Care of HIV-Infected Pregnant Women

Ideally, the evaluation of reproductive issues with an HIV-infected woman begins before pregnancy. The preconception evaluation should include the following elements:

	Reproductive history, including number of pregnancies, number of partners, pregnancies with each partner, and outcomes of each pregnancy
	Length of relationship with current partner, HIV serostatus of partner, and couple's sexual history, including condom use and sexual decision making or control of reproductive choices
	Patient's and partner's reproductive desires, and discussion of options

Any history of infertility or low fertility in either the patient or her partner also should be evaluated and discussed, including current information on gamete donation, other assisted reproductive techniques, and adoption. For a woman (or a couple) who has decided to try to conceive, several issues must be considered. Prominent among these is the HIV serostatus of both partners. If HIV infection is present in only one of the partners, the risk of transmission to the uninfected partner and techniques to minimize the risk should be discussed. (For further discussion and patient-education materials for HIV-discordant couples, see Aaron and Mercurius in "References" below.)

If ART is indicated, an appropriate regimen should be started before pregnancy, avoiding agents with increased risk for teratogenicity (eg, efavirenz), hepatotoxicity (eg, nevirapine), or metabolic complications such as lactic acidosis (eg, didanosine, stavudine, and zalcitabine). See chapter Reducing Maternal-Infant HIV Transmission and the 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. Centers for Disease Control and Prevention. October 12, 2006. 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 antiretroviral (ARV) or another drug, should be avoided in women who are intending to become pregnant or are at risk of pregnancy. Certain medications (eg, 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).

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 treated with 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 woman 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 vaccinations as indicated for persons with HIV infection (eg, pneumococcus vaccination) (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 possible risk. Consult with an HIV or obstetric specialist, a pharmacist, or the drug labeling information before prescribing medications for pregnant women.

Other evaluation and support 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 orally once daily) to reduce the risk of fetal neural tube defects. Pregnant women who are taking trimethoprim-sulfamethoxazole (Septra, Bactrim, cotrimoxazole) and women who may become pregnant who are taking trimethoprim-sulfamethoxazole should be given higher doses of folate. Some experts recommend a folate dose of 4 mg daily for women receiving trimethoprim-sulfamethoxazole.
	Screening for psychiatric and neurologic disease
	Counseling about the risks of tobacco smoking; smoking cessation support as indicated
	Counseling about the risks of alcohol or drug use and support for discontinuation of these substances as needed
	Domestic violence screening
	Review of medications, including over-the-counter and nutritional agents; discontinuation of medications with the potential for fetal harm
	Immunizations (eg, influenza, hepatitis B) as indicated
	Institution of the standard measures for evaluation and management (eg, assessment of reproductive and familial genetic history, screening for infectious diseases or sexually transmitted diseases [STDs])
	Planning for maternal-fetal medicine consultation, if desired or indicated
	Selection of effective and appropriate postpartum contraceptive methods if desired

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.

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 (such as measles/mumps/rubella) are contraindicated, and others should be given only if the anticipated benefit of the vaccination outweighs its possible 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 4.

Table 4. Immunizations and Postexposure Prophylaxis in Pregnant Women with HIV Infection

Table 4. Immunizations and Postexposure Prophylaxis in Pregnant Women with HIV Infection Immunization Comment Hepatitis A virus (HAV) Recommended for susceptible patients at high risk of infection, those with chronic HBV or HCV, those traveling to endemic areas, injection drug users, or in the setting of a community outbreak Hepatitis B virus (HBV) Generally recommended for susceptible patients Influenza Generally recommended; give before flu season Measles/Mumps/Rubella (MMR) Contraindicated Pneumococcus Generally recommended, repeat every 5-7 years Tetanus-diphtheria Recommended; give booster every 10 years Immune globulins (For postexposure prophylaxis in susceptible individuals) Comment Measles Recommended after measles exposure, for symptomatic HIV-infected persons Hepatitis A Recommended after exposure to a close contact or sex partner, or in case of travel to endemic areas Hyper immune globulins Comment Varicella-zoster virus immune globulin (VZIG) Recommended after significant exposure to varicella-zoster virus (give within 96 hours) Hepatitis B immune globulin (HBIG) Recommended after needlestick or sexual exposure to a person with hepatitis B infection

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 due 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 USPHS and the Infectious Diseases Society of America, which give special consideration to pregnant women for each OI discussed. (Guidelines for Prevention of Opportunistic Infections among HIV-Infected Persons--2002. June 14, 2002.) 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 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 high doses of folate (eg, 4 mg daily) to overcome the folate antagonism of trimethoprim-sulfamethoxazole. Because neural tube development occurs very early in pregnancy, folate supplementation should be started at least 1 month before conception, if possible. Genital herpes Women with HIV infection are more likely than HIV-uninfected women to experience outbreaks of herpes. If herpes simplex virus (HSV) is transmitted to the infant, neonatal infection can be severe, even if it is detected and treated early. Strongly consider 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 routinely recommended. Tuberculosis Prophylaxis is recommended for any woman with either a positive purified protein derivative (PPD) skin test (≥5 mm induration) or a history of exposure to 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 immunoglobulin G (IgG) antibodies to Toxoplasma soon 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 (eg, by avoiding raw or undercooked meats, unwashed or uncooked vegetables, and cat feces). Women with previous exposure to Toxoplasma (positive IgG titer) may be given prophylaxis during pregnancy, if indicated. For women who require prophylaxis, trimethoprim-sulfamethoxazole is the preferred agent; some specialists advise against giving pyrimethamine during pregnancy.

