Little is known about associations between viral suppression, adherence, and duration of prior viral suppression in sub-Saharan Africa. Study participants were from the UARTO study in Mbarara, Uganda. We fit regression models to characterize relationships between average adherence, treatment interruptions, and rebound viremia (>400 copies/mL) following a previously undetectable result. Our goal was to understand the impact of prior viral suppression on these relationships. 396 participants contributed 2864 quarterly visits. Restricted to periods with average adherence <50 %, each 10 % increase in adherence reduced the odds of rebound viremia by 74 % [adjusted odds ratio (AOR) = 0.26, P = 0.002] and 29 % (AOR = 0.71, P = 0.057) during the first 12 months of suppression and beyond 12 months respectively, interaction term P = 0.018. Among periods with adherence ≥50 %, the risk of rebound viremia decreased with increasing adherence during the first 12 months of viral suppression (AOR = 0.73 for each 10 % increase, P = 0.001), but not thereafter (AOR = 1.09, P = 0.67), interaction term P = 0.027. In contrast, 72-h interruptions, were associated with increased rebound viremia during the first 12 months (AOR = 1.30, P = 0.009) and after (AOR = 1.39, P = 0.005), interaction term P = 0.69. Completing 12 months of viral suppression decreases the impact of average adherence, but not prolonged treatment interruptions, on risk of rebound viremia.