted PI-based regimen should be initiated (AIII).
Special Situations—Stopping Antiretroviral Therapy during Pregnancy
- HIV-infected women receiving ART who present for care during the first trimester should continue treatment during pregnancy (AII). If an ARV drug regimen is stopped acutely for severe or life-threatening toxicity, severe pregnancy-induced hyperemesis unresponsive to antiemetics, or other acute illnesses that preclude oral intake, all ARV drugs should be stopped and reinitiated at the same time (AIII).
- If an ARV drug regimen is stopped electively and the patient is receiving an NNRTI drug, consideration should be given to either: (1) stopping the NNRTI first and continuing the other ARV drugs for a period of time; or (2) switching from an NNRTI to a PI before interruption and continuing the PI with the other ARV drugs for a period of time before electively stopping. The optimal interval between stopping an NNRTI and the other ARV drugs is unknown; at least 7 days is recommended. Given the potential for prolonged detectable efavirenz concentrations for >3 weeks in patients receiving efavirenz-based therapy, some experts recommend continuing the other ARV agents or substituting a PI plus two other agents for up to 30 days (CIII).
- If nevirapine is stopped and more than 2 weeks have passed before restarting therapy, nevirapine should be restarted with the 2-week half-dose escalation period (AII).
Special Situations—Failure of Viral Suppression
- If an ultrasensitive HIV RNA assay indicates failure of viral suppression (that is, detectable virus) after an adequate period of treatment:
- Assess resistance and adherence (AII).
- Consult an HIV treatment expert (AIII).
- Scheduled cesarean delivery is recommended for HIV-infected pregnant women who have HIV RNA levels >1,000 copies/mL near the time of delivery (AII).
Monitoring of the Woman and Fetus during Pregnancy
- Plasma HIV RNA levels should be monitored at the initial visit (AI); 2 to 4 weeks after initiating (or changing) ARV drug regimens (BI); monthly until RNA levels are undetectable (BIII); and then at least every 3 months during pregnancy (BIII). HIV RNA levels also should be assessed at approximately 34 to 36 weeks' gestation to inform decisions about mode of delivery (see "Transmission and Mode of Delivery," below) (AIII).
- CD4-cell count should be monitored at the initial antenatal visit (AI) and at least every 3 months during pregnancy (BIII). Monitoring of CD4-cell count may be performed every 6 months in patients on ART for more than 2 to 3 years who are adherent to therapy, clinically stable, and have sustained viral suppression (BIII).
- Genotypic ARV drug-resistance testing should be performed at baseline in all HIV-infected pregnant women with HIV RNA levels >500–1,000 copies/mL, whether they are ARV-naive or currently on therapy (AIII). Repeat testing is indicated following initiation of an ARV regimen in women who have suboptimal viral suppression or who have persistent viral rebound to detectable levels after prior viral suppression on an ARV regimen (AII).
- Monitoring for complications of ARV drugs during pregnancy should be based on what is known about adverse effects of the drugs a woman is receiving (AIII).
- First-trimester ultrasound is recommended to confirm gestational age and, if scheduled cesarean delivery is necessary, to guide timing of the procedure (see "Transmission and Mode of Delivery," below) (AII).
- In women on effective ART, no perinatal transmissions have been reported after amniocentesis, but a small risk of transmission cannot be ruled out. If amniocentesis is indicated in HIV-infected women, it should be done only after initiation of an effective ART regimen and, if possible, when HIV RNA levels are undetectable (BIII). In women with detectable HIV RNA levels in whom amniocentesis is deemed necessary, consultation with an expert should be considered.
