- MAJOR RECOMMENDATIONS
Note from the Centers for Disease Control and Prevention (CDC) and the National Guideline Clearinghouse (NGC): The current guidelines have been structured to better reflect the management of an individual mother-child pair, and are organized into principles for management of the woman and her infant during the antepartum, intrapartum, and postpartum period. Key issues and new information discussed in this report include:
- Lessons Learned from Clinical Trials of Antiretroviral Interventions to Reduce Perinatal Human Immunodeficiency Virus (HIV) Transmission and Table 1 in the original guideline document (Results of Major Studies on Antiretroviral Prophylaxis to Prevent Mother to Child HIV Transmission). There is a new brief discussion of recent trials on the use of antiretroviral drugs for prevention of mother-to-child HIV transmission through breastfeeding, with addition of these trials to Table 1 in the original guideline document. The Panel reaffirms that in the United States, where safe, affordable and feasible alternatives are available and culturally acceptable, breastfeeding is not recommended for HIV-infected women (including those receiving highly active combination antiretroviral therapy [HAART]).
- Neonatal Postnatal Care. A more detailed discussion of duration of infant zidovudine (ZDV) prophylaxis is provided. The Panel reaffirms the recommendation for administration of the standard 6 week course of infant prophylaxis unless there are concerns about adherence or toxicity; in such cases, consideration may be given to reducing the duration of infant prophylaxis from 6 to 4 weeks.
- Table 2 in the original guideline document (Preclinical and Clinical Data Relevant to the Use of Antiretrovirals in Pregnancy). Updated information regarding animal carcinogenicity and teratogenicity studies have been added as well as information on the new drug etravirine.
- Table 3 in the original guideline document (Antiretroviral Drug Use in Pregnant HIV-Infected Women: Pharmacokinetic and Toxicity Data in Human Pregnancy and Recommendations for Use in Pregnancy). Table 3 in the original guideline document has been revised to reflect new information on antiretroviral drug pharmacokinetics in pregnancy and add information and recommendations regarding the use of etravirine. Additionally, atazanavir is now listed as an “Alternative” drug for use in pregnancy, and tenofovir and efavirenz are now listed in the category of “Use in Special Circumstances”.
- Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy Supplement. Updated information on preclinical animal studies and the Antiretroviral Pregnancy Registry and new data from recent pharmacokinetic studies in pregnancy are provided.
Lessons from Clinical Trials of Antiretroviral Interventions to Reduce Perinatal HIV Transmission
Mechanisms of Action of Antiretroviral Prophylaxis in Reducing Perinatal HIV Transmission
- Antiretroviral drugs reduce perinatal transmission by several mechanisms, including lowering maternal antepartum viral load, and pre- and post-exposure prophylaxis of the infant. Therefore, for prevention of perinatal HIV transmission, combined antepartum, intrapartum, and infant antiretroviral prophylaxis is recommended.
International Clinical Trials of Short-Course Regimens for Prevention of HIV Perinatal Transmission
- Combination antepartum antiretroviral drug regimens are more effective than single-drug regimens in reducing perinatal transmission.
- Longer duration of antepartum antiretroviral prophylaxis (e.g., starting at 28 weeks gestation) is more effective than shorter duration (e.g., starting at 36 weeks gestation); therefore, for women who do not require immediate initiation of therapy for their own health, prophylaxis should be started by 28 weeks gestation (see “Recommendations for Use of Antiretroviral Drugs during Pregnancy,” below).
- If women do not receive antepartum antiretroviral drugs, intrapartum combined with infant antiretroviral prophylaxis should be given to reduce the risk of perinatal transmission (see “Intrapartum Care,” below), although this is not as effective as when antepartum therapy is also given.
- If women do not receive antepartum or intrapartum antiretroviral drugs, postnatal infant antiretroviral prophylaxis is recommended with a minimum of 6 weeks of zidovudine (ZDV) (see “Postpartum Care,” below).
- In the United States, the addition of single-dose intrapartum/newborn nevirapine (NVP) to the standard antepartum combination antiretroviral regimens used for prophylaxis or treatment in pregnant women is not recommended because it does not appear to provide additional efficacy in reducing transmission and may be associated with the development of NVP resistance.
- Breastfeeding is not recommended for HIV-infected women (including those receiving HAART) in the United States, where safe, affordable and feasible alternatives are available and culturally acceptable.
Perinatal HIV Transmission and Maternal HIV RNA Copy Number
- Use of antiretroviral drugs during pregnancy for prevention of perinatal transmission should be discussed with and provided to all infected pregnant women regardless of their HIV RNA level.
