MASAC Recommendation # 122
MASAC RECOMMENDATIONS CONCERNING THE USE OF ANTIRETROVIRAL DRUGS DURING PREGNANCY TO PREVENT TRANSMISSION OF HIV TO THE INFANT
The following recommendations were approved by the Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation on November 17, 2001, and adopted by the NHF Board of Directors on November 18, 2001. Much has changed since the previous MASAC Recommendation #42. Although the changes are summarized briefly below, MASAC strongly recommends that providers refer to the source document referenced below, entitled "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," for more detailed information.
Antiretroviral treatment (ART) of HIV-1 infected women should not be withheld during pregnancy unless there are known adverse effects on the mother, fetus, or infant that outweigh the benefit to the woman. Combination antiretroviral therapy is the currently recommended treatment for HIV-infected women who are not pregnant. Pregnancy should not preclude use of optimal therapeutic regimens for pregnant HIV-infected women. Antiretroviral treatment of HIV-positive pregnant women requires consideration for 1) ART of the woman's HIV infection and 2) antiretroviral chemoprophylaxis to reduce risk for perinatal HIV transmission. Antiretroviral monotherapy is suboptimal treatment for these indications; combination drug therapy is the current standard of care.
ART in Pregnant Women
Limited data are available regarding ART in pregnancy. As many as 80% of pregnant women treated with ART develop one or more adverse effects, such as anemia, nausea, vomiting, ALT or AST elevation, or hyperglycemia. About one-third of their offspring are born prematurely. Although ART side effects of mitochondrial toxicity, neuropathy, myopathy, cardiomyopathy, pancreatitis, hepatic steatosis, and lactic acidosis are more common in women, it is unknown whether these adverse events contribute to life-threatening disorders in pregnancy. Among the planned prospective studies of pregnant women are 1) a meta-analysis of multiple ACTG trials to determine risk factors for adverse pregnancy outcomes; and 2) The Antiretroviral Pregnancy Registry, which patients may be enrolled in prospectively for follow-up of teratogenicity and outcomes (800-258-4263).
PACTG 076 and Other Clinical and Epidemiologic Trials
Zidovudine (AZT) used in the peripartum period has led to a significant reduction in HIV transmission to infants (7.6% vs. 22% of untreated) with no greater risk of teratogenicity or disorders of growth, neurological development, or immunity. The finding of potential carcinogenicity of zidovudine in animals has confirmed the need for long-term follow-up. ART in HIV+ pregnant women has been associated with no adverse effect on CD4, time to HIV progression, or death, and only 3% have developed ZDV resistance. Studies to explore the maximum duration of ART needed to prevent perinatal transmission are ongoing. Epidemiological studies suggest that HIV RNA levels correlate with risk of transmission, that ZDV protects against transmission despite maternal HIV RNA level, and that transmission occurs most likely around the time of delivery.
HIV RNA Assays during Pregnancy
HIV RNA should be monitored during pregnancy at least as often as is recommended for non-pregnant HIV-infected persons; that is, every three to four months, or once each trimester. The majority of pregnant HIV-infected women experience an increase in plasma HIV RNA postpartum unrelated to zidovudine use.
Antiretroviral Chemoprophylaxis to Reduce Perinatal Transmission
The physician and patient should discuss a long-term treatment plan, including the importance of antiretroviral drugs in maternal health and in the prevention of perinatal transmission. The goal is to suppress viral load to < 1,000 copies/ml. Combination therapy regimens should be chosen from those recommended for non-pregnant adults. Dual nucleoside analogue therapy without a protease inhibitor or non-nucleoside inhibitor is not recommended because of the potential for inadequate viral suppression and emergence of resistance.
· An Antepartum Regimen should be initiated at 14-34 weeks gestation and continued throughout pregnancy. The recommended drugs include zidovudine in the PACTG 076 dosing of 100 mg five times daily or alternatively 200 mg 3 times daily or 300 mg 2 times daily.
· The Intrapartum Regimen should include during labor, intravenous zidovudine, 2 mg/kg over 1 hour, followed by 1mg/kg continuous infusion until delivery.
· The Postpartum Regimen includes oral zidovudine (syrup), 2 mg/kg given to the newborn every 6 hours for the first 6 weeks of life, beginning at 8-12 hours after birth.
Among women receiving ART at the time of pregnancy, zidovudine should be used as a component of the regimen after the first trimester whenever possible, and, if possible, it should be initiated during labor even if the woman did not take it during pregnancy. Because of known antagonism between zidovudine and stavudine, women taking the latter drug should stop it during the intravenous dosing of zidovudine (Intrapartum Regimen), or alternatively, stavudine may be used without intravenous zidovudine during this period. An ongoing study, ACTG 316, is now evaluating a two-dose nevirapine regimen, one dose to the mother at onset of labor and a single dose to the infant at 48 hours of age.
Efavirenz and hydroxyurea are teratogenic and should be avoided during the first trimester, although efavirenz is a recommended alternative to zidovudine in the peripartum period. A number of issues remain unclear at present, including the impact of prior antiretroviral drug therapy on zidovudine prophylaxis, the need for antiretroviral resistance testing, whether women receiving ART should stop it during the first 10 weeks of pregnancy, and whether other antiretroviral drugs may be as effective as zidovudine in prevention of transmission to the fetus.
Elective Cesarean Delivery to Reduce Perinatal Transmission
Studies have shown that cesarean delivery prevents HIV transmission in untreated mothers but not in women receiving effective antiretroviral therapy. If ART reduces HIV viral load to low or undetectable levels, and low levels are associated with very little likelihood of prenatal transmission, it is unlikely that performing cesarean delivery would further reduce transmission. Thus, the current recommendation is for cesarean delivery as an adjunct for prevention of perinatal transmission when the mother's HIV viral load is > 1,000 copies/ml.
1. 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. December 5, 2001. Available on the HIV/AIDS Treatment Information Service website (http://www.hivatis.org) or through 800-448-0440.
This material is provided for your general information only. NHF does not give medical advice or engage in the practice of medicine. NHF under no circumstances recommends particular treatment for specific individuals and in all cases recommends that you consult your physician or local treatment center before pursuing any course of treatment.
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