Successful rollout of anti-retroviral therapy (ART) in Africa has resulted in a steep decline in HIV incidence. Even though this has been a long-awaited development, it is not the case for adolescents (10-19 years) born HIV-positive. Given this brief background and dangers imposed by COVID-19 pandemic, adolescents born HIV-positive are at great risk. A systematic review was conducted and reported, according to preferred reporting items for meta-analyses (PRISMA). Studies were drawn from database search performed between April and June 2020 using PsycINFO, Google Scholar, and Sabinet. Results suggested that factors, which negatively impact ART adherence fall into three main levels: 1. Household level: through pressure to share medication; 2. Institutional level: lockdown restrictions due to COVID-19, long distance to facilities, heavy workload due to limited staff, and extended waiting times; 3. Community level: structural barriers, such as HIV stigma and discrimination, gender inequalities, and poor living conditions. Main motivators to remain adherent to ART include having a strong social support system, life goals, and ambitions. This paper highlights the complexity of ART adherence during COVID-19 pandemic. Interventions to improve adherence to ART of adolescents born HIV-positive should address psycho-social factors, such as treatment fatigue, disclosure and family, and household dynamics, in addition to access to ART service delivery during periods of crisis.