PROMISE-PEP / ANRS 12174
The randomised controlled clinical trial, conducted in Burkina Faso, South Africa, Uganda and Zambia, compared two prophylactic treatment regimens to prevent transmission of HIV from mother to child during 12 months of breastfeeding. It compared the efficacy of infant lopinavir/ritonavir (LPV/r, 40/10mg twice daily if 2-4kg and 80/20mg twice daily if >4kg) versus lamivudine 7,5mg twice daily if 2-4kg, 25mg twice daily if 4-8kg and 50mg twice daily if >8kg) from day 7 until 4 weeks after cessation of breastfeeding (maximum duration of prophylaxis: 50 weeks for a recommended maximum duration of breastfeeding of 49 weeks) in preventing postnatal HIV-1 acquisition between 7 days and 50 weeks of age.
Between November 2009, and May 2012, 1273 infants were enrolled and 1236 were analysed; 615 assigned to lopinavir–ritonavir and 621 assigned to lamivudine. The HIV-infected mothers involved were not receiving ARV therapy after giving birth as per WHO guidelines at the time of recruitment. A total of 17 HIV infections were diagnosed in the study period resulting in cumulative HIV-1 infection of 1•4% and 1•5%, respectively. Infection rates did not differ between the two drug regimens.
Half of the postnatal HIV-1 infections in both groups occurred after 6 months of breastfeeding. Further analysis of the data suggested that most of the HIV infections in both groups occurred because of lack of adherence to the study drug. The authors conclude that this finding “justifies the extension of infant pre-exposure prophylaxis (PrEP) until the end of HIV exposure and the need to inform mothers about the persistent risk of transmission throughout breastfeeding to prevent them stopping giving the treatment to their babies too soon.” “Drug adherence therefore remains a key factor for success of infant PrEP. More research is needed for more palatable oral paediatric formulations and long-acting injectable drugs.”