Abstract
BackgroundPostnatal transmission of HIV-1 through breast milk remains an unsolved challenge in many resource-poor settings where replacement feeding is not a safe alternative. WHO now recommends breastfeeding of infants born to HIV-infected mothers until 12 months of age, with either maternal highly active antiretroviral therapy (HAART) or peri-exposure prophylaxis (PEP) in infants using nevirapine. As PEP, lamivudine showed a similar efficacy and safety as nevirapine, but with an expected lower rate of resistant HIV strains emerging in infants who fail PEP, and lower restrictions for future HIV treatment. Lopinavir/ritonavir (LPV/r) is an attractive PEP candidate with presumably higher efficacy against HIV than nevirapine or lamivudine, and a higher genetic barrier to resistance selection. It showed an acceptable safety profile for the treatment of very young HIV-infected infants. The ANRS 12174 study aims to compare the risk of HIV-1 transmission during and safety of prolonged infant PEP with LPV/r (40/10 mg twice daily if 2-4 kg and 80/20 mg twice daily if >4 kg) versus Lamivudine (7,5 mg twice daily if 2-4 kg, 25 mg twice daily if 4-8 kg and 50 mg twice daily if >8 kg) from day 7 until one week after cessation of BF (maximum 50 weeks of prophylaxis) to prevent postnatal HIV-1 acquisition between 7 days and 50 weeks of age.MethodsThe ANRS 12174 study is a multinational, randomised controlled clinical trial conducted on 1,500 mother-infant pairs in Burkina Faso, South Africa, Uganda and Zambia. We will recommend exclusive breastfeeding (EBF) until 26th week of life and cessation of breastfeeding at a maximum of 49 weeks in both trial arms.HIV-uninfected infants at day 7 (± 2 days) born to HIV-1 infected mothers not eligible for HAART who choose to breastfeed their infants.The primary endpoint is the acquisition of HIV-1 (as assessed by HIV-1 DNA PCR) between day 7 and 50 weeks of age. Secondary endpoints are safety (including resistance, adverse events and growth) until 50 weeks and HIV-1-free survival until 50 weeks.DiscussionThis study will provide a new evidence-based intervention to support HIV-1-infected women not eligible for HAART to safely breastfeed their babies.Trial registration number ( http://www.clinicaltrials.gov)NCT00640263
Highlights
Postnatal transmission of HIV-1 through breast milk remains an unsolved challenge in many resource-poor settings
NVP was studied more extensively than Lamivudine for peri-exposure prophylaxis (PEP) purposes, we decided to use the latter drug for the comparative arm as we expect a similar efficacy as NVP with similar adverse events but with less detrimental genetic barrier profile
We believe that the ‘cost’ of using NVP for PEP during breastfeeding is too high to recommend this drug for prevention of postnatal HIV transmission
Summary
Postnatal transmission of HIV-1 through breast milk remains an unsolved challenge in many resource-poor settings where replacement feeding is not a safe alternative. Lopinavir/ritonavir (LPV/r) is an attractive PEP candidate with presumably higher efficacy against HIV than nevirapine or lamivudine, and a higher genetic barrier to resistance selection It showed an acceptable safety profile for the treatment of very young HIV-infected infants. Exclusively or predominantly breastfed infants are likely to have a substantially lower risk of succumbing to common childhood infections such as diarrhoea and pneumonia [7,8] that inflict a substantial nutritional insult. Strategies that both prevent MTCT and allow for optimal breastfeeding are urgently needed. Another study in Botswana reported even lower transmission risks at 6 months using two different HAART regimens (2% and 1%) [10]
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