Preconceptional Counseling and Care for HIV-Infected Women of Childbearing Age
- Select effective and appropriate contraceptive methods to reduce the likelihood of unintended pregnancy. Contraceptive counseling is an essential component of care for HIV-infected women of reproductive age.
- Preconception counseling on safe sexual practices and eliminating alcohol, illicit drug use, and smoking are important both for maternal health as well as for fetal/infant health should the woman become pregnant.
- Choice of an antiretroviral regimen for treatment of HIV-infected women of childbearing potential needs to include consideration of effectiveness for treatment of maternal disease and the drug’s potential for teratogenicity should pregnancy occur.
- Attainment of a stable maximally suppressed viral load prior to conception is recommended for HIV-infected women who are on antiretroviral therapy and wish to become pregnant.
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 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 are unintended, it is important that preconception care be integrated into routine health visits. Therefore, HIV care providers who routinely care for women of reproductive age play an important role in promoting preconception health.
The fundamental principles of preconception counseling and care have been outlined by the CDC Preconception Care Work Group (see the NGC summary of the CDC guideline:
- Select effective and appropriate contraceptive methods to reduce the likelihood of unintended pregnancy. Providers should be aware of potential interactions of antiretroviral drugs with hormonal contraceptives that could lower contraceptive efficacy (See the
Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, Tables 21a and 21b).
- Counsel on safe sexual practices that prevent HIV transmission to sexual partners and protect women from acquiring sexually transmitted diseases (STDs) and the potential to acquire more virulent or resistant HIV strains.
- Counsel on eliminating alcohol, illicit drug use, and cigarette smoking.
- Educate and counsel women about risk factors for perinatal HIV transmission, strategies to reduce those risks, and potential effects of HIV or treatment on pregnancy course and outcomes.
- When prescribing antiretroviral treatment to women of childbearing potential, considerations should include the regimen’s effectiveness for treatment of HIV disease and the drugs’ potential for teratogenicity should pregnancy occur. Women who are planning to get pregnant should strongly consider use of antiretroviral regimens that do not contain efavirenz (EFV) or other drugs with teratogenic potential. In addition, the effectiveness of a regimen in preventing mother-to-child HIV transmission should be considered.
- Attain a stable, maximally suppressed maternal viral load prior to conception in women who are on antiretroviral therapy and want to get pregnant.
- Evaluate and control for therapy-associated side effects which may adversely impact maternal-fetal health outcomes (e.g., hyperglycemia, anemia, hepatic toxicity).
- Evaluate for appropriate prophylaxis for opportunistic infections and administration of medical immunizations (e.g., influenza, pneumococcal, or hepatitis B vaccines) as indicated.
- Encourage sexual partners to receive HIV testing and counseling and appropriate HIV care if infected.
- Counsel regarding available reproductive options, such as intrauterine or intravaginal insemination, that prevent HIV exposure to an uninfected partner; expert consultation is recommended.
- Breastfeeding by HIV-infected women is not recommended in the U.S. due to risk of HIV transmission.
Management of Pregnant Women with a Partner Known to Be HIV Infected
Increasingly clinicians may be faced with the situation in which an HIV-uninfected woman presents during pregnancy who relates that she has an HIV-infected partner. As is recommended for all pregnant women, the woman should be notified that HIV screening is recommended and that she will receive an HIV test as part of the routine panel of prenatal tests unless she declines. In addition, she should receive a second HIV test during the third trimester, preferably before 36 weeks of gestation, as is recommended for high-risk women. Furthermore, if the pregnant woman presents in labor with incomplete HIV testing (e.g., undocumented HIV test results or only one rather than two HIV tests), then she should be screened with a rapid HIV test on the labor and delivery unit. If the clinician suspects that a pregnant woman may be in the “window” period of seroconversion (i.e., has signs or symptoms consistent with acute HIV infection), then a plasma HIV RNA test can be used in conjunction with an HIV antibody test, and HIV testing may be repeated in 4 to 6 weeks. Women should be counseled regarding the symptoms of acute retroviral syndrome (i.e., fever, pharyngitis, rash, myalgia, arthralgia, diarrhea, headache) and the importance of seeking medical care and testing if she experiences such symptoms.
If results from either conventional or rapid HIV testing are positive, then the woman should receive interventions to reduce perinatal HIV transmission, including immediate initiation of appropriate antiretroviral 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 (e.g., rapid testing during labor) then it is appropriate to initiate interventions to reduce perinatal transmission even in the absence of confirmatory testing (see “Infant Antiretroviral Prophylaxis,” below). If HIV testing results are negative, then pregnant women with HIV-infected partners should be regularly counseled regarding the ongoing risk of HIV transmission. If the partner’s HIV status is at all uncertain, he should be encouraged to seek testing and appropriate care. All women and their partners should be counseled about the importance of correct and consistent condom use.
