Zidovudine as an immunomodulatory agent

In view of the increase of HIV infection in women, and of transplacental infectivity, 3'-azido-3'-deoxythymidine (zidovudine) is being explored to control infection in offspring. Zidovudine toxicity in humans and experimental animals is well documented. However, information on immunotoxicity in pregnant females and their offspring is lacking. We exposed pregnant female mice to zidovudine to provide data, and perhaps baseline evaluation, on zidovudine immunotoxicity in primiparous females and their progeny. In pregnant mice exposed to zidovudine (0.2 mg/ml) in drinking water, enhancement of the mixed lymphocyte response (MLR) occurs; suppression is not seen until the 7th month. Profound, persistent suppression is seen in their progeny first detected at one week of age. Suppression in virgin females occurs 1 month after treatment, which persists through the seventh month. The antibody forming cell response is enhanced in primiparous females and their offspring, but is not affected in virgin females. After weekly alternation of oral treatment with two 0.5 ml intravenous injections at 0.2 mg/ml, MLR suppression occurs after 1 month in primiparous females, while in their progeny and in virgins enhancement is seen first; in progeny suppression is observed at 3 months. Thus, zidovudine is immunosuppressive for T-cell mediated immunity and the kind of modulation is a function of treatment regimen.