Clinical Guide > HIV Treatment > Pregnancy

Care of HIV-Infected Pregnant Women

January 2011

Background

This chapter describes the elements involved in caring for the pregnant woman with HIV infection, whether the woman was known to be HIV infected before conception or was found to be HIV infected during pregnancy. It is not intended to be a comprehensive discussion of this topic, and an HIV-experienced obstetrician and an HIV specialist should be involved in the management of all HIV-infected pregnant women. For centers that do not have HIV specialists available, experts at the National Perinatal HIV Consultation and Referral Service are available for consultation through the Perinatal HIV Hotline (888-448-8765).

The goals of HIV management during pregnancy are to maintain and support the woman's health, provide optimal antiretroviral treatment (ART) to preserve or restore her immune system and suppress viral replication, and to offer interventions that decrease the risk of perinatal HIV transmission. According to the U.S. Department of Health and Human Services perinatal guidelines, Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States, all HIV-infected pregnant women should be given ART during pregnancy to prevent mother-to-child transmission of HIV, regardless of whether ART is indicated for the woman's own health (see chapter Reducing Maternal-Infant HIV Transmission).

The first task in caring for an HIV-infected woman who is pregnant or considering pregnancy is to provide counseling that will allow her to make informed reproductive choices. Taking a careful reproductive history and providing preconception counseling should be part of any woman's routine primary care. To make informed choices about pregnancy, the patient needs education and information about the risk of perinatal transmission of HIV, potential complications of pregnancy, continuation or modification (or possibly, initiation) of ART, and the support she will need to optimize maternal and fetal outcomes. See chapter Health Care of HIV-Infected Women Through the Life Cyclefor a more detailed discussion of preconception evaluation.

If ART is indicated for the woman's own health, an appropriate regimen should be started before pregnancy, to attain a stable, maximally suppressed maternal viral load prior to conception. Antiretroviral (ARV) resistance testing should be performed before ART is initiated. Particular ARVs should be avoided, including those with increased risk of causing teratogenicity (e.g., efavirenz), hepatotoxicity (e.g., nevirapine), or metabolic complications such as lactic acidosis (e.g., didanosine and stavudine). See chapter Reducing Maternal-Infant HIV Transmission. It should be noted that most fetal organogenesis occurs in the early weeks of pregnancy, before most women know that they are pregnant. Thus, any medication with potential teratogenicity or fetal toxicity, whether an ARV or another drug, should not be administered to women who intend to become pregnant or may become pregnant. Certain medications (e.g., ribavirin) also should be avoided by male partners of women who may become pregnant.

Folate supplementation to reduce the risk of neural tube defects in the developing fetus should be started at least 1 month before conception, if possible, because the neural tube forms in the early weeks of pregnancy (see below).

Evaluation and Counseling of Pregnant Women

All HIV-infected pregnant women should receive thorough education and counseling about perinatal transmission risks, strategies to reduce those risks, and potential effects of HIV infection or HIV treatment on the course or outcomes of pregnancy.

• The goals of therapy for pregnant women receiving ART, as for all persons being treated for HIV infection, are to suppress the HIV viral load maximally (preferably to undetectable levels) for as long as possible, to improve quality of life, to restore or preserve immune function, and, for pregnant women specifically, to reduce the risk of perinatal transmission as much as possible.
• Therapy-associated adverse effects, including hyperglycemia, anemia, and hepatic toxicity, may have a negative effect on maternal and fetal health outcomes. Pregnant women should be advised about possible ARV-related adverse effects and should be monitored regularly for these events.
• HIV-infected women should receive evaluation and appropriate prophylaxis for opportunistic infections (OIs), as well as the vaccinations indicated for persons with HIV infection (see below).
• Some medications, both ARVs and other drugs, may cause fetal anomalies or toxicity when taken during pregnancy. These should be avoided in pregnant women, unless the anticipated benefit outweighs the risk. Consult with an HIV or obstetric specialist, a pharmacist, or the drug labeling information before prescribing medications for pregnant women.
• Options for mode of delivery should be discussed early. The benefits and risks of vaginal vs. cesarean delivery are outlined in the perinatal guidelines. If the HIV viral load is >1,000 copies/mL at 36 weeks of pregnancy, a scheduled cesarean delivery at 38 weeks' gestation is recommended to further reduce the risk of transmission.