Special Considerations Regarding the Use of Antiretroviral Drugs by HIV-Infected Pregnant Women and Their Infants
Recommendations regarding the choice of ARV drugs for treatment of HIV-infected pregnant women are subject to unique considerations. These include:
- Possible changes in dosing requirements resulting from physiologic changes associated with pregnancy
- Potential toxicities of ARV drugs that may be exacerbated in pregnant women
- The PKs and toxicity of transplacentally transferred drugs
- The potential short- and long-term effects of the ARV drug on fetuses and newborns, including the potential for preterm birth, teratogenicity, mutagenicity, or carcinogenicity
ARV drug recommendations for HIV-infected pregnant women have been based on the concept that drugs of known benefit to women should not be withheld during pregnancy unless there are known adverse effects on the mother, fetus, or infant and unless these adverse effects outweigh the benefit to the woman. Pregnancy should not preclude the use of optimal drug regimens. The decision to use any ARV drug during pregnancy should be made by the woman after discussing with her health care provider the known and potential benefits and risks to her and her fetus.
- Altered dosing during pregnancy may be required for some PIs, such as lopinavir/ritonavir (see Table 5 in the original guideline document) (AII).
- All cases of ARV drug exposure during pregnancy should be reported to the Antiretroviral Pregnancy Registry (see details at http://www.APRegistry.com ) (AIII).
- Nonpregnant women of childbearing potential should undergo pregnancy testing before initiation of efavirenz and receive counseling about the potential risk to the fetus and desirability of avoiding pregnancy while on efavirenz-containing regimens (AIII).
- Alternate ARV regimens that do not include efavirenz should be strongly considered in women who are (1) planning to become pregnant or (2) sexually active and not using effective contraception, assuming these alternative regimens are acceptable to the provider and are not thought to compromise the woman's health (BIII).
- Because the risk of neural tube defects is restricted to the first 5 to 6 weeks of pregnancy and pregnancy is rarely recognized before 4 to 6 weeks of pregnancy, and unnecessary changes in ARV drugs during pregnancy may be associated with loss of viral control and increased risk of perinatal transmission, efavirenz can be continued in pregnant women receiving an efavirenz-based regimen who present for antenatal care in the first trimester, provided the regimen produces virologic suppression (see "HIV-Infected Pregnant Women Who are Currently Receiving Antiretroviral Treatment," above) (CIII).
Combination Antiretroviral Drug Regimens and Pregnancy Outcomes
- Clinicians should be aware of a possible small increased risk of preterm birth in pregnant women receiving PI-based combination ARV regimens; however, given the clear benefits of such regimens for both a women's health and prevention of mother-to-child transmission, PIs should not be withheld for fear of altering pregnancy outcome (AII).
Nevirapine and Hepatic/Rash Toxicity
- Nevirapine-based regimens should be initiated in women with CD4 T-lymphocyte (CD4-cell) counts >250 cells/mm3 only if the benefits clearly outweigh the risks because of the drug's potential for causing hepatic toxicity/hypersensitivity reaction (AII).
- Women who become pregnant while receiving nevirapine-containing regimens and who are tolerating the regimen well can continue on the therapy regardless of CD4 count (AII).
Nucleoside Reverse Transcriptase Inhibitor Drugs and Mitochondrial Toxicity
- The combination of stavudine and didanosine should not be prescribed during pregnancy due to reports of lactic acidosis and maternal/neonatal mortality with prolonged use in pregnancy (AII).
- Mitochondrial dysfunction should be considered in uninfected children with perinatal exposure to ARV drugs who present with severe clinical findings of unknown etiology, particularly neurologic findings (AII).
- Long-term clinical follow-up is recommended for any child with in utero exposure to ARV drugs (AIII).
Protease Inhibitor Therapy and Hyperglycemia
- HIV-infected women taking ARV drug regimens during pregnancy should undergo standard glucose screening at 24 to 28 weeks' gestation (AIII). Some experts would perform earlier glucose screening in women receiving ongoing PI-based regimens initiated before pregnancy, similar to recommendations for women with high-risk factors for glucose intolerance (BIII).
Antiretroviral Drug Resistance and Resistance Testing in Pregnancy
- HIV drug-resistance studies should be performed before starting or modifying ARV regimens in all pregnant women whose HIV RNA levels are above the threshold for resistance testing (that is, >500–1,000 copies/mL) before initiation of ARVs (AIII) and for those entering pregnancy with detectable HIV RNA levels while receiving ART or who have suboptimal viral suppression after starting ARVs during pregnancy (AII).
