In a study of open-label Truvada as daily pre-exposure prophylaxis (PrEP) to prevent HIV among 427 young African women and adolescent girls, 95% initiated the HIV prevention strategy, and most used PrEP for the first three months. However, PrEP use fell among participants in this critical population during a year of follow-up clinic visits, although HIV incidence at 12 months was low. The preliminary results suggest that tailored, evidence-based adherence support strategies may be needed to durably engage young African women in consistent PrEP use.