Key PointsQuestionDoes 6-month daily oral HIV preexposure prophylaxis (PrEP) dispensing supported with interim HIV self-testing reduce the number of annual PrEP clinic visits without jeopardizing client continuation outcomes at 12 months?FindingsIn a randomized noninferiority trial among 495 adults in Kenya, semiannual PrEP dispensing supported with interim HIV self-testing resulted in noninferior HIV testing and PrEP adherence 1 year after initiation compared with standard quarterly PrEP dispensing.MeaningThe findings of this study suggest that this differentiated model of PrEP service delivery could simplify and optimize PrEP delivery.