General Principles Regarding Use of Antiretroviral Drugs During Pregnancy
Medical care of the HIV-infected pregnant woman requires coordination and communication between HIV-specialists and obstetrical providers. General counseling should include current knowledge regarding risk factors for perinatal transmission. Cigarette smoking, illicit drug use, genital tract infections, and unprotected sexual intercourse with multiple partners during pregnancy have been associated with risk for perinatal HIV transmission; in addition to improving maternal health, discontinuing cigarette smoking and drug use, treatment of genital tract infections, and use of condoms with sexual intercourse during pregnancy may also reduce risk of perinatal transmission. In addition, the CDC recommends that HIV-infected women in the United States (including those receiving antiretroviral therapy) refrain from breastfeeding to avoid postnatal transmission of HIV to their infants through breast milk.
In addition to the standard antenatal assessments for all pregnant women, the initial evaluation of an HIV-infected pregnant woman should include an assessment of HIV disease status and recommendations regarding antiretroviral treatment or alteration of her current antiretroviral regimen. This initial assessment should include the following:
- Evaluation of the degree of existing immunodeficiency determined by past and current CD4 count
- Evaluation of the risk for disease progression and perinatal HIV transmission as determined by 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)
- Baseline evaluation with complete blood cell count, and renal and liver function testing
- History of prior and current antiretroviral therapy
- History of prior antiretroviral drug use for prevention of perinatal HIV transmission
- Results of prior and current HIV antiretroviral drug resistance studies
- Assessment of supportive care needs
Decisions regarding initiation of or alterations to antiretroviral therapy and the choice of antiretroviral regimens during pregnancy are complex. Factors influencing benefit and risk that are unique to pregnancy in addition to those common to all HIV-infected adults must be weighed. General guidelines for the use of antiretroviral drug treatment for the benefit of maternal health are the same as for women who are not pregnant. In addition, there are recommendations for the use of antiretroviral drugs for prophylaxis to prevent perinatal HIV transmission even in women for whom therapy would not otherwise be indicated.
In general, if plasma HIV RNA is detectable, antiretroviral drug resistance studies should be performed before starting antiretroviral therapy or prophylaxis. However, if HIV is diagnosed late in pregnancy, therapy should be initiated while awaiting results of resistance testing (see “Antiretroviral Drug Resistance and Resistance Testing in Pregnancy,” below).
Maternal toxicities and risks of therapy must be considered, along with the additional considerations of the potential impact of such therapy on the outcome of pregnancy and on the fetus and infant. These decisions are further complicated because there are only limited data on the long-term consequences for the woman on the use of antiretroviral drugs only during pregnancy for prophylaxis of transmission. Similarly, there are only limited data on the long-term consequences of in utero antiretroviral exposure for the infant.
Decisions regarding the use and choice of an antiretroviral regimen should be individualized based on the following factors:
- Gestational age of the pregnancy
- Antiretroviral treatment recommendations for the health of the HIV-infected woman
- The efficacy of antiretroviral regimens for prevention of perinatal HIV transmission
- Known, suspected, and in some cases unknown effects of particular drugs or regimens on the fetus and newborn, on the outcome of pregnancy, and for the woman
- HIV antiretroviral drug resistance studies
Discussion of treatment options with a pregnant woman should be noncoercive, and the final decision regarding use of antiretroviral drugs is the responsibility of the woman. The known benefits and known and unknown risks of such therapy during pregnancy should be considered and discussed. Results from preclinical and animal studies and available clinical information about use of the various antiretroviral agents during pregnancy should be discussed with the woman (see Table 2 and 3 in the original guideline document). Risks of these drugs during pregnancy should be placed in perspective by also discussing benefits of antiretroviral therapy for the health of the infected woman and for reducing the risk for HIV transmission to her infant.
Perinatal HIV transmission can occur even at low or undetectable HIV RNA copy numbers. Thus, HIV RNA levels should not be a determining factor when deciding whether to use antiretroviral drugs for prevention of perinatal transmission. Additionally, the efficacy of antiretroviral drugs is not solely related to lowering viral load. Therefore, antiretroviral prophylaxis should be recommended even to women who have a very low or undetectable viral load on no therapy.
