Recommendations of the U.S. Public Health Service Task Force on the Use of Zidovudine to Reduce Perinatal Transmission of Human Immuno deficiency Virus

MMWR

August 5, 1994

ZDV is assigned pregnancy category C status by the Food and Drug Administration
(FDA).* Most studies of ZDV administered to pregnant animals have not demonstrated teratogenicity. In one study, pregnant rats were administered toxic doses of
ZDV during organogenesis (i.e., equivalent to approximately 50 times the recommended daily clinical dose, based on relative body surface areas); developmental
malformations and skeletal abnormalities were observed in 12% of fetuses (14).
In humans, observational studies involving small numbers of subjects have demonstrated no apparent association of fetal malformations with antenatal ZDV use
(15-19). In ACTG Protocol 076, the incidence of congenital malformations was similar
for ZDV and placebo recipients. However, because ZDV was not administered until
after 14 weeks of gestation in this study, the potential teratogenicity of ZDV administered during the first trimester cannot be assessed. Similarly, in a recent report from
the Antiretroviral Pregnancy Registry maintained by the Wellcome Foundation and
Hoffman LaRoche in conjunction with CDC, no increase in the risk of congenital abnormalities above that expected for all pregnancies was observed among infants born to
121 prospectively registered HIV-infected women who received ZDV during pregnancy, nor was there any unusual pattern of birth defects (20).
Use of ZDV during pregnancy could be associated with the development of
ZDV-resistant virus, which may lessen the drug's therapeutic benefit for the woman
when it is needed for her own health. However, patients with early-stage HIV disease
rarely develop ZDV-resistant strains before they have received 18-24 months of continuous therapy (21). After discontinuation of ZDV therapy, an increase in ZDVsusceptible isolates has been observed in some patients who had ZDV-resistant isolates while they were receiving ZDV, although resistance to ZDV has been reported to
persist for more than a year after therapy was discontinued (22,23). Because the development of ZDV-resistant viral strains secondary to transient ZDV use during
pregnancy is a theoretical concern, considerations for the woman's future health care
should include the availability of alternative drugs for treatment of HIV infection.
GENERAL PRINCIPLES REGARDING TREATMENT
RECOMMENDATIONS
The following treatment recommendations have been formulated to provide a
basis for discussion between the woman and her health-care provider about the use
of ZDV to reduce perinatal transmission. HIV-infected women should be informed of
the substantial benefit and short-term safety of ZDV administered during pregnancy
and the neonatal period observed in ACTG Protocol 076. However, they also must be
*FDA pregnancy categories are: A, in which adequate and well-controlled studies of pregnant
women fail to demonstrate a risk to the fetus during the first trimester of pregnancy (and there
is no evidence of a risk during later trimesters); B, in which animal reproduction studies fail
to demonstrate a risk to the fetus and adequate and well-controlled studies of pregnant women
have not been conducted; C, in which safety in human pregnancies has not been determined,
animal studies are either positive for fetal risk or have not been conducted, and the drug
should not be used unless the potential benefit outweighs the potential risk to the fetus; D, in
which there is positive evidence of human fetal risk based on adverse reaction data from
investigational or marketing experiences, but the potential benefits from the use of the drug
in pregnant women may be acceptable despite its potential risks; and X, in which studies in
animals or reports of adverse reactions have indicated that the risk associated with the use
of the drug for pregnant women clearly outweighs any possible benefit.