Background: The WHO recommends the urine lipoarabinomannan assay Determine™ TB LAM Ag (Determine-LAM) to help diagnose tuberculosis in people living with HIV. A new assay, SILVAMP TB LAM (SILVAMP-LAM)*, may serve as a replacement test for Determine-LAM. Two recently developed methods allow assessing certainty of evidence in comparative accuracy reviews: QUADAS-C and GRADE for comparative accuracy.
Objectives: To compare the accuracy of Determine-LAM and SILVAMP-LAM for diagnosing tuberculosis in adults living with HIV.
Methods: We searched 10 databases and registries in June 2021. We included studies comparing Determine-LAM and SILVAMP-LAM in adults living with HIV. We used two reference standards: microbiological (culture, nucleic acid amplification test, or both on any specimen type) and composite (microbiological or other tests or clinical assessment). We independently assessed study quality using QUADAS-2 and QUADAS-C. We estimated summary sensitivity, summary specificity, and their absolute differences using a Bayesian bivariate model. Using GRADE, we assessed certainty that the true difference in accuracy lies within the range of the 95% credible interval (CrI).
Results: We included five comparative accuracy studies. Using QUADAS-C, risk of bias was high in two. We present comparative accuracy estimates based on the microbiological reference standard; those based on the composite reference standard were similar. Based on four fully paired studies in inpatient settings (1021 participants, 619 cases), difference in summary sensitivity between SILVAMP-LAM and Determine-LAM was 26.5% (CrI 5.1% to 44.9%; moderate certainty) and difference in summary specificity was -4.4% (CrI -14.2% to 5.3%; moderate certainty). Based on three fully paired studies in outpatient settings (627 participants, 124 cases), difference in summary sensitivity and difference in summary specificity were 42.9% (CrI 11.4% to 66.5%; low certainty) and -4.8% (CrI -16.1% to 2.6%; low certainty).
Conclusions: In adults with HIV in inpatient settings, SILVAMP-LAM likely has higher sensitivity than Determine-LAM and specificity that likely ranges from lower to similar to that of Determine-LAM. In outpatient settings, SILVAMP-LAM may have higher sensitivity than Determine-LAM and specificity that may range from lower to similar to that of Determine-LAM. Results of an updated search will be presented at the meeting. Patient involvement: none. *Not commercially available.