PEPFAR

Tuberculosis (TB) is the leading killer of PLHIV globally, accounting for nearly a quarter of all deaths. To reduce the impact of TB, the WHO recommends intensified case finding (ICF) for all PLHIV (i.e., symptombased TB screening at every clinical encounter, followed by confirmatory testing of those who screen positive). However, ICF has been challenging to implement in sub-Saharan Africa because testing the 70- 90% of PLHIV who are symptom screen-positive for active TB is beyond the capacity of most HIV/AIDS programs. Moreover, Xpert MTB/RIF - the recommended first-line TB test for PLHIV - misses a substantial proportion of TB cases when used in the context of ICF. The overall objective of this proposal is to determine whether novel and low-cost point-of-care (POC) assays to measure serum C-reactive protein (CRP) and urinary lipoarabinomannan (LAM) optimize TB screening and testing strategies for ICF. The central hypothesis is that TB screening based on serum CRP levels and TB testing inclusive of measuring urinary LAM will be cost-effective relative to the current standard for ICF (symptom-based screening followed by testing with Xpert) among PLHIV in urban Uganda. In Aims 1 and 2, the infrastructure established by an ongoing pilot study of CRP-based TB screening in Kampala, Uganda will be leveraged to enroll and follow 1250 consecutive PLHIV. All study participants will be screened for TB using the WHO symptom screen and POC CRP and tested for TB by smear microscopy, Xpert MTB/RIF, Determine TB-LAM (if CD4 count <200 cells/µl) and liquid culture. The comparative effectiveness (i.e., diagnostic accuracy, time-to-result) of TB screening (Aim 1) and testing strategies (Aim 2) will be evaluated in reference to liquid culture results. In Aim 3, empirical costing studies of combined TB screening and testing algorithms for ICF will be conducted. The cost data will be used along with effectiveness data from Aims 1 and 2 and published estimates of HIV/TB outcomes to determine the cost-effectiveness of novel ICF algorithms relative to the current standard for ICF and to no ICF (i.e. passive case detection). Completion of these aims will enable PEPAR programs to most effectively and efficiently implement ICF in Uganda and other target countries.