A trial of shortened zidovudine regimens to prevent mother-to-child transmission of human immunodeficiency virus type 1

Background: The optimal duration of zidovudine administration to prevent pe rinatal transmission of human immunodeficiency virus type 1 (HIV-1) should be determined to facilitate its use in areas where resources are limited. Methods: We conducted a randomized, double-blind equivalence trial of four regimens of zidovudine starting in the mother at 28 weeks' gestation, with 6 weeks of treatment in the infant (the long-long regimen), which is simila r to protocol 076; zidovudine starting at 35 weeks' gestation, with 3 days of treatment in the infant (the short-short regimen); a long-short regimen; and a short-long regimen. The mothers received zidovudine orally during la bor. The infants were fed formula and were tested for HIV DNA at 1, 45, 120 , and 180 days. After the first interim analysis, the short-short regimen w as stopped. Results: A total of 1437 women were enrolled. At the first interim analysis , the rates of HIV transmission were 4.1 percent for the long-long regimen and 10.5 percent for the short-short regimen (P=0.004); at this point the s hort-short regimen was stopped. For the entire study period, the transmissi on rates were 6.5 percent (95 percent confidence interval, 4.1 to 8.9 perce nt) for the long-long regimen, 4.7 percent (95 percent confidence interval, 2.4 to 7.0 percent) for the long-short regimen, and 8.6 percent (95 percen t confidence interval, 5.6 to 11.6 percent) for the short-long regimen. The rate of in utero transmission was significantly higher with the two regime ns with shorter maternal treatment (5.1 percent) than with the two with lon ger maternal treatment (1.6 percent). Conclusions: The short-short zidovudine regimen is inferior to the long-lon g regimen and leads to a higher rate of perinatal HIV transmission. The lon g-short, short-long, and long-long regimens had equivalent efficacy. Howeve r, the higher rate of in utero transmission with the short-long regimen sug gests that longer treatment of the infant cannot substitute for longer trea tment of the mother. (N Engl J Med 2000;343:982-91.) (C) 2000, Massachusett s Medical Society.