Reports on HIV/AIDS: 1990

JANUARY 26, 1990, MMWR, Vol. 39, RR-1: [inclusive page numbers]
APPENDIX II
Studies of Zidovudine Prophylaxis Involving Animals
Studies of retrovirus infections other than HIV in mice and cats suggest that
zidovudine may alter the course of some retroviral infections when given before or
shortly after exposure to the virus. In one study, mice were injected with a large
challenge inoculum (1 X 104 plaque-forming units) of Rauscher murine leukemia virus
(RMLV) and were given a 20-day course of zidovudine, at various doses, beginning 4
hours after inoculation. By day 69, all untreated mice had died of RMLV infection,
whereas those treated with high doses of zidovudine had no clinical signs of infection
and were not viremic. Both the protective effect of zidovudine and the incidence of
zidovudine-induced bone marrow depression were greater with increasing doses (1).
In another study, cats were injected with a large challenge dose (2 X 103
focus-inducing units) of Rickard feline leukemia virus (RFLV) and were given zidovudine at various doses and various intervals after inoculation. Of eight cats injected
with RFLV and treated with a 6-week course of zidovudine beginning 1 hour after
inoculation, none developed clinical evidence of RFLV disease, none had virus
isolated from serum, and one had evidence of infection manifested by the development of neutralizing antibody within 3 months after treatment with zidovudine was
stopped. In contrast, 11 of 12 untreated cats either became viremic or died of infection
in the same period. When zidovudine prophylaxis was initiated 3 or 7 days after
inoculation, a substantial proportion of animals in different dosage groups became
viremic, developed neutralizing antibody, or both. All animals treated beginning 28
days after inoculation were viremic when zidovudine treatment was initiated (2).
Limited studies involving primates have not shown success in postexposure
prophylaxis against simian immunodeficiency virus (SIV). In one study, macaque
monkeys were inoculated with a small dose (10 TCIDso) of a rapidly lethal variant of
SIV (SMM/PBj-14) and later treated with zidovudine for 14 days. Of three animals
whose treatment was begun 1 hour after inoculation, two developed infection, and
one died. Of three animals treated within 24 hours, all developed infection, and two
died. Of three animals treated within 72 hours, all developed infection, and two died.
Of three control animals that were inoculated with the virus but not given zidovudine
treatment, all developed infection, and two died (3). In another study of macaque
monkeys, a 1-week course of zidovudine begun 8 hours before the animals were
inoculated with SIV did not prevent viremia, but delayed its onset until 1-2 days after
the zidovudine treatment was completed (4).
Finally, studies have been conducted by using the SCID-hu mouse model, an
immunodeficient mouse with an immune system that has been reconstituted with
transplanted human hematolymphoid organs susceptible to infection with HIV (5).
Seventeen mice were treated with zidovudine for 24 hours before and for 2 weeks
after intrathymic injection of a standard challenge dose of HIV (400-4,000 IU), the
smallest dose causing infection in all animals. At 2 weeks after injection, none of the
mice tested positive for HIV DNA by the polymerase chain reaction (PCR), although
the presence of HIV RNA in some cells was detected by in situ hybridization. Four
weeks after zidovudine was stopped, HIV DNA was detected by PCR in all 17 mice.
In comparison, all of 40 mice not receiving zidovudine tested positive for HIV DNA by
PCR 2 weeks after injection (6).

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