Lamivudine-Zidovudine Combination for Prevention of Maternal-Infant Transmission of HIV-1
- Laurent Mandelbrot, MD;
- Aline Landreau-Mascaro, MS;
- Claire Rekacewicz, MD;
- Alain Berrebi, MD;
- Jean Louis Bénifla, MD;
- Marianne Burgard, PhD;
- Eric Lachassine, MD;
- Béatrice Barret, MD;
- Marie-Laure Chaix, PhD;
- André Bongain, MD;
- Nicole Ciraru-Vigneron, MD;
- Catherine Crenn-Hébert, MD;
- Jean-François Delfraissy, MD;
- Christine Rouzioux, PhD;
- Marie-Jeanne Mayaux, BA;
- Stéphane Blanche, MD;
- for the Agence Nationale de Recherches sur le SIDA (ANRS) 075 Study Group
- Author Affiliations: Department of Obstetrics-Gynecology, Hôpital Cochin (Dr Mandelbrot), Department of Obstetrics-Gynecology, Hôpital Bichat (Dr Bénifla), Departments of Virology (Drs Burgard, Chaix, and Rouzioux) and Pediatric Immunology (Dr Blanche), Hôpital Necker, and Department of Obstetrics-Gynecology, Hôpital Lariboisière (Dr Ciraru-Vigneron), Paris, France; Institut National de la Santé et de la Recherche Médicale Unité 292 (Mss Landreau-Mascaro and Mayaux and Drs Rekacewicz and Barret) and Department of Internal Medicine, Hôpital Kremlin-Bicêtre (Dr Delfraissy), Kremlin-Bicêtre, France; Department of Obstetrics-Gynecology, Hôpital La Grave, Toulouse, France (Dr Berrebi); Department of Obstetrics-Gynecology, Hôpital Jean Verdier, Bondy, France (Dr Lachassine); Department of Obstetrics-Gynecology, Hôpital l'Archet 2, Nice, France (Dr Bongain); and Department of Obstetrics-Gynecology, Hôpital Louis Mourier, Colombes, France (Dr Crenn-Hébert).
Abstract
Context Zidovudine reduces maternal-infant transmission of human immunodeficiency virus 1 (HIV-1) infection by two thirds. Combination antiretroviral therapies are potentially more effective prevention.
Objectives To assess the safety of perinatal lamivudine-zidovudine therapy, especially in children, and its effects on viral load, acquisition of drug resistance, and maternal-infant transmission of HIV-1 in a nonbreastfeeding population.
Design and Setting The Agence Nationale de Recherches sur le SIDA (ANRS) 075 Study, an open-label, nonrandomized intervention trial conducted in the context of an ongoing observational cohort study in 48 sites in France.
Patients A total of 445 HIV-1–infected pregnant women were enrolled as the study cohort from February 1997 to September 1998; controls consisted of 899 pregnant women who had received zidovudine monotherapy in May 1994 to February 1997 as standard care.
Intervention The study cohort received lamivudine in addition to the standard Pediatric AIDS Clinical Trial Group 076 Study zidovudine prophylaxis regimen. Lamivudine was initiated in women at 32 weeks' gestation through delivery at 150 mg twice per day orally; children received lamivudine, 2 mg/kg twice per day for 6 weeks.
Main Outcome Measures HIV-1 infection status and tolerance of therapy in children through age 18 months; maternal plasma HIV-1 RNA levels through 6 weeks after delivery.
Results The transmission rate in the study group was 1.6% (7/437; 95% confidence interval [CI], 0.7%-3.3%). In a multivariable analysis, transmission in the study group was 5-fold lower than in controls. In the study group, maternal plasma HIV-1 RNA level was less than 500 copies/mL at delivery in 74%; the median decrease was 1.24 (range, −1.63 to 3.40) log10 copies/mL. The M184V lamivudine resistance mutation was detected at 6 weeks after delivery in specimens from 52 of 132 women. The most frequent serious adverse events in children were neutropenia and anemia, requiring blood transfusion in 9 children and premature treatment discontinuation in 19. Two uninfected children died at age 1 year from neurologic complications related to mitochondrial dysfunction.
Conclusions Lamivudine-zidovudine may be effective in preventing maternal-infant HIV transmission. However, severe adverse effects and emergence of resistance to lamivudine occurred. Thus, the role of this combination therapy in this setting is as yet unclear, and further research involving a variety of strategies is needed to definitively ascertain its utility for preventing maternal-infant HIV transmission.
