HIV transmission during pregnancy

INTRODUCTION — The most common way for infants to acquire the human immunodeficiency virus (HIV) is from the mother during pregnancy, labor and delivery, and, to a lesser degree, through breastfeeding. This mother-to-child, also called perinatal, transmission of HIV resulted in the birth of approximately 1,750 HIV-infected infants in the United States each year until 1994, when it was recognized that the use of zidovudine (ZDV) could reduce transmission by nearly 70 percent. The number of AIDS cases (AIDS being the most severe manifestation of HIV infection) diagnosed among infants infected through perinatal transmission has markedly declined since 1994.

While use of medications has decreased transmission of HIV from mothers to babies, not all women are aware that they are infected with HIV. Therefore, experts strongly recommend that all pregnant women undergo screening for HIV infection and receive information, support, and counseling concerning their options. (See "Patient information: Testing for HIV").

This topic review discusses factors that can reduce perinatal HIV transmission. Many of the treatments available in the developed countries are not accessible in the rest of the world. While trials of modified therapy and other types of interventions are being performed in the developing world, they will not be reviewed here since women in the United States have other options.

CARE DURING PREGNANCY — The treatment of an HIV-infected pregnant woman usually involves an HIV specialist, primary care provider, pregnancy care provider, and the woman herself.

Initial evaluation — The initial evaluation of an HIV-infected woman who is (or is considering becoming) pregnant may include assessment of the status of her HIV disease, recommendations regarding treatments, and discussions about ways to lower the risk of mother-to-child HIV transmission. More specifically, the initial assessment often includes the following: Laboratory tests to assess the current status of HIV disease, such as blood studies to determine the viral load of HIV (quantity of RNA) and the number of CD4 or helper T cells, which are important for the individual's immune system. These numbers affect the choice of treatments and the likelihood of HIV transmission during pregnancy or delivery. Review of medications for prevention of opportunistic infections, such as Pneumocystis carinii pneumonia (PCP) or Mycobacterium avium complex (MAC). These medicines are usually given to patients with CD4 counts less than 200/µL. The medications used may depend upon the stage of pregnancy and the potentially harmful effects of certain drugs on the developing fetus. A history of any prior or current antiretroviral therapy. The drugs a patient currently receives, or has taken before, influence not only the current HIV viral load and CD4 cells, but also the degree of sensitivity of the virus to these types of drugs. In general, decisions should be based on the same criteria as for non-pregnant individuals, except that the potential impact of medications on the developing fetus are considered (see "ZDV regimen" below). Consideration of the antiretroviral medications needed for treatment of the mother's HIV infection. Combination antiretroviral therapy using three antiretroviral drugs, also called highly active antiretroviral therapy or "HAART", is currently the standard for treatment of non-pregnant individuals and for pregnant women who require treatment as well. When possible, ZDV is included as a component of maternal HAART therapy. However, if ZDV is not used during pregnancy, it is still recommended for the woman during labor and for the newborn for six weeks after birth. Consideration of the potentially harmful (teratogenic) effects of certain antiretroviral medications on the growth and development of the fetus. A teratogen is any agent, substance, or process that may interfere with proper development before birth, leading to physical abnormalities in the developing fetus. The fetus is most susceptible to potential teratogenic effects during the first 10 weeks of gestation. Discussions about the importance of appropriate support services for optimal maternal and infant health. Depending upon individual circumstances and special needs, some HIV-infected women require drug abuse treatment, mental health services, and/or other support services. Such discussions should also include long-term planning for care of the child in the event of maternal illness.

During pregnancy Blood should be drawn for CD4 cell count and viral load every three to four months to determine the need to start or change antiretroviral therapy for maternal HIV and prevention of PCP or MAC. Long-term plans should be made to ensure the women's continuity of care and ongoing adherence to appropriate antiretroviral therapies for her own health Blood tests, such as liver function testing and screening for diabetes, are recommended to detect possible complications of antiretroviral therapy. More intensive testing may be required for those receiving combination antiretroviral therapy. Routine fetal monitoring is recommended for women receiving only ZDV therapy. However, more intensive monitoring is recommended for women receiving combination antiretroviral therapy. This usually includes a level II ultrasound during the second trimester and ongoing assessment of fetal growth and development in the third trimester.

MINIMIZING TRANSMISSION RISK — There are important behavior changes that a woman can make to improve her health and reduce the risk of perinatal HIV transmission. These include discontinuing cigarette smoking, refraining from injection drug use and illegal drugs (such as cocaine or heroin), and avoiding unprotected sexual intercourse.