- In women who present late in pregnancy, an empiric ARV regimen should be initiated promptly without waiting for the results of resistance testing, with adjustment as needed after test results are available, for optimal prevention of perinatal transmission and maternal health (BIII).
- Women who have documented zidovudine resistance and are on regimens that do not include zidovudine for their own health should still receive intravenous zidovudine during labor along with their established ARV regimens if they have HIV RNA levels >400 copies/mL near delivery (see "Intrapartum Antiretroviral Prophylaxis/Therapy," below), unless a history of hypersensitivity is documented (AII).
- The optimal prophylactic regimen for newborns of women with ARV resistance is unknown (see "Infant Antiretroviral Prophylaxis," below). Therefore, ARV prophylaxis for an infant born to a woman with known or suspected drug resistance should be determined in consultation with a pediatric HIV specialist, preferably before delivery (see "Infant Antiretroviral Prophylaxis," below) (AIII).
- HIV-infected pregnant women should be given combination ARV drug regimens to maximally suppress viral replication, which is the most effective strategy for preventing development of resistance and minimizing risk of perinatal transmission (AII).
- All pregnant and postpartum women should be counseled about the importance of adherence to prescribed ARV medications to reduce the potential for development of resistance (AII).
- To minimize development of resistance, pregnant women who receive an NNRTI-based combination ARV regimen that is discontinued after delivery should receive either dual nucleoside analogue reverse transcriptase inhibitor agents alone (AI) or with a PI (BII) for 7 to 30 days (AII) after stopping the NNRTI drug. The optimal interval between stopping an NNRTI and the other ARV drugs is not known (see "Stopping Antiretroviral Therapy during Pregnancy," above, and "Postpartum Follow-Up of HIV-Infected Women," below).
Intrapartum Antiretroviral Therapy/Prophylaxis
- Women who are receiving an antepartum combination ARV drug regimen should continue this regimen on schedule as much as possible during labor and before scheduled cesarean delivery (AIII).
- Intravenous (IV) zidovudine should be administered to HIV-infected women with HIV RNA ≥400 copies/mL (or unknown HIV RNA) near delivery, regardless of antepartum regimen or mode of delivery (AI).
- IV zidovudine is not required for HIV-infected women receiving combination ARV regimens who have HIV RNA <400 copies/mL near delivery (BII).
- For women who have received antepartum ARV drugs but have suboptimal viral suppression near delivery (that is, HIV RNA >1,000 copies/mL), scheduled cesarean delivery is recommended (see "Mode of Delivery," below) (AI).
- Women whose HIV status is unknown 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 (IV zidovudine)/infant (combination ARV prophylaxis) 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 "Infant Antiretroviral Prophylaxis," below) (AI); if the test is negative, the infant ARV drugs should be stopped.
Transmission and Mode of Delivery
- Scheduled cesarean delivery at 38 weeks' gestation to minimize perinatal transmission of HIV is recommended for women with HIV RNA levels >1,000 copies/mL or unknown HIV levels near the time of delivery, irrespective of administration of antepartum ARV drugs (AII). Scheduled cesarean delivery is not recommended for prevention of perinatal transmission in pregnant women receiving combination ARV drugs with plasma HIV RNA levels <1,000 copies/mL near the time of delivery (BIII). Data are insufficient to evaluate the potential benefit of cesarean delivery used solely for prevention of perinatal transmission in women with HIV RNA levels <1,000 copies/mL, and given the low rate of transmission in these patients, it is unclear whether scheduled cesarean delivery would confer additional benefit in reducing transmission. In women with HIV RNA levels <1,000 copies/mL, cesarean delivery performed for standard obstetrical indications should be scheduled for 39 weeks' gestation.
