PROJECT SUMMARY/ABSTRACT The convergence of the global HIV and tuberculosis (TB) epidemics represents one of the most urgent challenges facing global public health. Despite improved access to antiretroviral therapy (ART), TB remains the leading killer of children with HIV. Furthermore, the task of treating children co- infected with HIV and TB remains particularly challenging due to lack of optimal treatment regimens. As a result, the World Health Organization (WHO) has designated the evaluation of newer treatment options for children a research priority. To address this issue, we will combine programmatic and pharmacokinetic (PK) analyses to critically evaluate both current and promising future treatment regimens. We will assess current pediatric HIV/TB co-treatment options by examinig 10 years of treatment data from over 5500 pediatric patients enrolled in the Harvard/AIDS Prevention Initiative in Nigeria (APIN) program to identify predictors of HIV/TB treatment failure and/or mortality, with a particular focus on ART timing and regimen selection. We will also evaluate the pharmacokinetics, safety, and efficacy of two novel treatment strategies among co-infected children: (1) rifabutin-based TB treatment in combination with LPV/r-based ART; and, (2) dolutegravir-based ART with concurrent rifampin-based TB treatment, building upon emerging results from the IMPAACT P1093 study. This combination of programmatic outcomes and PK analyses will provide critical data to advance the treatment of pediatric HIV/TB co-infection. The Harvard/APIN PEPFAR program has supported HIV care services for over 150,000 people in Nigeria including over 5500 children since 2004. Children enrolled in this program receive free clinical care, antiretroviral therapy, TB screening, and laboratory monitoring. This study will build upon this well-established HIV treatment program to examine issues critical for efforts to improve pediatric HIV/TB outcomes. Nigeria is home to more children living with HIV than any other country, with 60,0000 children newly infected with HIV in 2012 alone. By critically evaluating our current efforts and performing PK studies to evaluate two novel co-treatment regimens, we will gain essential knowledge that may translate into a change in treatment recommendations and begin to curb TB’s devastating toll.