Reports on HIV/AIDS: 1990

JANUARY 26, 1990, MMWR, Vol. 39, RR-1: [inclusive page numbers]
safety of zidovudine use during pregnancy, the Burroughs-Wellcome Company has
developed a registry to evaluate pregnancy outcomes of women who took zidovudine
during pregnancy. Physicians are encouraged to register such persons by telephoning the pregnancy registry, [phone] (collect) or 1-800-722-9292. It is also not
known whether zidovudine is excreted in human milk. However, because of the
potential for adverse side effects among breast-fed infants, as well as the potential for
transmission of HIV if the mother is infected, mothers should be instructed to
discontinue breast-feeding whether or not they are receiving zidovudine (17).
In other studies conducted by the Burroughs-Wellcome Company (Appendix I),
vaginal tumors, including carcinomas, were observed in mice and rats receiving
zidovudine at doses that the FDA has determined resulted in plasma levels in mice
approximately equal to human plasma levels at the dose originally approved for
treatment of persons with symptomatic HIV infection (200 mg every 4 hours). In rats,
the plasma levels were determined by the FDA to be about 10 times higher than
human plasma levels achieved with the originally approved dose. The results of these
rodent carcinogenicity studies are of uncertain predictive value for humans.
Studies of Zidovudine Postexposure Prophylaxis Involving Animals
Data involving studies of laboratory animals (Appendix II) are limited and must be
interpreted with caution, as they have most often been derived by using nonhuman
retroviruses having pathogenic mechanisms different from the pathogenesis of HIV
infection in humans. In one study using HIV in a mouse model, zidovudine prophylaxis was begun 24 hours before intrathymic injection of a large inoculum of HIV and
continued for 2 weeks thereafter. HIV infection was not prevented in any of the
animals studied, although the course of infection was modified. It is not known
whether prophylaxis would be effective in conditions that more closely resemble
occupational exposures, i.e., zidovudine begun after exposure, with the exposure
consisting of a percutaneous injection of a lower inoculum of HIV. Data from animal
studies are inadequate to support or reject the hypothesis that zidovudine may be
effective prophylaxis for persons who have been occupationally exposed to HIV.
Studies of Zidovudine Postexposure Prophylaxis Involving Humans
The efficacy of zidovudine prophylaxis for humans after exposure to HIV cannot
be assessed because of insufficient data. The Burroughs-Wellcome Company recently sponsored a double-blind, placebo-controlled study to evaluate 6 weeks of
zidovudine prophylaxis (200 mg orally every 4 hours) involving health-care workers
who had experienced occupational percutaneous, mucous-membrane, or nonintactskin exposures to HIV-infected blood. Of 84 workers who initially enrolled in the study
(49 of whom were given zidovudine), none developed HIV infection after at least 6
months of follow-up. The risk of transmission of HIV per episode of percutaneous
exposure to HIV-infected blood is, on the average, approximately 0.4% (7). Thus, the
absence of seroconversions in this small group of participants is not unexpected,
regardless of whether they took zidovudine. Enrollment in this study was terminated
in June 1989.
NIAID has enrolled three persons in an ongoing open trial of zidovudine prophylaxis after a "massive exposure" to HIV. The first person received a blood transfusion
from an HIV-infected donor, was started on zidovudine 7 days after exposure, and

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