BackgroundHuman immunodeficiency virus-infected children share the highest risk of death compared with all other age groups, and more than 90% of this viral infection of children was accounted for by transmission from mother to infant. This rate can be prevented and reduced with implementation of option B+ effectively. However, unacceptably high lost follow-up of mothers highly affected the effectiveness of this program. In Ethiopia, only 71% of mothers were adherent on their follow-up. So, this study was aimed to understand the reasons and experiences of lost follow-up of mothers under the prevention of mother to child transmission (option B+) program in North West Ethiopia.MethodsA qualitative study using a case study design was carried out using in-depth interviews among 20 mothers who had started the option B+ treatment protocol but discontinued their follow-up for more than two months, and 6 key informants and individuals who were engaged in management and control of human immunodeficiency virus at Woreda and Zonal level. An unstructured interview guide was used and translated into the local language. Study participants were selected using purposive sampling technique. After written consent was obtained, all study participants’ interviews were audio-recorded and analyzed using deductive content analysis.ResultsA total of 26 mothers participated in this study. Accordingly, the most frequently raised reasons were lack of formal education which affects income level, lack of disclosure, lack of partner and family support, absence of male involvement and stigma-discrimination. But, unavailability of option B+ regimens in the nearest health facility or long distance from health facility, discordance and lack of experienced professionals in terms of counseling during initiation were also essential reasons.ConclusionEducational and economic empowerment intervention (particularly for vulnerable households), promoting family support and male involvement, active counseling at initiation and during follow up and community level awareness improvement should be addressed to increase option B+ regimen adherence and retention.