CROI 2018 Abstract eBook

Abstract eBook

Oral Abstracts

38LB URINE-BASED SCREENING FOR TUBERCULOSIS: A RANDOMIZED TRIAL IN HIV-POSITIVE INPATIENTS Ankur Gupta-Wright 1 , Elizabeth L. Corbett 1 , Joep J. van Oosterhout 2 , Doug K. Wilson 3 , Daniel Grint 1 , Melanie Alufandika-Moyo 2 , Jurgens A. Peters 1 , Lingstone Chiume 4 , Stephen D. Lawn 1 , Katherine Fielding 1 1 London School of Hygiene & Tropical Medicine, London, UK, 2 Dignitas International, Zomba, Malawi, 3 Edendale Hospital, Pietermaritzburg, South Africa, 4 Malawi– Liverpool–Wellcome Trust Clinical Rsr Prog, Blantyre, Malawi Background: Tuberculosis (TB) is the major cause of death in people living with HIV (PLHIV), in part due to suboptimal diagnosis. Urine is easily obtained, and urine diagnostics are rapid, complementary to sputum, have good yield, and reflect often-fatal disseminated TB. Urine screening may therefore reduce death and missed TB diagnosis in severely ill PLHIV. Methods: The STAMP trial was a pragmatic, individually randomized controlled trial recruiting consecutive, unselected PLHIV admitted to medical wards in Edendale, South Africa, and Zomba, Malawi. HIV testing was offered if status was unknown. Randomization was stratified by site. Consenting eligible patients (≥18years, not on TB treatment) were allocated to either standard of care (SOC) screening (sputum Xpert MTB/RIF) or intervention arms (SOC plus Determine TB-LAM on neat urine and Xpert MTB/RIF on centrifuged urine) regardless of symptoms. Results were reported as TB screen positive or negative to routine clinicians who managed patients masked to study arm. Mortality (primary outcome) and TB events (secondary) were ascertained at 56 days. Results: We screened 4788 PLHIV and randomised 2600 (1300/arm) from Oct-2015 to Sep-2017. 26 were excluded, leaving 2574 PLHIV for final analysis, of whom 996 (38.7%) had TB suspected and 1861 (72.3%) were on antiretroviral therapy (ART) at admission. Median CD4 was 227 cells/µL. Baseline characteristics did not differ by arm. 27 (1.0%) were lost to follow-up. By 56 days, 272 (21.1%) and 235 (18.3%) patients had died in SOC and intervention arms respectively (risk difference [RD] -2.8%, 95% confidence interval [CI] -5.8 to 0.3, p=0.07; odds ratio 0.83, 95% CI 0.7 to 1.0). Intervention armmortality was significantly lower than SOC in pre-specified subgroups: CD4<100 cells/µL (RD -7.1%, 95% CI -13.7 to -0.4); haemoglobin <8g/dl (RD -9.0%, 95% CI -16.6 to -1.3); and TB clinically suspected at admission (RD -5.7%, 95% CI -11.0 to -0.5) (Table). TB diagnosis was significantly more likely in intervention (21.9%) than SOC (14.9%) arm (RD 7.3%, 95% CI 4.4 to 10.2%, p<0.001). Differences in TB diagnosis between arms were not confined to any particular subgroups. Conclusion: Systematic urine screening of hospitalised PLHIV increased overall TB diagnosis and treatment, and reduced mortality in key subgroups despite high ART coverage. Early mortality differences were minimal outside of these subgroups, although reducing missed TB diagnoses is likely to be of wider value. Trial registration: ISRCTN71603869

of isoniazid (H)/ rifapentine (P) would be non-inferior to 9 months H in people with HIV infection. Methods: This multicenter, randomized, open-label, phase 3 trial enrolled HIV-infected individuals >13 y living in high TB-burden areas or who were TB skin test (TST)/Interferon- ϒ release assay (IGRA) positive. Antiretroviral therapy (ART) with efavirenz or nevirapine was permitted. Participants (pts) were stratified by ART status and CD4 count, randomized 1:1 to 1 month of daily H 300 mg plus P 450-600 mg (1HP) or 9 months daily H 300 mg (9H), and followed until 3 y after the last enrollment. The primary objective was to compare incidence rates (IR) of active TB, TB death, or death from an unknown cause. TB diagnoses and deaths were reviewed independently. A non-inferiority margin of 1.25/100 PY was based on an assumed IR of 2.0/100 PY in the 9H arm. Results: 3000 pts were recruited by 45 sites in 10 countries from 5/2012- 11/2014 and data are current as of 12/20/2017. 1614 (54%) were women, median age was 35 y (IQR 28-43), 1983 (66%) were Black, 730 (24%) Hispanic, and median BMI was 23.5 (IQR 20.9-27.1). Median CD4 count was 470 cells/mm 3 (IQR 346-635) and 50%were on ART at entry. 634 (21%) had positive TST or IGRA. The primary endpoint occurred in 34 pts in the 1HP arm and 35 in the 9H arm, for incidence rates of 0.69/100 PY for 1HP and 0.72/100 PY for 9H (IR difference = -0.025, upper 95% CI: 0.31, Table). Rates were higher for pts not on ART at entry and those with a positive TST/IGRA, with no difference between treatments. For those with baseline CD4 counts <250 cells/mm 3 , incidence was higher in the 1HP arm, but the difference was not statistically significant (p=0.12). Serious adverse events occurred in 5.6% of 1HP pts and 7.1% of 9H pts (p=0.1). The incidence of targeted safety events was 3.3/100 PY with 1HP and 5.1/100 PY with 9H (P=0.03); treatment completion was higher in the 1HP arm than 9H (97% vs. 90%, P<0.01). There was 1 case of rifampin-resistant TB in each arm and 1 case of H-resistant TB in the 9H arm. Conclusion: Once daily 1HP was non-inferior to 9H, had fewer adverse events, and was more likely to be completed in HIV-infected adults and adolescents. This ultra-short course TB preventive therapy could be an important tool to control HIV-related TB.

Oral Abstracts

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CROI 2018