Other evaluation and support measures for pregnant women should include the following:

• Screening for other potential maternal health problems, such as diabetes and hypertension
• Maternal nutritional evaluation and support, including initiation of a prenatal multivitamin containing folate (0.4-0.8 mg PO once daily) to reduce the risk of fetal neural tube defects; for women receiving trimethoprim-sulfamethoxazole, some experts recommend a folate dose of 4 mg daily
• Screening for psychiatric and neurologic disease
• Counseling about the risks of tobacco smoking; smoking cessation support as indicated (see chapter Smoking Cessation)
• Counseling about the risks of alcohol or drug use and support for discontinuation of these activities as neede
• Intimate partner violence screening
• Review of medications, including over-the-counter and nutritional agents, and discontinuation of medications with the potential for fetal harm
• Immunizations (e.g., influenza, hepatitis B) as indicated
• Institution of the standard measures for evaluation and management (e.g., assessment of reproductive and familial genetic history, screening for infectious diseases or sexually transmitted infections [STIs])
• Planning for maternal-fetal medicine consultation, if desired or indicated
• Selection of effective and appropriate postpartum contraceptive methods, if desired

Comprehensive Care of Pregnant Women with HIV Infection

Comprehensive care is important for pregnant women with HIV infection to achieve a healthy pregnancy and delivery. A multidisciplinary approach is the most effective way to address the medical, psychological, social, and practical challenges. For example, while her medical care is being managed by her obstetrician and an HIV specialist, the pregnant woman may need help from a social worker to find appropriate social services for food, housing, child care, and parenting issues. The pregnant woman may need counseling and psychological support for herself and her partner, as well as referrals for substance abuse and detoxification programs. Peer counselors may be of particular assistance. Some patients may need legal or domestic violence services during and after pregnancy. Cooperation and communication between the obstetrician or nurse/midwife and the primary HIV provider are imperative throughout the pregnancy and early postpartum period. Referral to a maternal-fetal medicine specialist may be needed in complicated obstetric cases.

Prenatal Care

All of the pregnancy-related complications seen in HIV-uninfected women, such as hypertensive disorders, ectopic pregnancy, psychiatric illness, multiple gestation, preterm delivery, and STIs, also can occur in HIV-infected women. These problems must be recognized quickly and treated appropriately to avoid life-threatening complications. Ideally, HIV-infected pregnant women are managed by both an experienced obstetrician-gynecologist and an HIV specialist. Communication between these specialists about medications, expectations, and complications is vital for the health and well-being of both mother and baby. If complications occur or abnormalities are detected, they should be evaluated and treated as indicated by the condition, and referral should be made to a maternal-fetal medicine specialist, if possible. Antenatal fetal surveillance and testing to identify fetal abnormalities should be carried out using guidelines established by the American College of Obstetricians and Gynecologists.

The suggested testing and monitoring practices for pregnant women with HIV infection, from the first trimester to labor and delivery, are presented in Tables 1 and 2.

Immunizations and Opportunistic Infection Prophylaxis

Immunizations During Pregnancy

Immunizations should be given before pregnancy, if possible. Immunizations should be considered during pregnancy when the risk of exposure to an infection is high, the risk of infection to the mother or fetus is high, and the vaccine is unlikely to cause harm. Some vaccinations (particularly live-virus vaccines such as measles/mumps/rubella) are contraindicated, and others should be given only if the anticipated benefit of the vaccination outweighs its risk. Special considerations for immunizations in HIV-infected individuals are discussed in chapter Immunizations for HIV-Infected Adults and Adolescents.

Some clinicians avoid giving immunizations during the third trimester of pregnancy because vaccinations may cause a transient increase in the HIV viral load and theoretically may increase the risk of perinatal HIV transmission. An increase in viral load may be prevented with effective ART, and some clinicians defer immunizations until ART is under way.

Recommendations related to immunizations during pregnancy are shown in Table 3.

Opportunistic Infection Prophylaxis

Some OIs can have an adverse effect on pregnancy. In turn, pregnancy can affect the natural history, presentation, treatment, and significance of some OIs. Women should be monitored carefully for OIs during pregnancy, with special attention given to nonspecific symptoms such as fatigue, back pain, and weight loss, which may be attributable to HIV-related illness rather than to pregnancy. Respiratory symptoms in particular merit rapid, aggressive investigation. Clinicians should follow the most current recommendations of the U.S. Centers for Disease Control and Prevention (CDC), National Institutes of Health, and Infectious Diseases Society of America, Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, which give special consideration to pregnant women for each OI discussed. The indications and recommendations for OI prophylaxis generally should follow the guidelines for adults (see chapter Opportunistic Infection Prophylaxis). However, because of the risks of teratogenicity or harm to the developing fetus, some drugs routinely used for prophylaxis of OIs in nonpregnant adults are contraindicated during the first trimester of pregnancy, whereas others should not be used at any time during pregnancy.

