Assuring Optimal Management of HIV Infection During Pregnancy

Peter S. Bernstein, MD, MPH

Disclosures

June 28, 2002

Introduction

Since 1994, when the results of the Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 revolutionized the care of pregnant women infected with human immunodeficiency virus (HIV), the care of these patients has dramatically changed many times over. PACTG 076 documented that chemoprophylaxis with zidovudine (ZDV) could reduce perinatal HIV-1 transmission by nearly 70%.[1] The regimen described in that landmark paper was quickly adopted as the standard of care by the US Public Health Service; it consisted of oral ZDV initiated at 14-34 weeks of gestation, intravenous ZDV administered during labor and delivery, and oral ZDV for the neonate for 6 weeks after delivery.[2] The institution of this practice and efforts toward universal screening of pregnant women for HIV infection have contributed to the dramatic decline in perinatal transmission of HIV in the United States and other developed nations.

During the same time period, the care of people infected with HIV has also dramatically changed from one of supportive care of individuals with a terminal illness to aggressive care of an often manageable chronic disease. The introduction of highly active antiretroviral therapy (HAART) has changed the care of those infected with HIV. Combination therapy with drugs from different classes of antiretroviral medications, such as protease inhibitors and nucleoside analogue reverse transcriptase inhibitors, can suppress viral replication to the point that plasma viral RNA is undetectable and allow for some level of reconstitution of the individual's immune system.

These advances, together with a growing understanding of the mechanism of perinatal transmission of HIV infection, have provided tremendous opportunity for the management of pregnant women who are infected with the virus, but they have also greatly complicated their care. Goals of therapy during pregnancy are 2-fold as a result: (1) to provide appropriate care for the woman's HIV infection, and (2) to attempt to reduce the risk of vertical transmission to the neonate. Choice of antiretroviral medications has to be made not only with these considerations in mind, but also with care taken not to jeopardize maternal or fetal health.

Issues in pregnancy include the potential harmful effects of antiretroviral medications on the mother and fetus, including their potential teratogenicity and possible association with pregnancy outcomes such as preterm delivery and growth restriction. More recent evidence seems to suggest that while these risks may not be great, they cannot be excluded.[3]

For the pregnant woman, the issues surrounding the management of her HIV infection and pregnancy are also complex. Decisions for the initiation of antiretroviral therapy should be the same for pregnant women as they are for nonpregnant women, with consideration of the potential impact of these medications on the developing fetus. Modifications of this therapy should similarly be guided by the woman's condition, with a recommendation of the inclusion of the 3-part ZDV prophylaxis regimen.

Discussions with the patient should emphasize the importance of careful compliance with the prescribed regimen and consideration of other factors that may influence her ability to adhere to the regimen, such as social issues and expected nausea and vomiting related to pregnancy. Failure to strictly comply with the regimen can encourage the development of virus that is resistant to a whole range of antiretroviral medications, and this may have significant ramifications not only for the woman herself, but also for her child in the event that he or she becomes infected with HIV. As a result, additional support services should be made available to patients to help them stick to their prescribed regimens, including social support, mental health services, nutritional counseling, and substance abuse cessation interventions. Access to a pharmacist with expertise in the use of these medications can be especially useful.

The 3-part ZDV prophylaxis regimen initiated after the first trimester should be recommended to all pregnant women with HIV infection regardless of the stage of their condition as part of an effort to reduce perinatal transmission. Combination therapy is recommended for any infected woman whose clinical or virologic status requires therapy or who has an HIV RNA count > 1000 copies/mL. As with the ZDV regimen, this can be delayed or suspended until after the first trimester. Combination therapy that lowers the viral load to a level below 1000 copies/mL, in addition to having maternal benefits, may also further reduce risk of vertical transmission.

Even for pregnant woman with HIV infection and no indication for antiretroviral therapy (eg, their viral load is < 1000 copies/mL) other than the need to prevent vertical transmission, decisions about antiretroviral therapy are not straightforward. Women in this situation should be counseled about the benefits of ZDV prophylaxis for prevention of vertical transmission of HIV infection. However, time-limited use of ZDV alone during pregnancy is controversial because of concerns about the development of viral resistance. As a result, standard combination therapy should be offered as well, as should dual therapy with nucleoside analogues (even though this is not typically offered to nonpregnant HIV-infected individuals because of its potential for inadequate viral suppression and the development of viral resistance). Women on combination antiretroviral therapy may have very low rates of vertical transmission independent of their viral load at the time of delivery. This may reflect transplacental passage of the drugs, providing pre-exposure prophylaxis to the fetus.

Careful management of women infected with HIV is also important during labor and at delivery in order to minimize risk of vertical transmission and reduce the potential for maternal and neonatal complications. The HIV-infected woman should be provided with the most up-to-date information on the use of antiretroviral therapy, mode of delivery, and other issues, such as whether to undergo cesarean delivery, and then should be encouraged to make her own decisions. For example, although recommendations issued by such organizations as the American College of Obstetricians and Gynecologists[4] are clear about which HIV-positive women should undergo cesarean delivery to reduce the risk of vertical transmission, the decision for an individual woman may be less obvious. HIV-infected pregnant women need to balance the risks of transmission to the infant against the risks they themselves face, especially in light of the stage of their disease. Given the rapidly changing knowledge and guidelines for the care of HIV-infected pregnant women, their care should be undertaken only by obstetric providers well versed in the latest recommendations for their management in consultation with a provider prepared to furnish these women with long-term HIV care. Current guidelines are regularly made available on the Internet at www.hivatis.org. Additionally, since so little is known about the optimal use of antiretroviral medications in pregnancy, efforts should be made to enroll these patients in research trials and to have them reported to registries, which monitor for the possible teratogenicity of prenatal exposure to anti-HIV mediations (for example, the Antiretroviral Pregnancy Registry is a collaborative project undertaken by pharmaceutical companies and a clinician advisory board).

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