Discussion with the woman about initiation of antiretroviral therapy should include the following:
- Maternal risk for disease progression and the benefits and risks of initiation of therapy for her own health
- Benefit of lowering HIV viral load to reduce the risk of perinatal transmission
- Benefit of antiretroviral prophylaxis independent of the effect on viral load as well as the additive benefit of combination antiretroviral regimens for preventing perinatal HIV transmission
- The possibility of development of drug resistance, including the need for strict adherence to the prescribed drug schedule to avoid its development, as well as the increased likelihood of development of resistance in the setting of high viral loads with use of nonsuppressive therapy
- The limited long-term outcome data for both infants with in utero antiretroviral exposure and for women who temporarily use antiretroviral drugs for prophylaxis of transmission
The importance of adherence to the antiretroviral treatment or prophylaxis regimen should be emphasized. Depending on individual circumstances, provision of support services, mental health services, and drug abuse treatment may be required. 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 adherence of the infected woman to antiretroviral treatment regimens. Long-range plans should be developed with the woman regarding continuity of medical care and decisions about antiretroviral therapy for her own health after the birth of her infant.
Recommendations for Use of Antiretroviral Drugs During Pregnancy
Recommendations for antiretroviral therapy during pregnancy must be individualized according to the specific antiretroviral history of the HIV-infected pregnant woman. Some women may be receiving antiretroviral therapy for their own health at the time they become pregnant, and present for obstetrical care on such therapy. Other HIV-infected women may not be receiving antiretroviral therapy at the time they present for obstetrical care. Some of these women will never have received antiretroviral drugs before, while other women may have previously received antiretroviral drugs, either for treatment that was stopped or for prophylaxis to prevent perinatal HIV transmission in prior pregnancies. Considerations for initiating therapy will differ for such women according to whether antiretroviral drugs are currently indicated for maternal health or solely for fetal protection. The antiretroviral recommendations below are divided into sections according to antiretroviral treatment status at the time the woman presents for care and whether there are indications for therapy.
Although data are insufficient to support or refute the teratogenic risk of antiretroviral drugs when administered during the first 10 weeks of gestation, information to date does not support major teratogenic effects of the majority of antiretroviral drugs. However, certain drugs are of more concern than others (see Table 2 and “Teratogenicity” in the original guideline document and the supplement “Safety and Toxicity of Individual Antiretroviral Drugs in Pregnancy” [see “Availability of Companion Documents” field]). For example, EFV should be avoided during the first trimester of pregnancy.
Three-drug combination regimens including nelfinavir have had extensive use in pregnancy. However, in September 2007, the U.S. manufacturer, Pfizer, sent a letter to providers regarding the presence of ethyl methane sulfonate (EMS), a process-related impurity, in Viracept (nelfinavir mesylate) available in the United States. Health care providers were advised not to initiate antiretroviral regimens containing Viracept (nelfinavir) in their pregnant female or new pediatric patients and to switch pregnant patients receiving Viracept (nelfinavir) to alternative therapy unless no alternative was available. As of March 31, 2008, all Viracept (nelfinavir) manufactured and released by Pfizer now meets the new final EMS limits established by the FDA for prescribing to all patient populations, including pregnant women and pediatric patients. Viracept (nelfinavir) may now be prescribed for pregnant women as an alternate protease inhibitor (PI) for women receiving antiretroviral therapy during pregnancy solely for prevention of maternal-to-child transmission.
Table 3 in the original guideline document provides recommendations about use of specific antiretroviral drugs in pregnancy as well as data on pharmacokinetics and toxicity in pregnancy. Table 4 in the original guideline document provides a summary of management recommendations for the mother and infant in a variety of clinical scenarios.
HIV-Infected Pregnant Women Who Are Currently Receiving Antiretroviral Treatment
*Dependent on the resistance assay being used; some assays require HIV RNA levels of >1,000 copies/mL for performance of the resistance assay, while other assays can be used with lower levels of viral replication.
While ZDV should be a component of the antenatal antiretroviral treatment regimen, there may be circumstances, such as the occurrence of severe ZDV-related toxicity or documented ZDV resistance, when this is not possible. Additionally, women receiving an antiretroviral regimen that does not contain ZDV but who have HIV RNA levels that are undetectable have a very low risk of perinatal transmission, and there may be concerns that substitution of ZDV for another component of the regimen or the addition of ZDV to the current regimen could compromise adherence to treatment. In such cases, continuing a non-ZDV-containing regimen that is fully suppressive is reasonable.
In general, women who have been receiving antiretroviral treatment for their HIV infection should continue treatment during pregnancy. Discontinuation of therapy could lead to an increase in viral load, which could result in a decline in immune status and disease progression as well as adverse consequences for both the fetus and the woman, including increased risk of HIV transmission. Therefore, HIV-infected women receiving antiretroviral therapy at the time of conception whose pregnancy is identified after the first trimester should always continue therapy.
HIV-infected women receiving antiretroviral treatment who present for care during the first trimester of pregnancy should be counseled regarding the benefits and potential risks of antiretroviral administration during this period, and continuation of therapy should be recommended. However, EFV should be avoided during the first trimester of pregnancy. If a woman is receiving EFV and her pregnancy is recognized during the first trimester, substitution of an alternative antiretroviral drug is recommended when possible (see “Monitoring of the Woman and Fetus during Pregnancy,” below).
