Background: Orphan status is usually a risk factor for many diseases and results in social exclusion and worse outcomes than children with parents. Methods: The case reports of severe toxicity where death was averted by close monitoring in an orphanage in Phnom Penh, Cambodia are presented. Results: Close monitoring of adherence of antiretroviral therapy (ARV) is possible only in close facility, e.g. orphanage, where regular DOT (directly observed therapy) and DOTOX (directly observed toxicity) is possible. Conclusions: Three cases of severe toxicity: two bone marrow severe suppression and one cardiomyopathy are presented. Deaths were averted by close observation and early interventions.