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

12

MMWR

August 5, 1994

Intrapartum ZDV cannot prevent the substantial number of infections that occur before labor (26). Therefore, ZDV administered only during labor and to the
newborn may not be effective.
Because the mother would receive ZDV only during labor, her risk for developing resistant virus or ZDV toxicity would be minimal. The primary risk is that
associated with an intravenous catheter. The risk to the infant would be limited
to the potential toxicity associated with transfer of drug from the maternal intrapartum infusion and with 6 weeks of oral ZDV therapy, without in utero exposure
to the drug. The effect of neonatal ZDV treatment in ameliorating disease progression in infected infants is unknown. Clinical trials should be designed to
address the efficacy of antiretroviral therapy in this situation.
Recommendation:
For women with HIV infection who are in labor and who have not received the
antepartum component of the ACTG Protocol 076 regimen (either because of
lack of prenatal care or because they did not wish to receive antepartum therapy), the health-care provider should discuss the benefits and potential risks of
the intrapartum and neonatal components of the ACTG Protocol 076 regimen
and offer ZDV therapy when the clinical situation permits.
VI. Infants who are born to HIV-infected women who have received no intrapartum
ZDV therapy.
Discussion:
Infants whose mothers have not received ZDV during late pregnancy and/or
labor will not have circulating ZDV levels during birth, a period of presumed viral
exposure. Data are insufficient to allow assessment of the potential efficacy of
postexposure prophylaxis with ZDV in this situation. Studies of postexposure
prophylaxis of retroviral infection with ZDV in animal models have yielded
inconclusive results. Additionally, studies involving animal models should be
interpreted with caution: many of these studies have involved nonhuman
retroviruses that may have different pathogenic mechanisms from those of HIV,
used methods of viral inoculation that are not relevant to perinatal transmission
(e.g., intrathymic injection), and/or used a massive inoculum of virus (47).
The limited data from animal studies indicate that if ZDV is to have any effect
as postexposure prophylaxis, prompt administration (within hours) is important, and that even with early initiation of ZDV, such prophylaxis may not be
protective. In a SCID-hu mouse model of HIV infection (an immune-deficient
model reconstituted with human cells), a time-dependent suppression of HIV
replication was observed with ZDV prophylaxis (48). When ZDV was administered within 2 hours of viral inoculation, viral replication was not detectable at 2
weeks after inoculation in all treated animals; when ZDV was administered 2-36
hours after inoculation, rates of viral detection at 2 weeks increased in proportion to increasing time since ZDV was administered; and when ZDV was
administered 48 hours after inoculation, virus was detectable in all animals (48).
Therefore, whether the effect of ZDV therapy is prevention or suppression of
infection cannot be established. In several animal model systems, ZDV administration was observed only to suppress or ameliorate retroviral infection (49-51).