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

Serial sonographic evaluations for fetal growth and amniotic fluid volume as conducted in the study (at entry and every 4 weeks from 28 weeks of gestation until
delivery) demonstrated no differences between pregnancies in women who had
received placebo or ZDV. Birth parameters (gestational age; birth weight, length, and
head circumference; and Apgar scores) were similar among infants born to women in
either group. The median birth weight was 3,160 g (range: 1,040-5,267 g), and the
median gestational age at birth was 39 weeks (range: 27-43 weeks). No statistically
significant difference was observed between the ZDV and placebo groups in the number of infants with birth weight <2,500 g, who were small or large for gestational age,
or who were born prematurely. The occurrence of major or minor congenital abnormalities was approximately equal between the two groups, and no pattern in the type
of abnormalities was observed.
The infants in the study tolerated the ZDV therapy well. The only adverse effect
observed more frequently among infants in the ZDV treatment group was mild, transient anemia. Hemoglobin values for infants in the group receiving ZDV were lower
than for the group receiving placebo, with a maximum mean difference of 1 gm/dL
occurring at 3 weeks of age. The lowest mean hemoglobin value in infants receiving
ZDV occurred at 6 weeks of age and resolved without therapy for anemia after the
infants had completed the ZDV treatment. The hemoglobin values of infants receiving
ZDV were similar to those of placebo recipients by 12 weeks of age. The incidence of
neutropenia and serum chemistry abnormalities was similar between ZDV and placebo groups of infants, and no difference in the pattern of chemistry abnormalities
was observed.
Based on these interim findings, NIAID accepted the recommendation of its independent data and safety monitoring board to terminate enrollment into the trial and to
offer ZDV to women in the placebo group who had not yet delivered and to their
infants up to 6 weeks of age.* Follow-up of patients enrolled in the study is ongoing.
Limitations in Interpretation and Extrapolation of ACTG Protocol 076
Results
This clinical trial demonstrated that the ACTG Protocol 076 ZDV regimen can substantially reduce perinatal HIV transmission. However, several important limitations
should be noted. First, perinatal HIV transmission was still observed despite drug therapy. Second, the efficacy of this therapy is unknown for HIV-infected pregnant women
who have advanced disease, who have received prior antiretroviral therapy, or who
have ZDV-resistant virus strains. Third, although the ZDV regimen used in this trial
was not associated with serious short-term adverse effects, such effects may be
observed when this use of ZDV becomes more widespread. Fourth, the long-term
risks for the child associated with exposure to ZDV in utero and early infancy have not
been determined. Fifth, it is not known if use of ZDV during pregnancy will affect the
drug's efficacy for the woman when it becomes clinically indicated for her own health.
Further complicating the incorporation of this ZDV regimen into clinical practice is
the fact that some HIV-infected women seek medical care late in pregnancy or when
*A summary of the study's findings is available from the AIDS Clinical Trials Information Service
at 1(800)TRIALS-A (1[8001874-2572).