Pregnant women who are receiving NVP-containing regimens with viral suppression and are tolerating the regimen well should continue therapy, regardless of CD4 count. While hepatic toxicity is a concern in women with a CD4 count >250 cells/mm3 at the time they first initiate an NVP-containing regimen, an increased risk of hepatic toxicity has not been seen in women who are receiving NVP-based therapy and have immune reconstitution with therapy.
HIV-Infected Pregnant Women Who Have Never Received Antiretroviral Drugs (Antiretroviral-Naïve)
Pregnant women with HIV infection should receive standard clinical, immunologic, and virologic evaluation. Decisions about the need for initiation of therapy should be based on standard guidelines in nonpregnant adults.
HIV-Infected Pregnant Women Not on Antiretroviral Therapy and Who Need Antiretroviral Treatment for Their Own Health
Any HIV-infected pregnant woman who meets standard criteria for initiation of antiretroviral therapy as per adult antiretroviral guidelines should receive potent combination antiretroviral therapy, generally consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor(s), with continuation of therapy postpartum. For women who require immediate initiation of therapy for their own health, treatment should be started as soon as possible, including in the first trimester, as the potential benefit of treatment for the mother outweighs potential fetal risks. The regimen should be chosen from those recommended for nonpregnant adults taking into account what is known about use of the drugs during pregnancy and risk of teratogenicity (see Table 3 and “Teratogenicity” in the original guideline document).
Women with CD4 counts >250 cells/mm3 have an increased risk of developing symptomatic, often rash-associated, NVP-related hepatotoxicity, which can be severe, life-threatening, and in some cases fatal. Therefore, NVP should only be used as a component of a combination regimen when antiretroviral therapy is being initiated in women with CD4 counts >250 cells/mm3 if the benefit clearly outweighs risk. If NVP is used, frequent and careful monitoring of transaminase levels, particularly during the first 18 weeks of treatment, is required (see “Nevirapine and Hepatic/Rash Toxicity” in the original guideline document). Transaminase levels should be checked in all women who develop a rash while receiving NVP. NVP should be stopped immediately in all women who develop signs or symptoms of hepatitis.
HIV-Infected Pregnant Women Not on Antiretroviral Therapy Who Require Antiretroviral Prophylaxis Solely to Prevent Perinatal HIV Transmission
HIV-infected pregnant women should be counseled regarding the benefits of antiretroviral therapy for prevention of perinatal transmission even when initiation of antiretroviral therapy is not recommended or considered optional on the basis of current guidelines for treatment of nonpregnant persons. Although such women are at low risk for clinical disease progression if antiretroviral treatment is delayed, use of an antiretroviral regimen that successfully reduces plasma HIV RNA to undetectable levels substantially lowers the risk of perinatal HIV transmission and lessens the need for consideration of elective cesarean delivery as an intervention to reduce transmission risk.
Because the fetus is most susceptible to the potential teratogenic effects of drugs during the first 10 weeks of gestation and the risks of antiretroviral therapy during that period are not fully known, women in the first trimester of pregnancy who do not require immediate initiation of therapy for their own health may consider delaying initiation until after 10 to 12 weeks gestation. This decision should be carefully considered by the health-care provider and the patient; a discussion should include an assessment of the woman’s health status, the benefits and risks to her of delaying initiation of therapy for several weeks, and the fact that most perinatal HIV transmission likely occurs late in pregnancy or during delivery.
Antiretroviral prophylaxis is recommended for all pregnant women with HIV infection, regardless of viral load. While rates of perinatal transmission are low in women with undetectable or low HIV RNA levels (e.g., <1,000 copies/mL), there is no threshold below which lack of transmission can be assured. The mechanism by which antiretroviral drugs reduce perinatal HIV transmission is multifactorial. While lowering maternal antenatal viral load is an important component of prevention in women with higher viral load, antiretroviral prophylaxis is effective even in women with low viral load and when maternal antenatal therapy is unable to be given. Additional mechanisms of protection include pre-exposure prophylaxis of the infant, provided by passage of the antiretroviral drug across the placenta so that inhibitory levels of drug are present in the fetus during the birth process, and post-exposure prophylaxis through continued administration to the infant. Although placental passage of ZDV is excellent, that of other antiretroviral drugs may be variable (see Table 2 in the original guideline document). Therefore, when combination antiretroviral therapy is initiated during pregnancy, ZDV should be included as a component of antenatal therapy whenever possible. If antenatal ZDV use is not possible, at least one agent with known transplacental passage should be part of the antiretroviral regimen (see Table 2 in the original guideline document).