Labor Whenever possible, invasive procedures that might increase mother-to-child transmission of HIV should be avoided, such as fetal blood sampling, invasive fetal monitoring (eg, scalp electrodes), and artificial rupture of membranes. Because of an increased risk of HIV transmission as the time between membrane rupture ("water breaking") and delivery increases, medication may be needed to speed labor. For a woman whose cervix closed, labor can be induced with a medication applied directly to the cervix, which causes it to open (dilate). Some women, including those whose cervix has begun to dilate, will also require an intravenous medication, oxytocin, which stimulates the uterus to contract; uterine contractions further stimulate the cervix to open and thin. If induction of labor does not completely open and thin the cervix, or if complications develop that require the baby to be delivered quickly, a cesarean delivery is usually performed. Intrapartum ZDV prophylaxis should be given regardless of the mode of delivery, since the available data indicate that ZDV provides an additional protective effect against HIV transmission. Intravenous ZDV should begin three hours prior to a scheduled cesarean delivery Other antiretroviral drugs should be continued on schedule during labor or preoperatively to provide maximal protection and to minimize the risk of developing drug resistance. Episiotomy is an incision (cut) sometimes made during delivery to widen the vaginal opening. Avoiding episiotomy may decrease exposure of the infant to maternal blood. The infant should be washed before any blood is drawn, injections given, or other invasive procedures performed.

Delivery — A cesarean section is the surgical delivery of a baby by incision through the mother's abdomen and uterus. Cesarean section performed before labor begins may provide some protection against perinatal HIV transmission by decreasing or eliminating exposure to HIV-infected blood and secretions in the birth canal during delivery. It may also prevent small quantities of maternal blood from passing into the fetal circulation from the placenta during contractions, also known as "microtransfusions".

Cesarean section performed before labor decreases the likelihood of perinatal HIV transmission by about 50 percent. The combination of elective cesarean section and therapy with ZDV (ie, during pregnancy, labor, and in the newborn) reduces HIV transmission by approximately 85 percent when compared to other methods of delivery in women who have taken no antiretroviral medications. (See "Patient information: Cesarean delivery"). Summary — The American College of Obstetrics and Gynecology recommends that elective cesarean delivery be discussed and recommended for all HIV-infected pregnant women with viral loads above 1000 copies/mL. In this situation, ceserean section would be scheduled at 38 weeks of gestation. In women at very low risk for transmission, such as those with a low or undetectable viral load, the benefit of elective cesarean section may be small.

The potential benefit of elective cesarean section should be discussed with all HIV-infected pregnant women, but the final decision should be based upon a woman's individual circumstances. ZDV prophylactic therapy is recommended for both the mother and baby, regardless of the method of delivery.

Breastfeeding — Breastfeeding can clearly transmit HIV infection to the infant. In one study of over 600 mother-infant pairs from Malawi, the risk of transmitting HIV to the infant through breastmilk was 7.0 percent for infants who breastfed for one year and 10.3 percent for infants who breastfed for up to two years.

In the United States, clean water and infant formulas are readily available, and are safe alternatives to breastfeeding. Therefore, the United States Public Health Service recommends that HIV-infected mothers not breastfeed their babies. The same advice cannot be given to women in the developing world because safe alternatives to breastmilk (eg, clean water and formula) may not be consistently available.

ZDV REGIMEN — The following is the current ZDV schedule recommeded for a pregnant women during pregnancy, labor, and delivery, and for her newborn after delivery: During pregnancy, ZDV should be started anytime from the 14th week of gestation through the 34th week, and then continued for the rest of the pregnancy. The dose of ZDV is 200 mg by mouth three times a day or 300 mg twice a day. ZDV is not given during the first trimester due to theoretical concerns regarding the potentially harmful effects for the fetus. During labor and delivery, the woman is given ZDV continuously through an IV. The newborn receives ZDV syrup (2 mg/kg by mouth four times a day). The first dose should be given within the first 8 to 12 hours after birth and continued for the first six weeks of life. A lower dose is usually given to premature infants, which is gradually increased during the six weeks.

Although ZDV significantly reduces the risk of perinatal transmission, the use of one antiretroviral medication is not optimal for treatment of HIV infection. Combination antiretroviral therapy with three antiretroviral drugs, generally two nucleoside analogue reverse transcriptase inhibitors and a protease inhibitor or non-nucleoside reverse transcriptase inhibitor, is the currently recommended standard treatment for nonpregnant HIV-1-infected adults.

However, the benefit of appropriate treatment for the woman's HIV must be balanced with the potential risk of antiretroviral medications on the growth and development of the fetus. Information regarding safety during pregnancy is not available for all of these medications, and thus the "best" treatment must be chosen based upon currently available information.

There are several antiretroviral drugs that should not be used in pregnancy: these include efavirenz; the combination d4T/ddI; nevirapine in women with CD4 count >250/mm3; zalcitabine (ddC) and delavirdine.

Benefits/risks of ZDV ZDV therapy is well-tolerated in the short-term by the mother and the infant; a mild, reversible anemia (decreased number of red blood cells) may be seen in the infant during the first six weeks of life. ZDV does not appear to increase the risk of birth defects. However, further studies are necessary to draw definitive conclusions. Longer follow-up will be needed to determine if there are any long-term risks for women and children who have received ZDV. Currently, the known benefit of ZDV outweighs any theoretical risks.

