Background: The HIV paediatric epidemic in Africa is still growing mainly for operational reasons of lack of access to prevention of mother-to-child intervention programs (PMTCT). Up to date, several arguments are in favour of the early and systematic initiation of antiretroviral treatment among HIV-infected children aged less than 6-months to improve their survival, irrespectively of their symptomatology. To improve the access to paediatric antiretroviral roll-out in low-income countries, it is crucial to assess public health strategies of early HIV diagnosis and life-long HIV care including systematic antiretroviral therapy targeted on HIV-infected children less than 12 months. This early initiation of antiretroviral treatement in infant raises questions about their long-term effects in terms of safety, efficacy, compliance, resistance. As simplification of successful antiretroviral treatment is being assessed among adults, it is currently a relevant question to assess these life-course treatments in African children. This project is aimed to assess the feasability of simplication of a successful therapy using a once-daily triple therapy instead of a twice-daily treatment to preserv long-term compliance. The MONOD project is mainly based on an international randomised phase 2b trial that will study a once-a-day maintenance strategy after a 15-month induction antiretroviral therapy among HIV-infected children diagnosed early between age 6 and 52 weeks and in virologic success in three African research clinical sites: Abidjan, Côte d’Ivoire, Kigali, Rwanda, and Ouagadougou, Burkina Faso. Trial design: international open label phase 2b randomised controlled-trial, conducted over two consecutive steps: Step 1: prospective treatment cohort study: induction phase with twice-daily treatment during 15 months of all children from six weeks of life under triple therapy (AZT-3TC-NVP or AZT-3TC-LPV/r if previously exposed to PMTCT) together with Cotrimoxazole prophylaxis and education regarding treatment.Step 2: Phase 2b trial of the maintenance triple therapy for 12 months. Those children in virological success at the end of phase 1 (HIV-ARN <50 copies/mL on two consecutive samples at three months interval) will be randomised in three arms: two once-daily strategies: ABC-3TC-EFV or TDF-FTC-EFV and the continuation of the twice-daily induction arm as a comparison strategy. Sample size: initial prospective cohort (N=210), then phase 2b trial (n=(2*50)+(2*40)=180)Main endpoint: efficacy measured by survival without virological failure 12 months after initiation of maintenance treatment. Expected outcome: This trial aims at identifying simplified antiretroviral treatments strategies to be given once daily in children infected with HIV from the age of 15 months (from 6 kg) in real field conditions of use in Africa. It will improve the antiretroviral roll-out in children, with a specific focus on long-term strategies adapted to resource-limited settings.