- It is not clear whether cesarean delivery after rupture of membranes or onset of labor provides benefit in preventing perinatal transmission. Management of women originally scheduled for cesarean delivery who present with ruptured membranes or in labor must be individualized at the time of presentation based on duration of rupture and/or labor, plasma HIV RNA level, and current ARV regimen (BII).
- Women should be informed of the risks associated with cesarean delivery. If the indication for cesarean delivery is prevention of perinatal transmission of HIV, the risks to a woman should be balanced with potential benefits expected for the neonate (AIII).
Table 8 in the original guideline document summarizes recommendations regarding mode of delivery for different clinical scenarios.
Other Intrapartum Management Considerations
- The following should generally be avoided unless there are clear obstetric indications because of a potential increased risk of transmission:
- Artificial rupture of membranes (BIII)
- Routine use of fetal scalp electrodes for fetal monitoring (BIII)
- Operative delivery with forceps or a vacuum extractor and/or episiotomy (BIII)
- The ARV drug regimen a woman is receiving should be taken into consideration when treating excessive postpartum bleeding resulting from uterine atony:
- In women who are receiving a cytochrome P (CYP) 3A4 enzyme inhibitor such as a PI, methergine should only be used if no alternative treatments for postpartum hemorrhage are available and the need for pharmacologic treatment outweighs the risks. If methergine is used, it should be administered in the lowest effective dose for the shortest possible duration (BIII).
- In women who are receiving a CYP3A4 enzyme inducer such as nevirapine, efavirenz, or etravirine, additional uterotonic agents may be needed because of the potential for decreased methergine levels and inadequate treatment effect (BIII).
Postpartum Follow-up of HIV-Infected Women
- Contraceptive counseling should be included in the prenatal period as well as immediately postpartum as a critical aspect of postpartum care (AIII).
- Decisions about continuing ARV drugs after delivery should take into account current recommendations for initiation of ART, current and nadir CD4 T-lymphocyte counts and trajectory, HIV RNA levels, adherence issues, whether a woman has an HIV-uninfected sexual partner, and patient preference (AIII).
- For women continuing ARV drugs postpartum, arrangements for new or continued supportive services should be made before hospital discharge because the immediate postpartum period poses unique challenges to adherence (AII).
- Women with a positive rapid HIV antibody test during labor require immediate linkage to HIV care and comprehensive follow-up, including confirmation of HIV infection. If infection is confirmed, a full health assessment is warranted, including evaluation for associated medical conditions, counseling related to newly diagnosed HIV infection, and assessment of need for ART and opportunistic infection (OI) prophylaxis (AII).
- Breastfeeding is not recommended for HIV-infected women in the United States, including those receiving ART (AII).
The postpartum period provides an opportunity to review and optimize women's health care. Comprehensive care and support services are particularly important for women with HIV infection and their families, who often face multiple medical and social challenges. Components of comprehensive care include the following medical and supportive care services as needed:
- Primary, gynecologic/obstetric, and HIV specialty care for an HIV-infected woman
- Pediatric care for her infant
- Family planning services
- Mental health services
- Substance abuse treatment
- Support services
- Coordination of care through case management for a woman, her child(ren), and other family members
Support services should be tailored to individual women's needs and can include case management; child care; respite care; assistance with basic life needs, such as housing, food, and transportation; peer counseling; and legal and advocacy services. Ideally, this care should begin before pregnancy and should be continued throughout pregnancy and the postpartum period.
During the postpartum period, maternal medical services must be coordinated between obstetric care providers and HIV specialists. It is especially critical to ensure continuity of antepartum ARV drug regimen when such treatment is required for a woman's health. The decision about whether to continue ARV drugs after delivery should be discussed with a woman and made before delivery.
