Rapid development of genotypic resistance to lamivudine when combined withzidovudine in pregnancy

The prevention of mother to child transmission of HIV-1 by zidovudine monot herapy is well known, but increasingly combination anti-retroviral therapy is prescribed during pregnancy. In this prospective study, 19 pregnant wome n with human immunodeficiency virus-1 (HIV-1) infection who elected to take antiretroviral therapy during the second and third trimesters were treated with zidovudine or zidovudine plus lamivudine. Fourteen women treated with zidovudine monotherapy had a mean 0.3 log(10) reduction in viral load and a mean 52 x 10(6)/L (17%) increase in CD4+ lymphocytes at delivery compared with pre-treatment samples. Genotypic mutations associated with decreased susceptibility to zidovudine were detected in 2 of 10 women at delivery. Fi ve women with more advanced HIV-1 infection were treated with zidovudine pl us lamivudine and a mean 1.5 log(10) reduction in viral load together with a mean 30 x 10(6)/L (33%) increase in CD4+ lymphocytes was observed in this group. However, four of five women in the dual therapy arm had the M184V m utation in the reverse transcriptase gene associated with decreased suscept ibility to lamivudine at delivery. We conclude that zidovudine plus lamivud ine reduced HIV-1 plasma viraemia to low levels in pregnant women with adva nced HIV-1 disease but the rapid development of genotypic resistance to lam ivudine indicates that additional therapy is required both for the long-ter m benefit of the mothers and to prevent the development of resistant virus that may be transmitted to the infant. (C) 1999 Wiley-Liss, Inc.