Current USPHS guidelines for the use of ARV agents in pregnant women with HIV infection recommend treating HIV infection in pregnant women using the same principles and modalities as for nonpregnant individuals. The 3-part zidovudine (ZDV) regimen (antenatal, intrapartum, and neonatal) should be recommended as the minimum intervention to reduce the risk of perinatal HIV transmission. In addition to the 3-part ZDV regimen, the guidelines recommend offering effective combination ART to all pregnant women to maximally suppress viral replication, minimize the risk of developing resistant virus, and reduce the risk of perinatal transmission. The choice of ARV regimen should take into account the optimal regimen for the woman's health, the potential effect on the fetus and infant, the woman's previous experience, if any, with ARV treatment, and her stage of pregnancy. In most cases, the regimen should include ZDV, if possible. ARV agents with known teratogenic effects, such as efavirenz, should be avoided, especially in the first trimester. Some clients and HIV care providers may elect to withhold ARV therapies during the first trimester, because this is a period of rapid organogenesis and an increased risk of birth defects if teratogen exposure occurs. For women already taking ART at the time they become pregnant, the ARV regimen should be reevaluated for its appropriateness during pregnancy to avoid potentially toxic medications and to ensure maximal virologic suppression. If a decision is made to interrupt ART during the first trimester, the woman should be instructed how and when to stop and to restart ART and should be made aware of the risk of viral rebound during the ARV interruption.

Discussion of treatment options should include the known and unknown effects of ARV drugs on the fetus and newborn, recommendations for the woman's health, and the known efficacy of ZDV in preventing perinatal transmission. Recommendations should be noncoercive, and the woman herself must make the final decision regarding the use of ARV drugs. A decision to decline ART should not result in punitive action or denial of care; nor should ART be denied to any woman who wishes to minimize the fetus's exposure to drugs and therefore chooses to receive only ZDV to reduce the risk of perinatal transmission. The woman should be informed that ZDV alone does not reduce the baby's HIV risk as much as a potent triple-drug therapy, and also that monotherapy with any ARV drug confers a risk of drug resistance that may affect the success of future treatment for her and for the infant (if HIV infected).

The USPHS Perinatal ARV Guidelines are updated regularly as clinical trial results are reported and ARVs are approved by the U.S. Food and Drug Administration. The guidelines include 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. Pregnant women with HIV infection should be managed as a collaboration between an HIV specialist and the obstetric provider.

For further information about ARV treatment during pregnancy, see the chapter Reducing Maternal-Infant HIV Transmission and the USPHS Perinatal ARV Guidelines.

Antiretroviral Pregnancy Registry

To improve tracking of pregnancy-related adverse effects 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 am to 5:30 pm 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 taking ARVs. More information can be obtained at http://www.APRegistry.com.

The risk of HIV infection of the fetus during invasive procedures (eg, amniocentesis, chorionic villus sampling, percutaneous or umbilical cord blood sampling) must be balanced against the possible benefits of these procedures. Invasive procedures should be performed only after discussion with and consent from the pregnant woman.

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 USPHS 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 (eg, 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 2-week postpartum follow-up visit, the clinician should address the patient's concerns, screen for postpartum depression, assess adherence to her own and the infant's ARV medications, and ensure follow-up with the primary HIV care provider, pediatrician, and obstetric provider. This visit also affords an opportunity to address the woman's contraceptive needs and options, if this was not done previously.

Contraception

Many contraceptive choices are available for HIV-infected women; some considerations are discussed in Table 5. 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 STDs. Table 5. Advantages and Disadvantages of Various Contraceptives Table 5. Advantages and Disadvantages of Various Contraceptives * See chapter Antiretroviral Medications and Oral Contraceptive Agents and U.S. Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. October 10, 2006. Contraceptive Type Advantages Disadvantages Barrier Methods Male and female condom Protect against transmission of HIV and STDs Requires partner cooperation and correct technique High failure rate when used incorrectly Diaphragm and cervical cap Requires partner cooperation and correct technique High failure rate when used incorrectly Sponge Does not prevent STD or HIV transmission Hormonal Methods Do not prevent STD or HIV transmission Oral* Very effective Lighter menstrual flow May have significant drug-drug interactions with protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) that may affect the efficacy and toxicity of estradiol and norethindrone, and of certain PIs* Consider alternative methods for women taking PIs or NNRTIs Some concern about increased cervical proviral shedding Injectable depot medroxyprogesterone acetate (DMPA, Depo-Provera) Effective contraception for 3 months Possible increased risk of genital tract HIV shedding Long-term concern about osteoporosis Transdermal/Patch Effective Lighter menstrual flow No studies to document pharmacokinetic interactions, but possible significance Possible increased risk of HIV viral shedding Vaginal ring Effective Lighter menstrual flow No studies to document pharmacokinetic interactions, but possible significance Possible increased risk of HIV viral shedding Intrauterine devices (IUDs) Effective for long-term use No evidence of increased HIV viral shedding Possible blood loss with Copper T IUD Surgical Methods Bilateral tubal ligation (female) Effective; permanent Does not prevent STD or HIV transmission No future fertility (usually not reversible) Vasectomy (male) Effective; permanent Does not prevent STD or HIV transmission No future fertility (usually not reversible) Spermicides Spermicides Not currently recommended Nonoxynol-9 increases risk of HIV transmission Do not prevent STD or HIV transmission * See chapter Antiretroviral Medications and Oral Contraceptive Agents and U.S. Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. October 10, 2006.