Special Considerations for OI Prophylaxis During Pregnancy

Trimethoprim-sulfamethoxazole

Trimethoprim inhibits the synthesis of metabolically active folic acid. In pregnant women, folate deficiency increases the risk of neural tube defects in the developing fetus. Pregnant women, or women who may become pregnant, who are taking trimethoprim-sulfamethoxazole (Septra, Bactrim, cotrimoxazole) have an increased risk of folate deficiency and should be given folate supplementation to reduce the risk of neural tube defects. Some experts recommend a folate dose of 4 mg daily for women receiving trimethoprim-sulfamethoxazole.

Genital herpes

Women with HIV infection are more likely than HIV-uninfected women to experience outbreaks of genital herpes. If HSV is transmitted to the infant, neonatal infection can be severe, even if it is detected and treated early. In addition, there is increased genital shedding of HIV in those with active genital HSV lesions. Some experts recommend obtaining HSV-2 serologies in a woman whose clinical history is unclear. Treatment for symptomatic HSV infections should be offered during pregnancy, and suppressive therapy should be given to women with frequent recurrences. If a woman has an active outbreak of genital HSV or experiences prodromal symptoms at the time of labor or membrane rupture, delivery by cesarean section is indicated. Prophylaxis with oral acyclovir late in pregnancy to prevent neonatal herpes transmission is controversial and is not recommended routinely.

Tuberculosis

Prophylaxis is recommended for any woman with a positive PPD skin test result (≥5 mm induration), a positive IGRA result, or a history of exposure to someone with active tuberculosis, after active disease has been ruled out. Because of concern about possible teratogenicity from drug exposure, clinicians may choose to delay prophylaxis until after the first trimester. Patients receiving isoniazid also should receive pyridoxine to reduce the risk of neurotoxicity.

Toxoplasmosis

All HIV-infected persons should be tested for IgG antibodies to Toxoplasmasoon after HIV diagnosis, and this should be a part of antenatal testing for pregnant women with HIV infection. Women with a negative IgG titer should be counseled to avoid exposure to Toxoplasma(e.g., by avoiding raw or undercooked meats, unwashed or uncooked vegetables, and cat feces). Women with previous exposure to Toxoplasma (positive IgG titer) should be given prophylaxis during pregnancy, if the CD4 count is <100 cells/µL. For women who require prophylaxis, trimethoprim-sulfamethoxazole is the preferred agent; some specialists advise against giving pyrimethamine during pregnancy. If secondary prophylaxis is used to prevent recurrence of toxoplasmosis, sulfadiazine should not be used, as it is contraindicated for use during pregnancy

Antiretroviral Therapy

Current U.S. Public Health Service guidelines recommend treating HIV infection in all pregnant women, using the same principles and modalities as used for nonpregnant individuals. HIV-infected pregnant women should receive potent combination ART regimens comprising at least three ARVs. The use of zidovudine (ZDV) prophylaxis alone (monotherapy) is not recommended but may be considered for the few women whose HIV RNA levels are <1,000 cells/µL on no ART and who decline combination ART. The choice of ARV regimen should be based on what is likely to be optimal for the woman's health, the potential effect on the fetus and infant, resistance test results, the woman's previous experience, if any, with ART, and her stage of pregnancy. ARV resistance testing should be performed before initiating or changing therapy. ZDV should be included in the regimens of all pregnant women unless there is severe toxicity or documented drug resistance. ARV agents with known teratogenic effects, such as efavirenz, should be avoided, especially in the first trimester. Women who do not need ART for their own health and are taking ART only for the prevention of perinatal transmission may delay initiation of therapy until after the first trimester. This is a period of rapid organogenesis, and there is an increased risk of birth defects if teratogen exposure occurs. For women already taking ART at the time they become pregnant, the regimen should be reevaluated for its appropriateness during pregnancy to avoid potentially toxic medications and to ensure maximal virologic suppression. The ART regimen may be changed if necessary, but should continue without interruption. Discontinuation of ART could lead to an increase in viral load, which could result in a decline in immune status and an acceleration of disease progression, thereby increasing the risk of HIV transmission to the fetus.

