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

• Published in: JAMA : the journal of the American Medical Association Vol. 285; no. 16; pp. 2083 - 2093
• Main Authors: Mandelbrot, Laurent, Landreau-Mascaro, Aline, Rekacewicz, Claire, Berrebi, Alain, Bénifla, Jean Louis, Burgard, Marianne, Lachassine, Eric, Barret, Béatrice, Chaix, Marie-Laure, Bongain, André, Ciraru-Vigneron, Nicole, Crenn-Hébert, Catherine, Delfraissy, Jean-François, Rouzioux, Christine, Mayaux, Marie-Jeanne, Blanche, Stéphane, for the Agence Nationale de Recherches sur le SIDA (ANRS) 075 Study Group
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 25.04.2001
• Subjects: Anti-HIV Agents - therapeutic use; Babies; Biological and medical sciences; Clinical trials; Drug resistance; Drug Resistance, Microbial; Drug therapy; Drug Therapy, Combination; Female; HIV; HIV Infections - drug therapy; HIV Infections - prevention & control; HIV Infections - transmission; HIV-1 - drug effects; HIV-1 - genetics; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical - prevention & control; Infectious diseases; Lamivudine - therapeutic use; Medical sciences; Mothers; Multivariate Analysis; Pregnancy; Pregnancy Complications, Infectious - drug therapy; Preventive medicine; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Zidovudine - therapeutic use; RNA-directed DNA polymerase; Prevention; Cohort study; Antiviral; Child; Pyrimidine nucleoside; Human; Immunopathology; Drug combination; Enzyme; Transferases; Enzyme inhibitor; Retroviridae; Lamivudine; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Nucleotidyltransferases; Chemotherapy; Viral disease; Dideoxynucleoside; Vertical transmission; Human immunodeficiency virus; Zidovudine
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.285.16.2083

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.