Feasibility of using determine-TB LAM test in HIV-infected adults in programmatic conditions Mathabire SC1, 2, Cossa L³, Mpunga J⁴ , Manhica I⁵, Amoros Quiles I², Molfino L⁶, Szumilin E⁷, Telnov A8, Huerga H¹ ¹Clinical Research Department Epicentre, Paris France; ²Médecins Sans Frontières, Chiradzulu Malawi; ³Médecins Sans Frontières, Maputo Mozambique; ⁴National TB Control Program Malawi; ⁵National TB Control Program, Mozambique; ⁶Médecins Sans Frontières, Maputo Mozambique; ⁷Médecins Sans Frontières Paris France; ⁸Médecins Sans Frontières, Geneva Switzerland

No conflicts of interest to declare Conflict of Interest No conflicts of interest to declare

Background TB diagnosis is a challenge in resource-limited countries Determine TB- Lipoarabinomannan (LAM): performed on urine results in 25 minutes LAM test accuracy (only HIV-positive): Sensitivity: 4.0 - 66.7% (depending on CD4 count) Specificity: >98% WHO policy guidance (Nov 2015) on LAM test for HIV-positive: Low CD4 count or Severely ill regardless of their CD4 count

Aim To assess the feasibility of using the LAM test in programmatic conditions

Methods Design: Population: HIV-positive adult patients Multi-centric prospective longitudinal studies Malawi and Mozambique 2014 to 2016 Population: HIV-positive adult patients Regardless of TB symptoms : All hospitalized (Malawi) Ambulatory with CD4<100/µl (Mozambique) TB suspects: Ambulatory with CD4 <200 /µl (Malawi and Mozambique)

Methods/ Context Malawi: Chiradzulu District Hospital IPD Hospital OPD 3 PHCs Mozambique: Chamanculo District Centre of Reference Alto-Maé (CRAM) 1 PHC LAM performed in laboratory or consultation rooms

Methods/ Data collection & analysis Mixed methods: Minutes of trainings, interviews of trainees Description of training required before using LAM test Self administered standard questionnaire Assessment of user acceptability of LAM Study electronic databases % agreement between 2 LAM readers , Kappa (95%CI)

Methods/ Data collection & analysis LAM test Turnaround time (TAT) Interval from urine request to clinician getting result Health centre registers, interviews with LAM users Estimate daily workload attributed to LAM test Supervision notes, minutes of meetings, and personal observations Space/ extra equipment required to perform LAM test Strengths and challenges of using LAM

Results/ training Training time: 1.5 hours in Malawi 4 hours in Mozambique. Prior reading of test SOP 20- 30 minutes explanation of LAM Practical *Correct use of reference card challenging Urine loading pad Control window Patient window

Results/space and equipment

Results/LAM ease of use 20/20: test easy or very easy to use 4/20: difficult to distinguish Grade 1 or lighter than Grade 1 No extra space required Test arrived in field with 1 year expiry No need for special storage as it is a small packet Final result … Positive or Negative? 18% Malawi & 8% Mozambique had line fainter than Grade 1

Results/LAM reader agreement Test grade (no line to line Grade 4) 95.2%, kappa=0.91 (95%CI 0.90-0.92) in Malawi 97.2%, kappa=0.95 (95%CI 0.94-0.96) in Mozambique Test interpretation (positive or negative) 98.9%, kappa=0.97 (95%CI 0.96-0.98) in Malawi 98.3%, kappa=0.96 (95%CI 0.95-0.98) in Mozambique

Results/ additional workload Malawi OPD/PHC: 27 minutes (11.3 %) IPD: 66 minutes (25.4 %) Mozambique OPD: 26 minutes (9.5%) *Workload calculation took into account the time used for clinical consultation only Malawi OPD: 27 minutes (11.3 %) (1x27)/(30x8) IPD: 66 minutes (25.4 %) (2x33)/(13x20) Mozambique OPD: 26 minutes (9.5%) (1x26)/(11x25)

Results/ LAM Strengths Rapid results TB treatment on same day Decreased visits before diagnosis → reduced cost for patients Higher proportion of LAM results TAT for LAM Laboratory: 100 - 155 min Bedside: 35 - 44 min TAT for sputum: 2 days TAT chest X-ray: 4 days Malawi lab IPD=140min Malawi lab OPD=92 min Malawi lab PHC= 222min Moza lab CRAM=84 Moza OPD=46

Results/ LAM Challenges Prior CD4 needed to identify LAM eligible patients High demand for CD4 tests (Mozambique) → patients asked to come following day CD4 test result TAT→ 2 hours Test and Treat policy → CD4 tests stopped (Malawi) Urine collection from very sick or unconscious patients Reading card not used prior to study Female patients reluctant to give urine during menses

Conclusions Can be implemented in hospital, PHCs Feasible Easy to perform Results same day Minimal logistics Most submit urine Minimal workload Difficulty discriminate Grade1 line Can be implemented in hospital, PHCs Performed by nurses, clinical officers, doctors Consider task shifting of LAM Partial reliance on CD4 count Retain and prioritize CD4 testing for LAM eligible patients

All staff who participated Acknowledgements NTP Malawi, Mozambique Chiradzulu DHMT Maputo DSCM All staff who participated The patients Maputo DSCM “ direccao saude da cidade de