Participants 18year old+ Screening for tuberculosis with Xpert MTB/RIF versus fluorescent microscopy among people newly diagnosed with HIV in rural Malawi: a cluster-randomized trial Lucky G. Ngwira, Elizabeth L. Corbett, McEwen Khundi, Grace L. Barnes, Austin Nkhoma, Michael Murowa, Silvia Cohn, Larry Moulton, Richard E. Chaisson, David W. Dowdy IAS Conference Poster Discussion, Maillot Room 26th July 2017, Paris, France. Background/ Research Q: Study design CONSORT flow chart: TB is the leading cause of death among people with HIV 1.8 million TB deaths: 0.4 million (22%) in PLHIV 1.1 million HIV deaths; 35% due to TB Xpert MTB/RIF more sensitive for TB diagnosis Sensitivity: -88% as replacement test -67% as an add-on test Reduces time to diagnosis relative to sputum smear microscopy Multiple clinical trials have shown no mortality benefit relative to sputum smear microscopy Research Question: Does screening for TB with Xpert MTB/RIF v LED FM reduce mortality in Malawi among adults recently diagnosed with HIV? Cluster randomised trial in 12 public health clinics (6 per arm: Xpert MTB/RIF & LED FM) Rural district of Thyolo, Malawi Adults, newly diagnosed with HIV: -All participants screened for TB -If symptomatic, point-of-care (POC) Xpert MTB/RIF or LED FM depending on arm -If asymptomatic & eligible, IPT -Follow up for 1 year -Primary outcome: All-cause mortality -Secondary outcome: All-cause mortality in subgroups according to age, sex, and WHO clinical stage Participants 18year old+ -Newly diagnosed with HIV -Eligibility assessment/ Informed consent -WHO clinical staging Newly diagnosed HIV+ve patients assessed for eligibility: 3040 Excluded (n=1149) Not from traceable area (n=583) Under 18 years (n=254) Refused consent (n=153) Other (132) Not enrolled for other reasons (n=49) Randomised: 1842 (6 clinics per arm) Xpert Arm: 1001 LED Arm: 841 Diagnosed with prevalent TB: 24 (2.4%) Person-years follow up: 823 Incident cases of TB diagnosed: 8 Diagnosed with prevalent TB:12 (1.4%) Person-years follow up:697 Incident cases of TB diagnosed: 12 WHO, Global TB Report, 2016 Steingart, Coch Database Syst Review 2014 Schumacher et al, PLOS ONE 2016

Results Xpert arm (1001) LED FM arm (841) Baseline characteristics Rate ratios for all-cause mortality (95% CI)  Characteristic• Xpert Arm (n=1001) LED Arm (n=841) Age in years 33 (27-40) 32 (26-40) Gender Male Female (non pregnant) Female (pregnant)   410 (41%) 434 (43%) 157 (16%) 309 (37%) 369 (44%) 163 (19%) WHO staging at enrollment 1 or 2 3 or 4  707 (71%) 290 (29%)  656 (79%) 173 (21%) General Health at enrollment Excellent Good Fair Poor  81 (8%) 495 (49%) 378 (38%) 47 (5%)  108 (13%) 261 (31%) 103 (12%) 0.83 (0.63, 1.09) 0.86 (0.47, 1.58) 0.73 (0.48, 1.11) 0.49 (0.28, 0.87) 1.19 (0.79, 1.78) 1.07 (0.55, 2.07) 0.46 (0.22, 0.93) •All other characteristics including CD4 count at baseline (WHO stage 1 or 2 only), smoking, previous TB treatment and TB symptoms were similar between the two arms Primary trial events (All) Kaplan-Meier survival rates by arm and clinical stage   Xpert arm (1001) LED FM arm (841) 12-month mortality (per 100 person yrs) 6.5 7.8 TB diagnosed 32 (3.2%) 22 (2.6%) Prevalent TB 24 (2.4%) 10 (1.2%) Incident TB 8 (0.8%) 12 (1.4%) IPT initiation 749 (75%) 664 (80%) in days

Discussion Limitations Conclusion Acknowledgements Screening for TB among rural adult Malawians newly diagnosed with HIV with POC Xpert MTB/RIF v LED FM: Did not significantly affect all-cause mortality overall (Rate ratio 0.83, 95%CI: 0.63-1.09; p=0.14) Reduced mortality among individuals with stage 3 or 4 disease by 54% (Rate ratio 0.46, 95%CI: 0.22-0.93; p=0.03) Majority of deaths occurred within 1-6 months within stage 3 or 4 of disease Small number of clinics (n=12) Large number excluded, majority coming from non-traceable area Potential lack of generalizability to outside of rural sub-Saharan Africa Screening for TB among rural adults in Malawi recently diagnosed with HIV using point-of-care Xpert MTB/RIF (relative to LED FM) did not reduce overall all-cause mortality in this population but increased the number of people diagnosed with TB at baseline and reduced mortality among individuals with WHO stage 3 or 4 disease. Acknowledgements This study received NIH funding through NIAID (R01 AI093316) and the Johns Hopkins Center for AIDS Research (P30 AI094189) Collaborators: Mw, College of Medicine Malawi Min of Health Participants Study staff