AZT in pregnancy

AZT (zidovudine, Retrovir) was the first antiretroviral drug to be used in pregnant women with HIV and remains the best studied. According to many guidelines, it remains a viable treatment option for women with low viral loads who do not yet want to take combination therapy. It is also a commonly used treatment to prevent mother-to-child transmission in resource-limited settings.

The placebo-controlled ACTG 076 trial proved that AZT use could reduce mother-to-baby transmission of HIV among pregnant women with CD4 cell counts above 200 cells/mm3 who had not previously taken AZT.1 The AZT arm had three components:

  • AZT was given to pregnant women by mouth starting between weeks 14 and 34 at a dose of 100mg five times a day.
  • During labour, women were treated with intravenous AZT.
  • After birth, AZT syrup was given to the infants for the first six weeks of life.

Only 8% of the women randomised to AZT transmitted HIV to their babies compared to 26% among those on placebo.

A subsequent observational study of 939 infants born to HIV-positive mothers in New York confirmed the need for all three components of AZT treatment. When AZT was started in the prenatal period, the transmission rate was 6% but there was a 10% transmission rate among babies born to women who began AZT only during delivery. Similarly, the course of AZT given to the newborn was found to be necessary for maximal reductions in transmission.2

AZT probably reduces transmission by lowering maternal viral load (although by only 0.3 log10 in ACTG 076), and by working as post-exposure prophylaxis in the newborn.3

The ACTG 076 trial had a very significant impact on mother-to-baby transmission in countries where its use was widely adopted. For example, in France there has been a two-thirds reduction in mother-to-baby transmission since the adoption of a policy of offering maternal AZT treatment in 1994. Similarly, in the United States, mother-to-baby transmission peaked in 1992 and fell by 67% five years later. Over the same period, the proportion of women taking AZT to prevent transmission rose from 7 to 91%.4

References

  1. Connor EM et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. N Engl J Med 331: 1173-1180, 1994
  2. Wade NA et al. Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human immunodeficiency virus. N Engl J Med 339: 20, 1409, 1998
  3. Mofenson L et al. Risk factors for perinatal transmission of HIV type 1 in women treated with zidovudine. N Engl J Med 341: 385-393, 1999
  4. Lindgren ML et al. Trends in perinatal transmission of HIV/AIDS in the United States. JAMA 282: 531, 1999
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