The postpartum period also is a critical time for addressing the issue of safer sex practices, secondary transmission prevention, and contraception. It is important that comprehensive family planning and preconception care be integrated into routine health visits. Women who receive family planning counseling during prenatal care are more likely to use effective contraception postpartum. Lack of breastfeeding is associated with earlier return of fertility; ovulation returns as early as 6 weeks postpartum, and even earlier in some women, putting them at risk of pregnancy shortly after delivery. Interpregnancy intervals of less than 18 months have been associated with increased risk of poor perinatal and maternal outcomes in HIV-uninfected women. Because of the stresses and demands of a new baby, women may be more receptive to use of effective contraception, yet simultaneously at higher risk of nonadherence to contraceptive use and, thus, unintended pregnancy. This is an important concern in women who are on an efavirenz-containing regimen because of the potential risk of teratogenicity in the first 5 to 6 weeks of pregnancy (the neural tube closes at 36–39 days after the last menstrual period). A "dual-protection" strategy, such as use of condoms plus a second highly effective contraceptive, is ideal for women with HIV infection because it provides simultaneous protection against unintended pregnancy, transmission of HIV, and acquisition or transmission of sexually transmitted disease. Longer term, reversible contraceptive methods, such as injectables, implants, and intrauterine devices (IUDs) should be included as options.
Drug interactions have been documented between oral contraceptives (OCs) and many ARV drugs (see Table 4 in the original guideline document); however, data primarily come from pharmacokinetic (PK) studies and the clinical implications have not been well studied. The magnitude of changes in contraceptive drug levels that may reduce contraceptive efficacy or increase contraceptive-associated adverse effects is unknown. Hormonal contraceptives can be used with ART in women who have no other contraindications. Additional or alternative methods of contraception can be recommended where drug interactions are known. Estrogen-containing hormonal contraceptives significantly lower levels of amprenavir/fosamprenavir and, therefore, coadministration is not recommended. Whether low-dose ritonavir boosting raises amprenavir levels sufficiently to allow coadministration is unknown. Depot medroxyprogesterone acetate (Depo-Provera, DMPA) PKs are not significantly affected by nevirapine, efavirenz, or nelfinavir, and levels of these drugs were not significantly altered by DMPA. Adverse effects of DMPA are no different in HIV-infected women on ARV drugs than in HIV-uninfected women. In one study, DMPA use was associated with an increase in acquisition of HIV by uninfected women and transmission of HIV from infected women to male partners, but other studies have not seen this association and further studies are needed. Other non-oral contraceptives, such as levonorgestrel implants, the combined contraceptive patch, the combined hormonal contraceptive vaginal ring, and the levonorgestrel IUD, are largely unstudied in combination with ARV drugs, but some data do exist on lopinavir/ritonavir interactions with the estrogen patch. ARV drug interactions may be of less concern with contraceptive methods that exert primarily local activity and have minimal systemic absorption, but there is still a potential for interaction if metabolic or elimination pathways are shared. The World Health Organization has summarized the research on hormonal contraception, IUD use, and risk of HIV infection. Permanent sterilization is appropriate only for women who are certain they do not desire future childbearing.
Decisions about whether to continue ARV drugs after delivery should be made in consultation with the HIV provider. Factors to be taken into consideration should include current recommendations for initiation of ART, current and nadir CD4-lymphocyte counts and trajectory, HIV RNA levels, adherence issues, partner HIV status, and patient preference. Women with nadir CD4 T-lymphocyte (CD4-cell) counts less than the currently recommended threshold for institution of ART and/or symptomatic HIV infection should be encouraged to continue their ARV regimens postpartum without interruption. The risks versus benefits of stopping combination ART drug regimens postpartum in women with high CD4-cell counts are being evaluated in the ongoing PROMISE study (clinical trial number NCT00955968). Unplanned changes in ARV regimens and discontinuations of ART in the postpartum period have led to viral load rebound.
