BackgroundOne way of addressing malnutrition among HIV/AIDS patients is through the Food by Prescription program (FBP) and many studies have explained the treatment outcomes after therapeutic food supplementation, though available evidences on adherence levels and factors associated with these sorts of programs are limited. The findings of this study would therefore contribute to the existing knowledge on adherence to Ready-to-Use Therapeutic/Supplementary Food (RUF) in Ethiopia.MethodsA facility-based, cross-sectional study supplemented with qualitative methods was conducted among 630 adult HIV + patients. Their level of adherence to RUF was measured using the Morisky 8-item Medication Adherence Scale (MMAS-8). The total score on the MMAS-8 ranges from 0 to 8, with scores of <6, 6 to <8, and 8 reflecting low, medium, and high adherence, respectively. Patients who had a low or a moderate rate of adherence were considered non-adherent.ResultsThe level of adherence was found to be 36.3% with a 95.0% response rate. With the exception of the educational status, other socio-demographic variables had no significant effect on adherence. Those who knew the benefits of the FBP program were 1.78 times more likely to adhere to the therapy than the referent groups. On the other hand, patients who were not informed on the duration of the treatment, those prescribed with more than 2 sachets/day and had been taking RUF for more than 4 month were less likely to adhere. The main reasons for non-adherence were not liking the way the food tasted and missing follow-up appointments. Stigma and sharing and selling food were the other reasons, as deduced from the focus group discussion (FGD) findings.ConclusionThe observed level of adherence to the FBP program among respondents enrolled in the intervention program was low. The major factors identified with a low adherence were a low level of education, poor knowledge on the benefits of RUF, the longer duration of the program, consuming more than two prescribed sachets of RUF per day, and not being informed about the duration of the treatment. Therefore, counseling patients on the program’s benefits, including the treatment plans, would likely contribute to improved adherence.