REDUCTION OF MATERNAL-INFANT TRANSMISSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 WITH ZIDOVUDINE TREATMENT

Background and Methods. Maternal-infant transmission is the primary me ans by which young children become infected with human immunodeficienc y virus type 1 (HIV). We conducted a randomized, double-blind, placebo -controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission. HIV-infected pregnant w omen (14 to 34 weeks' gestation) with CD4+ T-lymphocyte counts above 2 00 cells per cubic millimeter who had not received antiretroviral ther apy during the current pregnancy were enrolled. The zidovudine regimen included antepartum zidovudine (100 mg orally five times daily), intr apartum zidovudine (2 mg per kilogram of body weight given intravenous ly over a one-hour period, then 1 mg per kilogram per hour until deliv ery), and zidovudine for the newborn (2 mg per kilogram orally every s ix hours for six weeks). Infants with at least one positive HIV cultur e of peripheral-blood mononuclear cells were classified as HIV-infecte d. Results. From April 1991 through December 20, 1993, the cutoff date for the first interim analysis of efficacy, 477 pregnant women were e nrolled; during the study period, 409 gave birth to 415 live-born infa nts. HIV-infection status was known for 363 births (180 in the zidovud ine group and 183 in the placebo group). Thirteen infants in the zidov udine group and 40 in the placebo group were HIV-infected. The proport ions infected at 18 months, as estimated by the Kaplan-Meier method, w ere 8.3 percent (95 percent confidence interval, 3.9 to 12.8 percent) in the zidovudine group and 25.5 percent (95 percent confidence interv al, 18.4 to 32.5 percent) in the placebo group. This corresponds to a 67.5 percent (95 percent confidence interval, 40.7 to 82.1 percent) re lative reduction in the risk of HIV transmission (Z = 4.03, P = 0.0000 6). Minimal short-term toxic effects were observed. The level of hemog lobin at birth in the infants in the zidovudine group was significantl y lower than that in the infants in the placebo group. By 12 weeks of age, hemoglobin values in the two groups were similar. Conclusions. In pregnant women with mildly symptomatic HIV disease and no prior treat ment with antiretroviral drugs during the pregnancy, a regimen consist ing of zidovudine given ante partum and intra partum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two thirds.