Triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV-1 (Kesho Bora study): a randomised controlled trial

• Published in: The Lancet infectious diseases 2011-03, Vol.11 (3), p.171-180
• Main Author: de Vincenzi, Isabelle
• Format: Article
• Language: English
• Subjects: Adult; Africa South of the Sahara - epidemiology; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral agents; Antiviral agents; Biological and medical sciences; Breast Feeding; CD4 Lymphocyte Count; Drug Therapy, Combination; Female; HIV Infections - drug therapy; HIV Infections - epidemiology; HIV Infections - transmission; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infant; Infant, Newborn; Infectious Disease; Infectious Disease Transmission, Vertical - prevention & control; Infectious diseases; Medical sciences; Nevirapine - administration & dosage; Nevirapine - therapeutic use; Pharmacology. Drug treatments; Pregnancy; Pregnancy Complications, Infectious - drug therapy; Prophylaxis; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Young Adult; Zidovudine - therapeutic use
• ISSN: 1473-3099; 1474-4457
• DOI: 10.1016/S1473-3099(10)70288-7

Summary Background Breastfeeding is essential for child health and development in low-resource settings but carries a significant risk of transmission of HIV-1, especially in late stages of maternal disease. We aimed to assess the efficacy and safety of triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis in pregnant women infected with HIV. Methods Pregnant women with WHO stage 1, 2, or 3 HIV-1 infection who had CD4 cell counts of 200–500 cells per μL were enrolled at five study sites in Burkina Faso, Kenya, and South Africa to start study treatment at 28–36 weeks' gestation. Women were randomly assigned (1:1) by a computer generated random sequence to either triple antiretroviral prophylaxis (a combination of 300 mg zidovudine, 150 mg lamivudine, and 400 mg lopinavir plus 100 mg ritonavir twice daily until cessation of breastfeeding to a maximum of 6·5 months post partum) or zidovudine and single-dose nevirapine (300 mg zidovudine twice daily until delivery and a dose of 600 mg zidovudine plus 200 mg nevirapine at the onset of labour and, after a protocol amendment in December, 2006, 1 week post-partum zidovudine 300 mg twice daily and lamivudine 150 mg twice daily). All infants received a 0·6 mL dose of nevirapine at birth and, from December, 2006, 4 mg/kg twice daily of zidovudine for 1 week after birth. Patients and investigators were not masked to treatment. The primary endpoints were HIV-free infant survival at 6 weeks and 12 months; HIV-free survival at 12 months in infants who were ever breastfed; AIDS-free survival in mothers at 18 months; and serious adverse events in mothers and babies. Analysis was by intention to treat. This trial is registered with Current Controlled Trials , ISRCTN71468401. Findings From June, 2005, to August, 2008, 882 women were enrolled, 824 of whom were randomised and gave birth to 805 singleton or first, liveborn infants. The cumulative rate of HIV transmission at 6 weeks was 3·3% (95% CI 1·9–5·6%) in the triple antiretroviral group compared with 5·0% (3·3–7·7%) in the zidovudine and single-dose nevirapine group, and at 12 months was 5·4% (3·6–8·1%) in the triple antiretroviral group compared with 9·5% (7·0–12·9%) in the zidovudine and single-dose nevirapine group (p=0·029). The cumulative rate of HIV transmission or death at 12 months was 10·2% (95% CI 7·6–13·6%) in the triple antiretroviral group compared with 16·0% (12·7–20·0%) in the zidovudine and single-dose nevirapine group (p=0·