1. 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: (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

2. 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

3. 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: ; p=0.14)
Reduced mortality among individuals with stage 3 or 4 disease by 54% (Rate ratio 0.46, 95%CI: ; 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