The trajectory of pediatric HIV infection, care, and treatment varies from that of adults on multiple levels, including by geography. In Asia, pediatric antiretroviral treatment was slowly scaled up from the early 2000s, and those with perinatally acquired HIV now live with the legacies of local delays in diagnosis and treatment. Sustained treatment adherence is central to HIV control, but growing up with HIV and the associated stigma make this especially challenging. When treatment fails, children are at greater risk of opportunistic infections, often leading to pneumonia and sepsis, which are the most common causes of death in Asian adolescents living with HIV. Life-long HIV also is associated with other conditions, such as persistent infection with human papillomavirus, which leads to abnormal cervical cytology and risk of anogenital cancer. Compounding the medical challenges are HIV-related stigma and discrimination, which can lead to social isolation from a young age. Data from Southeast Asian youth soon after transition from pediatric to adult HIV care have shown that most hide their HIV status from others. Their fear of disclosure escalates as they become more socially exposed in their communities, and shapes their daily interactions. In addition to the policy and practice changes needed to improve the quality of global and national HIV surveillance data and comprehensiveness of clinical care, research on treatment outcomes of Asian adolescents with perinatally acquired HIV should include studying co-morbidities and co-infections to better understand how related risks and behaviors intersect to impact HIV viral suppression, retention, and survival.