Lamivudine-Zidovudine Combination for Prevention of Maternal-Infant Transmission of HIV-1

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Abstract
The efficacy of antiretroviral drugs to prevent maternal-infant transmission of human immunodeficiency virus 1 (HIV-1) was first demonstrated in 1994.1 As soon as these data were made public, zidovudine monotherapy prophylaxis became the standard of care; a similar two-thirds decline in transmission rates was reported in observational cohort studies.2,3 More recently, antiretroviral combinations have been used in pregnancy for maternal health.4,5 Combination therapies also have been considered increasingly as a means to further decrease risk of maternal-infant transmission. The combination most frequently used for this purpose since 1995 is lamivudine-zidovudine because it was shown to lower viral load and improve outcome in HIV-infected patients.6 In a phase 1/phase 2 trial,7 the pharmacokinetics of lamivudine were not modified by pregnancy, and placental blood concentrations were within the therapeutic range, suggesting passive placental transfer. We recently reported that lamivudine accumulates at 5-fold higher concentrations in amniotic fluid.8 There are now preliminary observational studies of lamivudine-zidovudine in pregnancy,9,10 as well as a large clinical trial that showed a decrease in maternal-infant transmission of up to 50% compared with placebo in a breastfeeding population in Africa.11

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