Recent data from the HPTN 052 clinical trial showed that earlier initiation of ARV drugs led to a significant reduction in sexual transmission of HIV to uninfected partners in serodiscordant couples (see "Preconception Counseling and Care for HIV-Infected Women of Child-Bearing Age," above). HPTN 052 evaluated immediate versus delayed initiation of ART to HIV-infected individuals with CD4-cell counts between 350 and 550 cells/mm3. Based on the results from that trial, continued administration of ARV drugs may be recommended for prevention of sexual transmission of HIV for postpartum women who have CD4-cell counts between 350 and 550 cells/mm3 and have HIV-uninfected sexual partners, and it can be considered for those with CD4-cell counts greater than 550 cells/mm3 with HIV-uninfected sexual partners. It is important to counsel the woman that no single method (including treatment of the infected partner) is fully protective against HIV transmission and safer sexual practices should be continued.
Concerns have been raised about adherence to ARV regimens during the postpartum period, because a number of studies have found significant decreases in adherence postpartum. Women should be counseled that postpartum physical and psychological changes and the stresses and demands of caring for a new baby may make adherence more difficult and that additional support may be needed during this period. Health care providers should be vigilant for signs of depression and illicit drug or alcohol use that may require assessment and treatment and interfere with adherence. Poor adherence has been shown to be associated with virologic failure, development of resistance, and decreased long-term effectiveness of ART. Simplification of an ARV regimen (for example, to once-daily medications) can be considered. It may be preferable to temporarily interrupt ART in women who are unable to adhere to their regimens while they work with a provider on strategies to improve adherence. Efforts to maintain adequate adherence during the postpartum period may prolong the effectiveness of therapy (see the section on "Adherence" in the NGC summary of the CDC/DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents).
For women whose antepartum regimen included an NNRTI and who plan to stop ARV prophylaxis after delivery, consideration should be given to stopping the NNRTI and continuing the other ARV drugs for a period of time before stopping electively. The optimal interval between stopping an NNRTI and the other ARV drugs is unknown; a minimum of 7 days is recommended. Because efavirenz-based therapy has potential to result in prolonged, detectable NNRTI concentrations for more than 3 weeks, some experts recommend that patients receiving efavirenz continue their other ARV drugs or substitute a PI for the NNRTI drug in combination with their other ARV drugs for up to 30 days after stopping efavirenz (see "Stopping Antiretroviral Therapy during Pregnancy" and "Prevention of Antiretroviral Drug Resistance," above). Women whose antepartum regimen did not include an NNRTI and who plan to stop ARV prophylaxis after delivery should stop all ARV drugs at the same time. Doses of some PIs may be increased during pregnancy. For women continuing therapy, available data suggest that standard doses can be used again, beginning immediately after delivery.
Immediate linking to care, comprehensive medical assessment, counseling, and follow-up are required for women who test positive on rapid HIV antibody assay during labor or at delivery. To minimize the delay in definitive diagnosis, confirmatory HIV antibody testing should be performed as soon as possible after an initial positive rapid test. Women who test positive on rapid HIV antibody assay should not breastfeed unless a confirmatory HIV test is negative. Women with a new HIV diagnosis postpartum should receive the same thorough evaluation as other newly identified infected patients, including consideration of ART and prophylaxis for opportunistic infections, as indicated. Other children and partner(s) should be referred for HIV testing.
Infants Born to Mothers with Unknown HIV Infection Status
- For infants born to mothers with unknown HIV status, rapid HIV antibody testing of the mothers and/or infants is recommended as soon as possible after birth, with immediate initiation of infant ARV prophylaxis (see "Infant Antiretroviral Prophylaxis," below) if the rapid test is positive (AII).
- In the setting of a positive test, standard antibody confirmatory testing such as a Western blot also should be performed on mothers (or their infants) as soon as possible. Clinicians should not wait for the results of the confirmatory test before initiating postnatal prophylaxis. If the confirmatory test is negative, ARV prophylaxis can be discontinued (AIII).
- If the HIV antibody confirmatory test is positive, a newborn HIV DNA polymerase chain reaction (PCR) should be performed (AIII).
- If the newborn HIV DNA PCR is positive, ARV prophylaxis should be discontinued and the infant promptly referred to a pediatric HIV specialist for confirmation of the diagnosis and treatment of HIV infection with standard combination ART (AI).
