BackgroundThe third United Nations Sustainable Development Goal includes a commitment to end AIDS-related death by 2030. In line with the Goal, Option B+ programs hold a great promise for eliminating vertical transmission of HIV. Option B+ was introduced in 2013 in Ethiopia. The Global Plan identified Ethiopia as one of 22 high priority countries requiring improvement in prevention of mother to child HIV transmission services. Despite HIV treatment being free in Ethiopia, only 59% of children are on treatment. The discrepancies in high uptake of Option B+ and low numbers of children in Ethiopia can be attributed to Loss-to-follow-up, which is estimated from 16 to 80%. While LFTU is expected in the region, no-to-minimal evidence exists on the magnitude and its determinants, which hampers the development of interventions and strategies to reduce LFTU. The purpose of this study is to explore perception of mothers and healthcare providers on determinants of and recommendations to reduce LTFU and HIV exposed infants’ mortality.MethodExplorative, descriptive qualitative study conducted in five zones of Amhara region. The sample consisted of mothers enrolled to the option B+ programs at the five referral hospitals PMTCT departments, nurses and midwives working in those departments, and HIV officers in zonal departments. Data were collected in 2019 using in-depth interviews. Data were analyzed using content analysis and deduced to themes.ResultsOverall, nine themes were identified from the interviews. Five themes represented the determinants of LTFU and mortality while four themes addressed the recommendations to reduce LFTU among mothers and their infant mortality. The determinants themes centered on apathy, stigma and discrimination, poor access to services, healthcare providers behavior and attitudes, and social determinants of health. While recommendations themes suggested that improving access, capitalizing on psychosocial support, education and awareness, and empowerment.ConclusionsSocial and structural issues are major contributors to low retention of mothers and death of children due to HIV. A multi-stakeholder approach, including structural changes, are required to support women and their children to ensure that individuals, communities and country enjoy the full benefits of option B+ and lead to an HIV free generation.