Purpose of the Study. Zidovudine (AZT) has been shown to reduce maternal-infant transmission of human immunodeficiency virus (HIV) by two thirds. Combination antiretroviral therapy may improve this transmission rate. The objectives of this study were to assess the safety of the combination of lamivudine (3TC)-AZT therapy for the prevention of maternal-infant HIV transmission.
Methods. An open label, nonrandomized trial was conducted at 48 clinical sites in France. Four-hundred forty-five HIV-infected pregnant women were enrolled in the study. The study cohort received 3TC in addition to standard AZT prophylaxis. The 3TC was initiated in women at 32 weeks’ gestation and given through delivery at 150 mg twice daily. Children born to these women received 3TC in addition to their AZT twice daily for 6 weeks after birth. Retrospective controls included 889 pregnant women who had received standard AZT monotherapy.
Results. The transmission rate in the study group was 1.6%. In a multi-variable analysis, this transmission rate was fivefold lower than in the control groups. The 3TC resistance mutation was detected 6 weeks after delivery in 52 of 132 women. The most frequent serious adverse events in the children included neutropenia and anemia, requiring blood transfusions in 9 children and premature treatment discontinuation in 19. Two uninfected infants died at 1 year of age from neurologic complications suggestive of mitochondrial dysfunction.
Conclusions. AZT-3TC appears to be effective in reducing maternal-infant HIV transmission. However, serious adverse events and the emergence of resistance to 3TC occurred.
Reviewer’s Comments. The safety and toxicity data presented by this study emphasize the need for close monitoring of women and children treated with combination antiretroviral therapy. Particular attention must be paid to the potential for hematologic and hepatologic toxicity in the infants born to women treated with combination therapy. The occurrence of mitochondrial dysfunction-related neurological complications, although not confirmed in retrospective US studies, emphasize the need for long-term follow up of children treated with perinatal antiretroviral combination therapy. Finally, the use of a 2-drug regimen in any individual must be considered less than optimal therapy. The rapid emergence of 3TC resistance in 40% of the women studied is of great concern. In the United States, the current practice is to treat pregnant women with highly active antiretroviral combinations that minimize her viral levels in the blood. This will substantially reduce the degree of maternal-infant transmission of HIV, but ongoing monitoring for toxicity to the fetus/infant is critical.
- Copyright © 2002 by the American Academy of Pediatrics