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

Vol. 43 / No. RR-11

MMWR

11

who are receiving alternative antiretroviral agents because of disease progression has not been defined.
The capability of ZDV to reduce HIV transmission may be decreased for mothers in whom ZDV-resistant strains predominate, particularly if the strains have
high-level resistance; however, this assumption is not yet supported by data.
Further clinical trials to evaluate alternative approaches for such women are
needed.
Recommendation:
Because data are insufficient to extrapolate the potential efficacy of the ACTG
Protocol 076 regimen for this population of women, the health-care provider
should consider recommending the ACTG Protocol 076 regimen on a case-bycase basis after a discussion of the risks and benefits with the pregnant woman.
Issues to be discussed include her clinical and immunologic stability on ZDV
therapy, the likelihood that she is infected with a ZDV-resistant HIV strain, and, if
relevant, the reasons for her current use of an alternative antiretroviral agent
(e.g., lack of response to or intolerance of ZDV therapy). Consultation with experts in HIV infection may be warranted. The health-care provider should make
the ACTG Protocol 076 regimen available to the woman, although its effectiveness may vary depending on her clinical status.
V. Pregnant HIV-infected women who have not received antepartum antiretroviral
therapy and who are in labor.
Discussion:
Data from studies in humans are insufficient to evaluate the potential effectiveness of ZDV in this situation. Because the mother's exposure to ZDV would
be brief, such therapy can be expected to have no effect on the level of maternal
virus in blood or genital secretions. However, because of the intravenous loading dose and continuous infusion of ZDV during labor, the infant will be born
with circulating levels of ZDV similar to those of infants whose mothers have
received antenatal as well as intrapartum ZDV. ZDV may have some utility for
this group of patients-regardless of whether the pregnancy is at term or preterm-because the presence of systemic levels of ZDV in the infant before or
shortly after HIV exposure through contact with the mother's blood and genital
secretions during delivery may help prevent intrapartum transmission.
The intravenous route was chosen for drug dosing during labor in ACTG Protocol 076 because continuous intravenous infusion of drug after an initial
loading dose results in predictable levels of ZDV in the mother. Under optimal
circumstances, these maternal levels provide a substantial fetal blood level during birth, when the infant is presumed to be exposed extensively to HIV through
contact with the mother's blood and genital secretions. Because gastric emptying is delayed during labor, the absorption of orally administered drugs is
unpredictable (46). Therefore, oral administration of ZDV during labor might
produce widely variable systemic levels in the mother and infant. Oral ZDV administered intrapartum cannot be assumed to be equivalent to the intravenous
intrapartum ZDV component used in ACTG Protocol 076. Further studies are
needed to characterize the pharmacokinetics of oral ZDV during labor.