For further information about ART during pregnancy, see chapter Reducing Maternal-Infant HIV Transmissionand the DHHS Perinatal ARV Guidelines. The Guidelinesinclude recommendations regarding ARV regimens, modes of delivery (vaginal vs. cesarean section), and potential adverse events, as well as a detailed discussion of individual ARV agents. Additionally, the treatment of pregnant women with HIV/HBV coinfection and HIV/HCV coinfection is discussed.

Antiretroviral Pregnancy Registry

To improve tracking of pregnancy-related adverse events and fetal effects, an Antiretroviral Pregnancy Registry has been established as a collaborative project among the pharmaceutical industry, pediatric and obstetric providers, the CDC, and the National Institutes of Health. The registry collects observational data on HIV-infected pregnant women taking ARV medications to determine whether patterns of fetal or neonatal abnormalities occur. Pregnant women taking ARVs can be placed in this confidential follow-up study by calling 800-258-4263, 8:30 a.m. to 5:30 p.m. eastern time; the fax number is 800-800-1052. Information is confidential and patients' names are not used. Providers are encouraged to add to the available information on fetal risk by using this registry at first contact with a pregnant woman receiving ART. More information can be obtained at the registry website.

Pregnancy-Specific Complications and Management

Nutrition risk and inadequate weight gain

Maternal nutrition and weight must be monitored throughout the pregnancy. A food diary may be a useful tool in assessing intake, and nutritional counseling is recommended.

Nausea and vomiting

Women with signs of dehydration should be assessed and treated appropriately in collaboration with the obstetrician or nurse/midwife. Any medication used for nausea and vomiting must be assessed for drug-drug interactions with all HIV-related medications the patient is taking.

Hyperglycemia

Pregnancy is a risk factor for hyperglycemia, and women treated with PIs may have an even higher risk of glucose intolerance than other pregnant women and must be monitored carefully. New-onset hyperglycemia and diabetes mellitus, and exacerbation of existing diabetes, all have been reported in patients taking PIs. Clinicians should educate women taking PIs about the symptoms of hyperglycemia and closely monitor glucose levels. Some clinicians check glucose tolerance at 20-24 weeks and again at 30-34 weeks if the woman is taking PIs. The newborn should be checked for neonatal hypoglycemia at 1 and 4 hours after birth.

Lactic acidosis

Lactic acidosis is a rare but life-threatening complication that has been reported in pregnant women taking nucleoside reverse transcriptase inhibitors, particularly didanosine and stavudine. The combination of didanosine and stavudine should be avoided during pregnancy. Clinical suspicion of lactic acidosis should be prompted by vague symptoms such as malaise, nausea, or abdominal discomfort or pain. Lactate levels, electrolytes, and liver function should be monitored carefully, including monthly in the third trimester.

Hyperbilirubinemia

Women taking atazanavir or indinavir frequently develop elevated indirect bilirubin, but it is not known whether treatment during pregnancy exacerbates physiologic hyperbilirubinemia in newborns. Women who are taking indinavir may have an increased risk of nephrolithiasis, but evidence of harm to their newborns has not been demonstrated.

Pain management

Pain management during labor and delivery may be complicated by drug interactions with ARV agents and by the higher medication tolerance in women who have addictions. Additional pain medication may be needed for women with histories of drug use

Invasive perinatal procedures

The risk of HIV transmission to the fetus during invasive procedures (e.g., amniocentesis, chorionic villus sampling, and percutaneous or umbilical cord blood sampling) must be weighed carefully against the possible benefits of these procedures. Current DHHS guidelines suggest that women undergoing such procedures should be on effective ART, preferably with undetectable HIV RNA. The use of fetal scalp electrodes and artificial rupture of membranes should be avoided if possible, and forceps or vacuum extractors and episiotomy should be used only if there are clear obstetric indications.

Postpartum considerations

Because HIV can be transmitted to the infant through breast-feeding, breast-feeding is contraindicated in the United States and other resource-adequate countries where safe replacement feeding is available. Breast-feeding information should be removed from patient educational material pertaining to labor and delivery. Breast binding and ice packs can be used as needed to reduce lactation discomfort. Clinicians should recognize that women in some cultural groups are expected to breast-feed and they may need additional support to use formula rather than breast-feed.