Combination antiretroviral regimens containing at least three drugs (i.e., highly active antiretroviral therapy [HAART]) for prevention of perinatal HIV transmission should be discussed and offered to all pregnant women with HIV infection.
If HAART is given solely to reduce perinatal transmission, would not have been needed if the woman were not pregnant, and will be stopped postpartum, use of a three-drug regimen that is not considered to be one of the standard first-line regimens used for adults who require therapy may be considered. However, the regimen should be among those considered an alternative effective treatment for adults. In particular, the triple NRTI combination ZDV/lamivudine (3TC)/abacavir (ABC) regimen may be considered because of known pharmacokinetics profiles and published data suggesting acceptable toxicities during pregnancy. However, this regimen has inferior long-term virologic efficacy, and for women with high CD4 count but high viral load (i.e., CD4 count >350/mm3 and HIV RNA >100,000 copies/mL), use of first-line, more potent regimens should be considered. Dual NRTI therapy without the addition of a third drug (i.e., a protease inhibitor, NNRTI, or a third NRTI) is not recommended because of the potential for inadequate viral suppression and rapid development of resistance.
The time-limited use of ZDV monotherapy during pregnancy for chemoprophylaxis against perinatal transmission is controversial. However, some women may wish to restrict exposure of their fetus to antiretroviral drugs during pregnancy while still reducing the risk of transmitting HIV to their infants. Additionally, for women with low viral load, time-limited use of ZDV during the second and third trimesters of pregnancy is less likely to induce the development of resistance than in women with higher viral loads because of the low level of viral replication in the patient and the short duration of exposure to the antiretroviral drug. Thus, while controversial, the use of ZDV chemoprophylaxis alone during pregnancy might be an appropriate option for this subset of women (i.e., women with HIV RNA levels <1,000 on no treatment).
In general, if antiretroviral therapy is given solely for prevention of perinatal HIV transmission, the antiretroviral drugs are discontinued postnatally, with the option to reinitiate standard potent treatment regimens in the future according to usual criteria for nonpregnant individuals. Discussion regarding the decision to continue or stop treatment postpartum should occur before beginning therapy during pregnancy. Generally, 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 NNRTI-based regimens, continuing the dual NRTI backbone for a period of time (e.g., 7 days) after stopping the NNRTI should be considered to prevent the development of NNRTI resistance.
HIV-Infected Pregnant Women Who Have Previously Received Antiretroviral Treatment or Prophylaxis But Are Not Currently Receiving Any Antiretroviral Medications
Hepatitis B Virus Coinfection
Hepatitis C Virus Coinfection
Stopping Antiretroviral Therapy During Pregnancy
Failure of Viral Suppression
Monitoring of the Woman and Fetus During Pregnancy
Special Considerations Regarding the Use of Antiretroviral Drugs by HIV-Infected Pregnant Women and Their Infants
Recommendations regarding the choice of antiretroviral 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 antiretroviral drugs that may be magnified in the pregnant woman
- The potential short- and long-term effects of the antiretroviral drug on the fetus and newborn, including the potential for teratogenicity, mutagenicity, or carcinogenicity, which may not be known for certain antiretroviral drugs
- The pharmacokinetics and toxicity of transplacentally transferred drugs
Treatment recommendations for pregnant women infected with HIV have been based on the concept that therapies 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 therapeutic regimens. The decision to use any antiretroviral 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.
See the original guideline document for information on pharmacokinetic changes, teratogenicity, combination antiretroviral therapy and pregnancy outcome, nevirapine and hepatic/rash toxicity, protease inhibitor therapy and hyperglycemia, and mitochondrial toxicity and NRTI drugs.
Antiretroviral Drug Resistance and Resistance Testing in Pregnancy
Indications for Antiretroviral Drug Resistance Testing in HIV-Infected Pregnant Women
Incidence of Antiretroviral Resistance with Perinatal Prophylactic Regimens
Management of Antiretroviral Drug Resistance During Pregnancy
Prevention of Antiretroviral Drug Resistance
Intrapartum Antiretroviral Therapy/Prophylaxis
Table 5 in the original guideline document shows dosing for intravenous intrapartum ZDV given in continuous infusion during labor and neonatal ZDV dosing; Table 6 in the original guideline document shows intrapartum and neonatal dosing for additional drugs to be considered in certain situations as delineated below.
Transmission and Mode of Delivery
Table 7 in the original guideline document provides a summary of recommendations regarding mode of delivery for different clinical scenarios.
