Urine LAM Testing in Advanced HIV Positive Adults in a Trial of Empiric TB Therapy.

BACKGROUND The urine lipoarabinomannan (LAM) antigen test is a TB diagnostic test with highest sensitivity in individuals with advanced HIV. Its role in TB diagnostic algorithms for HIV positive outpatients remains unclear. METHODS ACTG A5274 trial demonstrated that empiric TB therapy did not improve 24-week survival compared to isoniazid preventive therapy (IPT) in TB screen negative HIV positive adults initiating ART with CD4 counts <50 cells/µL. Retrospective LAM testing was performed on stored urine obtained at baseline. We determined the proportion of LAM-positive participants and conducted modified intent-to-treat analysis excluding LAM-positive participants to determine the effect on 24-week survival, TB incidence and time to TB using Kaplan-Meier method. RESULTS A5274 enrolled 850 participants, 53% were male and median CD4 count was 18 cells/µL (IQR: 9, 32). Of the 850, 566 (67%) had LAM testing (283 per arm); 28 (5%) were positive [21 (7%); 7 (2%) in empiric and IPT arms, respectively]. Of those LAM-positive, 1 participant in each arm died and 5 of 21 and 0 of 7 in empiric and IPT arms, respectively, developed TB. After excluding these 28 cases, there were 19 and 21 deaths in empiric and IPT arms, respectively (p=0.88). TB incidence remained higher (4.6% vs. 2%, p=0.04) and time to TB remained faster in the empiric arm (p=0.04). CONCLUSIONS Among outpatients with advanced HIV who screened negative for TB by clinical symptoms, microscopy and Xpert testing, LAM testing identified an additional 5% of individuals with TB. . Positive LAM results did not change mortality or TB incidence.