Regimens during pregnancy

For women NOT taking antiretroviral therapy — Recommendations for pregnant women who are not currently taking any antiretroviral medication when pregnancy is discovered include the following: The three-part ZDV regimen is recommended for all pregnant women with HIV infection. ZDV is usually started after 14 weeks and before 34 weeks of gestation. Combining the three-part ZDV regimen with additional antiretroviral drugs (a multi-drug HAART regimen) is recommended for HIV-infected pregnant women who have HIV RNA ("viral load") levels >1,000 copies/mL. The risk of mother to child transmission is markedly decreased when HIV RNA levels are reduced to <1,000, and this is best achieved with a combination antiretroviral regimen. Women with HIV RNA levels under 1,000 may choose to take a combination HAART regimen or to take only ZDV. Women who are first seen during the first trimester may wish to delay starting antiretroviral treatment until after the first trimester. For women who have taken no antiretroviral medications during pregnancy, including ZDV, there are several regimens that can be given during labor to reduce the risk of perinatal transmission. Although these are not as effective as the full three-part ZDV regimen, they are better than no treatment.

When a woman has not taken ZDV during pregnancy, labor, or delivery, the newborn should receive a six-week course of ZDV, beginning as soon as possible after birth, preferably within 6 to 12 hours. Alternately, a combination of antiretroviral drugs may be given to the infant, depending upon the status of the mother.

For women taking antiretroviral therapy — Recommendations for these women include the following: If pregnancy is recognized after the first trimester, the current antiretroviral therapy can be continued. If pregnancy is recognized during the first trimester, the physician and patient should discuss the potential benefits and risks of continuing the treatment. If therapy is temporarily discontinued, all antiretroviral medications should be stopped at the same time and reintroduced together after the first trimester; this helps to minimize the risk of developing resistance to such drugs. If the current regimen does not currently include ZDV, it may be recommended after 14 weeks gestation. ZDV therapy is also typically recommended for the woman during labor and delivery, and for the newborn after delivery, regardless of the antiretroviral therapies used during pregnancy.

FOLLOW UP CARE

For newborns and infants — After the infant is born, monitoring for side effects of antiretroviral medications should continue. In addtion, the baby should be screened for HIV. A complete blood count prior to the administration of ZDV. This blood test measures the cellular components of the blood (white blood cells, red blood cells, and platelets). Repeat testing to measure hemoglobin (the oxygen-carrying component of the blood) following completion of the six-week ZDV regimen and at 12 weeks of age. More intensive monitoring may be required for infants who have anemia at birth, who were born prematurely (before 37 weeks gestation), or whose mothers received combination antiretroviral therapy. Infants should be screened for HIV infection at birth, two weeks, one to two months, and three to six months of age, looking for HIV DNA (the genetic material of the virus inside of lymphocytes, which are blood cells that HIV infects). Prophylaxis for PCP (eg, trimethoprim-sulfamethoxazole [Bactrim]) should be started following completion of ZDV therapy at six weeks of age because infants are at risk for acquiring this infection, even before HIV infection is diagnosed. Therapy is continued until an HIV test is negative at four months of age. If the infant is HIV-infected, this treatment should be continued.

For women after delivery — As noted above, women who only received ZDV during pregnancy need to be evaluated after delivery to determine if ongoing antiretroviral therapy is needed. In addition, ongoing comprehensive care and supportive services, including HIV-related medical care, psychosocial support, and assistance with family planning and contraception, should be offered to all women.

Long-term follow-up of children Infants and children who were exposed to antiretroviral drugs during their mother's pregnancy should receive ongoing follow-up. Data on uninfected infants exposed to ZDV are reassuring and show no abnormalities in growth, the immune system, brain function and tumor development for six years. However, data are insufficient to determine whether these children have a long-term risk for organ system abnormalities or cancer. Children exposed to antiretroviral agents should have at least a yearly physical examination, including a gynecological evaluation for older adolescent girls.

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. The National Institute of Child Health and Human Development

(301) 496-5133
(www.nlm.nih.gov/medlineplus)
Centers for Disease Control and Prevention (CDC)

Phone: (404) 639-3534
Toll-free: (800) 311-3435
(www.cdc.gov)
CDC (Centers for Disease Control and Prevention) National AIDS Hotline

English: (800) 342-2437
Spanish: (800) 344-7432
CDC National Prevention Information Network (NPIN)

Toll-free: (800) 458-5231
E-mail: info@cdcnpin.org
National Institute of Allergy and Infectious Diseases (NIAID)

Phone: (301) 496-5717
(www.niaid.nih.gov)
AIDS Clinical Trials Information Service (ACTIS)

Toll-free: (800) 874-2572
E-mail: actis@actis.org
(www.actis.org)
HIV/AIDS Treatment Information Service

Toll-free: (800) 448-0440
E-mail: atis@hivatis.org
(www.hivatis.org)


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