**4. Conclusions**

The NOP formulation is an acceptable and age-appropriate dosage form to replace the OS for pediatric patients or patients who may have difficulties in swallowing a tablet. The majority of key design targets were achieved for the development program and suitable palatability assessments (flavor profile method) were executed. The development and taste assessment work conducted for the NOP complements the extensive work previously performed for OS. While it was not feasible to substantially improve the palatability of the formulation itself, there may be widely available options for patients to reduce the lingering bitterness.

NOP may be added to soft food (applesauce, vanilla pudding) or suspended in a liquid (water, infant formula, chocolate milk) as a convenient method for dose administration, though the effects on bitterness reduction were determined in previous studies to be modest. In this study, a variety of beverages and soft foods and consumed immediately after NOP dosing (peanut butter, hazelnut chocolate spread, black currant fruit drink concentrate, golden syrup, and chocolate syrup) were shown to reduce the intensity and duration of the bitter aftertaste, most notably peanut butter and hazelnut chocolate spread. The variety of beverages and soft foods as vehicles, as well as those taken immediately after dosing, offers patients more choices according to their individual taste preferences.

In summary, the NOP pediatric formulation provides dosing flexibility, enhanced stability and commercial shelf life under long term global climatic (30 ◦C/75% RH) storage conditions to support use in tropical climates of Africa where more than 95% of children with HIV live, and absence of propylene glycol and ethanol. It maintains consistent bioavailability when administered with a wide variety of vehicles and improved palatability when common food products were employed as "chasers" following dose administration.

**Author Contributions:** Conception and design, J.B.M. and J.H.W.; Collection and assembly of data, J.B.M., D.A.T. and J.H.W.; Investigation, D.C.T.T.; Manuscript writing; all authors, Final approval of the manuscript; all authors. Accountable for all aspects of the work; all authors.

**Funding:** This research received no external funding.

**Conflicts of Interest:** John B. Morris and David Cheng Thiam Tan are employees of AbbVie Inc. and may own AbbVie stock options. David A. Tisi and Jeffrey H. Worthington are employees of Senopsys LLC. AbbVie sponsored and funded the study; contributed to the design, participated in the collection of data. AbbVie and Senopsys participated in the interpretation of data, in writing, reviewing, and approval of the final publication.