Maternal Risks of Morbidity by Mode of Delivery
Other Intrapartum Management Considerations
Postpartum Follow-up of HIV-Infected Women
Comprehensive care and support services are particularly important for women with HIV infection and their families, who often face multiple social and medical challenges. Components of comprehensive care include the following medical and supportive care services:
- Primary, gynecologic/obstetric, pediatric, and HIV specialty care
- Family planning services
- Mental health services
- Substance abuse treatment
- Support services
- Coordination of care through case management for the woman, her children, and other family members
Support services should be tailored to the individual woman’s needs and may include case management, child care, respite care, assistance with basic life needs (e.g., 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 postpartum.
Maternal medical services during the postpartum period must be coordinated between obstetric care providers and HIV specialists. Continuity of antiretroviral treatment when such treatment is required for the woman’s HIV infection is especially critical and must be ensured. The decision whether or not to continue antiretroviral therapy after delivery will depend on the woman’s nadir CD4 count, clinical symptoms/disease stage, presence of other indications for antiretroviral therapy, and patient and provider preference. Ideally, a discussion of these factors should occur well before delivery.
Concerns have been raised about adherence to antiretroviral regimens during the postpartum period. Women should be counseled about the fact that the physical and psychological changes of the postpartum period, as well as the stresses and demands of caring for a new baby, might make adherence more difficult and additional support may be needed to maintain good adherence to their therapeutic antiretroviral regimen during this period. The health care provider should be vigilant for signs of depression and illicit drug or alcohol use, which may require assessment and treatment and which may interfere with adherence. Poor adherence has been shown to be associated with virologic failure, development of resistance, and decreased long-term effectiveness of antiretroviral therapy. Efforts to maintain adequate adherence during the postpartum period might prolong the effectiveness of therapy. The “Adherence” section in the “Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents” is available at the AIDSinfo Web site (http://AIDSinfo.nih.gov).
Women with nadir CD4 counts <350 cells/mm3 and/or symptomatic HIV infection should be encouraged to continue antiretroviral therapy postpartum with no interruption. For women who began antiretroviral therapy with a nadir CD4 count >350 cells/mm3 for prophylaxis of transmission, the decision on whether to continue therapy after delivery should be made in consultation with her HIV provider, taking into account current and nadir CD4+ lymphocyte counts and trajectory, HIV RNA levels, and patient preference. For women who received an NNRTI drug as part of the antepartum regimen and who plan to stop antiretroviral therapy after delivery, consideration should be given to stopping the NNRTI and continuing the other antiretroviral drugs for a period of time (e.g., 7 days) to decrease the risk of NNRTI resistance (see “Stopping Antiretroviral Therapy during Pregnancy,” above).
Neonatal Postnatal Care
Infants Born to Mothers with Unknown HIV Infection Status
Infant Antiretroviral Prophylaxis
See the original guideline document for information on dosing for full-term and premature infants, as well as general considerations for choice of infant prophylaxis, including recommendations for specific clinical situations.
Initial Postnatal Management of the HIV-Exposed Neonate
Long-Term Follow-Up of Antiretroviral Drug-Exposed Infants
TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS
The type of evidence supporting the recommendations is not specifically stated.
Not applicable: The guideline was not adapted from another source.
1998 Jan 30 (revised 2009 Apr 29)
Centers for Disease Control and Prevention – Federal Government Agency [U.S.]
Department of Health and Human Services (U.S.) – Federal Government Agency [U.S.]
Public Health Service (U.S.) – Federal Government Agency [U.S.]