Infant Antiretroviral Prophylaxis
- The 6-week neonatal component of the zidovudine chemoprophylaxis regimen is recommended for all HIV-exposed neonates to reduce perinatal transmission of HIV (AI).
- Zidovudine, at gestational age-appropriate doses, should be initiated as close to the time of birth as possible, preferably within 6–12 hours of delivery (AII).
- Infants born to HIV-infected women who have not received antepartum ARV drugs should receive prophylaxis with zidovudine given for 6 weeks combined with three doses of nevirapine in the first week of life (at birth, 48 hours later, and 96 hours after the second dose), begun as soon after birth as possible (AI).
- In other scenarios, the decision to combine other drugs with the 6-week zidovudine regimen should be made in consultation with a pediatric HIV specialist, preferably before delivery, and should be accompanied by counseling of the mother on the potential risks and benefits of this approach (BIII).
- In the United States, the use of ARV drugs other than zidovudine and nevirapine cannot be recommended in premature infants because of lack of dosing and safety data (BIII).
- The National Perinatal HIV Hotline (1-888-448-8765) provides free clinical consultation on all aspects of perinatal HIV, including infant care.
See the original guideline document for information on intrapartum maternal and neonatal dosing for zidovudine and other ARV drugs, as well as general considerations for choice of infant prophylaxis, including recommendations for specific clinical situations.
Initial Postnatal Management of the HIV-Exposed Neonate
- A complete blood count (CBC) and differential should be performed on newborns as a baseline evaluation (BIII).
- Decisions about the timing of subsequent monitoring of the hematologic parameters in infants will depend on baseline hematologic values, gestational age at birth, clinical condition of the infants, the zidovudine dose being administered, receipt of other ARV drugs and concomitant medications, and maternal antepartum ARV therapy (CIII).
- If hematologic abnormalities are identified in infants receiving prophylaxis, decisions on whether to continue infant ARV prophylaxis need to be individualized. Consultation with an expert in pediatric HIV infection is advised if early discontinuation of prophylaxis is considered (CIII).
- Some experts recommend more intensive monitoring of hematologic and serum chemistry and liver function assays at birth and when diagnostic HIV PCR tests are obtained in infants exposed to combination ARV drug regimens in utero or during the neonatal period (CIII).
- A recheck of hemoglobin and neutrophil counts is recommended 4 weeks after initiation of prophylaxis for infants who receive combination zidovudine/lamivudine-containing ARV prophylaxis regimens (AI).
- Routine measurement of serum lactate is not recommended. However, measurement can be considered if an infant develops severe clinical symptoms of unknown etiology (particularly neurologic symptoms) (CIII).
- Virologic tests are required to diagnose HIV infection in infants <18 months of age and should be performed within the first 14 to 21 days of life, at 1 to 2 months, and at 4 to 6 months of age (AII).
- To prevent Pneumocystis jirovecii pneumonia (PCP), all infants born to women with HIV infection should begin PCP prophylaxis at age 4 to 6 weeks, after completing their ARV prophylaxis regimen, unless there is adequate test information to presumptively exclude HIV infection (see the NGC summary of the CDC Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children) (AIII).
- Health care providers should routinely inquire about premastication of foods fed to infants, instruct HIV-infected caregivers to avoid this practice, and advise on safer feeding options (AII).
Long-Term Follow-up of Antiretroviral Drug-Exposed Infants
- Children with in utero/neonatal exposure to ARV drugs who develop significant organ system abnormalities of unknown etiology, particularly of the nervous system or heart, should be evaluated for potential mitochondrial dysfunction (CIII).
- Follow-up of children with exposure to ARVs should continue into adulthood because of the theoretical concerns regarding the potential for carcinogenicity of the nucleoside analogue ARV drugs (CIII).
Strength of Recommendation
- Strong recommendation for the statement
- Moderate recommendation for the statement
- Optional recommendation for the statement
Quality of Evidence for Recommendations
- One or more randomized trials with clinical outcomes and/or validated laboratory endpoints
- One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes
- Expert opinion