Efavirenz-based antiretroviral therapy (ART) is the preferred regimen in children older than 3 years on rifampin-containing anti-TB therapy. Efavirenz trough plasma concentrations below 1000 ng/mL have been associated with increased risk of virologic failure among HIV-infected adults, while concentrations above 4000 ng/mL have been associated with risk of central nervous system side effects. Efavirenz is primarily metabolized by hepatic CYP2B6, with secondary contributions from CYP2A6. On average, rifampin co-administration causes a 26% reduction in efavirenz plasma exposure but some individuals have paradoxically elevated efavirenz concentrations with co-administration in adult pharmacokinetic studies. The inter-individual variability in the drug-to-drug interactions suggest that efavirenz dose adjustment with concomitant anti-TB therapy may not be necessary in some patients. In children, there is very limited data on the pharmacokinetic interactions between rifampin-containing TB treatment and efavirenz. To our knowledge, there is only one published study in children to date. Among 15 TB/HIV co-infected children treated with standard efavirenz-based active antiretroviral therapy and rifampin-containing TB treatment, a wide inter-patient variability in efavirenz concentration as well as a bimodal distribution of efavirenz trough concentrations were observed. Overall, rifampin-containing anti-TB treatment had no significant influence on the mean change in efavirenz concentration in the study population as a whole, but 60% and 53% of children had efavirenz trough concentration < 1000 ng/mL during and after anti-TB, respectively. This data suggest that current dosing of efavirenz may be suboptimal in a large proportion of children irrespective of anti-TB therapy. To overcome the risk of under-dosing of efavirenz especially with concurrent anti-TB treatment, the WHO recommended prescribing the maximum dose for each weight-band when efavirenz is coadministered with anti-TB treatment. This study seeks to evaluate whether the current dosing of efavirenz provides adequate efavirenz concentrations in children, as well as explore how genetic factors influence efavirenz pharmacokinetics with concomitant anti-TB treatment. The specific hypotheses to be tested are: