Between 2011 and 2013, global and national guidelines for preventing mother-to-child transmission (PMTCT) of HIV shifted to recommend Option B+, the provision of lifelong antiretroviral treatment for all HIV-infected pregnant women.We aimed to analyse how Option B+ reached the policy agenda, and unpack the processes, actors and politics that explain its adoption, with a focus on examining UNICEF's contribution to these events. Analysis drew on published articles and other documentation, 30 key informants interviews with staff at UNICEF, partner organisations and government officials, and country case studies. Cameroon, India, South Africa and Zimbabwe were each visited for 5-8 days. Interview transcripts were analysed using Dedoose software, reviewed several times and then coded thematically.A national policy initiative in Malawi in 2011, in which the country adopted Option B+, rather than existing WHO recommended regimens, irrevocably placed the policy on the global agenda. UNICEF and other organisations recognised the policy's potential impact and strategically crafted arguments to support it, framing these around operational considerations, cost-effectiveness and values. As 'policy entrepreneurs', these organisations vigorously promoted the policy through a variety of channels and means, overcoming concerted opposition. WHO, on the basis of scanty evidence, released a series of documents towards the policy's endorsement, paving the way for its widespread adoption. National-level policy transformation was rapid and definitive, distinct from previous incremental policy processes. Many organisations, including UNICEF, facilitated these changes in country, acting individually, or in concert.The adoption of the Option B+ policy marked a departure from established processes for PMTCT policy formulation which had been led by WHO with the support of technical experts, and in which recommendations were developed following shifts in evidence. Rather, changes were spurred by a country-level initiative, and a set of strategically framed arguments that resonated with funders and country-level actors. This bottom-up approach, supported by normative agencies, was transformative. For UNICEF, alignment between the organisation's country focus and the policy's underpinning values, enabled it to work with partners and accelerate widespread policy change.