SOURCE(S) OF FUNDING
United States Government
Perinatal HIV Guidelines Panel
COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE
Consultants: Erika Aaron, MSN, ANP, RNP, Drexel University College of Medicine, Philadelphia, PA; Elaine Abrams, MD (Co-chair), Harlem Hospital, New York, NY; Jean Anderson, MD, Johns Hopkins University School of Medicine, Baltimore, MD; Dawn Averitt Bridge, The Well Project, Charlottesville, VA; Rana Chakraborty, MD, MSc, FRCPCH, DPhil, Emory University School of Medicine, Atlanta, GA (affiliation August 2008); Susan E. Cohn, MD, MPH, University of Rochester Medical Center, Rochester, NY; Amanda Cotter, MD, University of Miami Miller School of Medicine, Miami, FL; Susan Cu-Uvin, MD, The Miriam Hospital, Brown University, Providence, RI; Judith Feinberg, MD, University of Cincinnati College of Medicine, Cincinnati, OH; Patricia Flynn, MD, St. Jude’s Medical Center, Memphis, TN; Mary Glenn Fowler, MD, MPH, Johns Hopkins University School of Medicine, Baltimore, MD; Jane Hitti, MD, MPH, University of Washington, Seattle, WA; Robert Maupin, MD, Louisiana State University Health Sciences Center, New Orleans, LA; Howard Minkoff, MD, Maimonides Medical Center, Brooklyn, NY; Mark Mirochnick, MD, Boston Medical Center, Boston, MA; Fatima Y. Prioleau, MA, Brooklyn, NY; Stephen Spector, M.D., University of California San Diego, La Jolla, CA; Ruth Tuomala, MD (Co-chair), Brigham and Women’s Hospital, Boston, MA; Geoffrey A. Weinberg, MD, University of Rochester School of Medicine and Dentistry, Rochester, NY
Ex Officio: Jess Fogler, MD, Assistant Director, National Perinatal HIV Hotline, San Francisco, CA
Federal Government Staff: Magda Barini-Garcia, MD, Health Resources and Services Administration, Rockville, MD; Alan Shapiro, MD, PhD, Food and Drug Administration, Rockville, MD; Brian Feit, MPA, Health Resources and Services Administration, Rockville, MD; Denise Jamieson, MD, MPH, Centers for Disease Control and Prevention, Atlanta, GA; Edward Handelsman, MD, National Institutes of Health, Rockville, MD; Lynne Mofenson, MD (Executive Secretary), National Institutes of Health, Rockville, MD; D. Heather Watts, MD, National Institutes of Health, Rockville, MD
Perinatal Panel Coordinating Center Staff: Carolyn Burr, EdD, RN, Francois-Xavier Bagnoud Center, UMDNJ, Newark, NJ; Veronica Jones, MS, Francois-Xavier Bagnoud Center, UMDNJ, Newark, NJ; Andrea Norberg, MS, RN, National Resource Center at the Francois-Xavier Bagnoud Center, UMDNJ, Newark, NJ; Elaine Gross, RN, MS, CNS-C, Francois-Xavier Bagnound Center, UMDNJ, Newark, NJ; Linda Podhurst, PhD, National Resource Center at the Francois-Xavier Bagnound Center, UMDNJ, Newark, NJ
FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST
- Abbott Laboratories (Speaker with honoraria)
- Boehringer Ingelheim (Grant recipient)
- Abbott Laboratories (Advisory Board member)
- Pfizer Inc. (Advisory Board member, speakers bureau, research support, educational program support, stockholder)
- GlaxoSmithKline (Speaker with honoraria, educational program support)
- Abbott Laboratories (Speaker with honoraria, educational program support)
- Boehringer Ingelheim (Educational program support, Advisory Board member)
Dawn Averitt Bridge
- Merck & Co., Inc. (Vaccine Advisory Panel; stockholder)
- Quest Diagnostics (Stockholder)
- The Well Project, Inc. (Women’s Health Initiative member)
- HIVMA (Board of Directors)
- Bristol Myers Squibb (Advisory Board)
- Boehringer Ingelheim (Advisory Board; speaker)
- Evo Pharmaceutical (Advisory Board)
- Merck & Co., Inc. (Speakers bureau)
- GlaxoSmithKline (Honoraria)
- Boehringer Ingelheim (Advisory Board member; speakers bureau)
- Bristol Myers Squibb (Advisory Board member; speakers bureau; grant recipient)
- Abbott Laboratories (Speakers bureau; consultant)
- GlaxoSmithKline (Speakers bureau)
- Achillion (Grant recipient)
- Panacos (Grant recipient)
- Koronis (Advisory board; grant recipient)
- Pfizer Inc. (Speakers bureau; Advisory Board; grant recipient)
- Tibotec (Speakers bureau; Advisory Board; grant recipient)
- Roche (Grant recipient)
- Theratechnology (Grant recipient)
- Neurogesx (Grant recipient)
- Gilead (Speakers bureau; consultant)
- Merck & Co., Inc. (Speakers bureau; consultant)
- The Well Project, Inc. (Think tank member)
- American Academy of HIV Medicine (Board of Directors member)
- MedImmune, Inc. (Clinical research support)
- Merck & Co., Inc. (Clinical research support)
- Tibotec (Clinical research support)
Mary Glenn Fowler
- Boehringer Ingelheim (Advisory Board)
- Pfizer Inc. (Research support)
- GlaxoSmithKline (Clinical research support)
- Pfizer Inc. (Stockholder)
- Boehringer Ingelheim ([Ad hoc] Consultant)
- Pfizer Inc. (Data Safety Monitoring Board)
Top^Top^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. Since many women infected with HIV are aware of their HIV status prior to pregnancy, there may be opportunities to address issues that impact pregnancy prior to conception during routine medical care for their HIV disease. In addition to those outlined by the CDC Preconception Care Work Group, the following components of preconception counseling and care are recommended for HIV-infected women:
- Perinatal HIV Guidelines Working Group. Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. Rockville (MD): Public Health Service Task Force; 2009 Apr 29. 111 p. [388 references]
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