ART should be continued as indicated by the DHHS Perinatal ARV Guidelines. Maternal and infant medication adherence must be discussed with the new mother. Adherence barriers for the mother during the postpartum period may be different from those during pregnancy (e.g., because of changes in daily routine, sleep/wake cycles, and meals).

New mothers should be observed carefully for signs of bleeding or infection.

If the mother's glucose tolerance test was abnormal during pregnancy, she should be reevaluated (by 2-hour glucose tolerance test) 6 weeks postpartum and should be screened yearly for diabetes.

At the infant's 2-week follow-up visit, the HIV pediatric clinician should address the mother's concerns, screen for postpartum depression, assess adherence to her own and the infant's ARV medications, and ensure follow-up for the 6-week postpartum visit with the obstetric provider and soon thereafter with the primary HIV care provider. These visits provide an opportunity to address the woman's contraceptive needs and options, if this was not done previously (see chapter Health Care of HIV-Infected Women Through the Life Cycle).

Contraception

Many contraceptive choices are available for HIV-infected women; considerations are discussed in chapter Health Care of HIV-Infected Women Through the Life Cycle. Depending on the woman's risk factors, consistent condom use should be emphasized, with or without other methods of contraception, to prevent the transmission of HIV and the acquisition or transmission of other STIs.

Patient Education

• Reinforce regularly and clearly the notion that, when the mother cares for herself, she is caring for her infant. Talk with the patient about stress, the importance of adequate mild-to-moderate exercise, and sufficient rest.
• Emphasize that regular prenatal care is extremely important to prevent complications of pregnancy.
• Use of a prenatal vitamin supplement is important, but cannot replace healthy food intake. Develop a plan with the patient for attaining the desired weight gain during pregnancy, while maintaining a healthy nutritional intake.
• Cigarette, alcohol, and drug use contribute to poor maternal nutrition and can harm the developing fetus. Illicit drug use increases the risk of transmitting HIV to the infant. Injection drug use can transmit HBV, HCV, and CMV to the mother and to the baby. Encourage cessation of cigarette, alcohol, and drug use, and offer referrals for treatment, as needed.
• Be sure the woman understands all planned procedures and treatments and understands their potential risks and benefits both to herself and to the fetus.
• Discuss the risks and benefits (to the woman and fetus) of each medication to be taken during pregnancy, including those for which there are limited data on teratogenicity.
• Discuss ART as part of the strategy to reduce the risk of perinatal HIV transmission to the fetus or newborn. For women at risk, diligent use of "safer sex" during pregnancy is important for preventing transmission of STIs and CMV, which can cause more complications when HIV is present. STIs can harm fetal development and may increase the risk of HIV transmission to the baby. New genital herpes infections during pregnancy can cause severe complications and even death in neonates.
• For women with negative Toxoplasmatiters, explain the need to avoid undercooked meat, soil, and cat feces.
• Teach the pregnant woman how to obtain medical attention quickly at the first signs of OI or other complication. Discuss what to watch for and how to get help when emergencies arise in the evenings or on weekends or holidays.
• Help the patient clarify her child care options and encourage her to begin putting in place long-term child care and guardianship plans in case she becomes too sick to care for her child or children.

References

• American College of Obstetricians and Gynecologists. Immunization during pregnancy. ACOG Committee Opinion No. 282; 2003. [Registration required.]
• Anderson JR. HIV and Reproduction. In: Anderson JR, ed. A Guide to the Clinical Care of Women with HIV. Rockville, MD: Health Services and Resources Administration; 2005.
• Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry International Interim Report for 1 January 1989--31 January 2008.
• Centers for Disease Control and Prevention. Enhanced Perinatal Surveillance--Participating areas in the United States and dependent areas, 2000-2003. HIV/AIDS Surveillance Supplemental Report 2008;13(No. 4).
• Centers for Disease Control and Prevention. General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP). MMWR Recomm Rep. 2006 Dec 1;55(RR15);1-48.
• Centers for Disease Control and Prevention. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. April 10, 2009.
• Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2006. MMWR. 2006;55(No. RR-11):1-100.
• Ethics Committee of the American Society for Reproductive Medicine. Human immunodeficiency virus and infertility treatment. Fertil Steril. 2004 Sep;82 Suppl 1:S228-31.
• Minkoff H. Human immunodeficiency virus infection in pregnancy. Obstet Gynecol. 2003 Apr;101(4):797-810.
• U.S. Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. January 10, 2011.
• U.S. Department of Health and Human Services. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. May 24, 2010.