CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

such as heart failure and constriction need to be studied beyond the end of TB treatment.

875

Changes in Physical and Mental Health Among TB Patients During Treatment in Southern Africa Nicolas Banholzer 1 , Guy Muula 2 , Denise Evans 3 , Jacqueline Huwa 4 , Idiovino Rafael 5 , Cordelia Kunzekwenyika 5 , Ballif Marie Ballif 1 , Gunar Günther 6 , Matthias Egger 1 , Lukas Fenner 1 , for IeDEA Southern Africa (IeDEA-SA) 1 Institute of Social and Preventive Medicine, Bern, Switzerland, 2 Center for Infectious Disease Research in Zambia, Lusaka, Zambia, 3 Health Economics and Epidemiology Research Office, Johannesburg, South Africa, 4 Lighthouse Trust Clinic, Lilongwe, Malawi, 5 SolidarMed, Luzern, Switzerland, 6 University Hospital of Bern, Bern, Switzerland Background: Tuberculosis (TB) contributes to high morbidity and mortality worldwide. TB may also impair people's quality of life (QoL) and physical fitness. We studied the change in health-related QoL and functional exercise capacity (cardio-pulmonary function) in TB patients living with and without HIV between treatment start and end. Methods: We recruited people with TB aged ≥15 years between October 2022 and July 2023 in five ongoing cohorts in Zambia, South Africa, Malawi, Mozambique, and Zimbabwe. At the start (baseline) and end of TB treatment, we measured physical and mental health outcomes using the standardized QoL Short Form Health Survey (SF-12), depression using the Patient Health Questionnaire (PHQ-9), and physical fitness using the 6-min walk test (6MWT). We also collected age, sex, HIV status, type of diagnosis (clinical vs microbiologically confirmed), chest X-ray findings, and TB multidrug resistance. We estimated changes in the QoL physical (QoL-PCS) and mental (QoL-MCS) t-score component, the depression score (PHQ9-S), and 6MWT distance (6MWT-D) between the start and end of TB treatment. We estimated the association of these changes with baseline characteristics using Bayesian multivariable log-linear regression models and cohort-specific random effects. Results: We included 200 TB patients with at least one outcome at the start and end of treatment. Overall, the median age was 36 years (Interquartile Range [IQR]: 28-43 years), 55 (27%) female, 79 (40%) living with HIV, 101 (51%) were clinically diagnosed, 34 (17%) had lung cavitations, and 3 (1%) presented with TB drug resistance. At treatment start, overall median QoL-PCS was 37 (IQR 29-43), QoL-MCS was 44 (IQR 39-50), PHQ9-CS was 6 (IQR 3-10), and 6MWT-D was 400m (IQR 332-464). QoL-PCS increased by 39% (95%-Credible Interval [CI] 35-44%), QoL-MCS by 19% (95%-CI 16-22%), 6-MWT-D by 15% (95%-CI 8-22%), and PHQ9-S decreased by 26% (95%-CI 22-31%) (Figure A). Lung cavitations tended to be negatively associated with improvements in QoL and physical fitness, and female gender was negatively associated with QoL-MCS (Figure B). Recruitment and study visits six months after completion of TB treatment are ongoing. Conclusion: QoL and physical fitness were reduced at the start of treatment in South African TB patients but improved by the end of treatment. More emphasis should be placed on improving clinical management with respect to QoL and mental health aspects during and after TB treatment.

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Efficacy and Safety of endTB Regimens for Fluoroquinolone-Susceptible RR-TB in People With HIV Gustavo E Velásquez 1 , M Gouillou 2 , E Berikova 3 , M Bonnet 4 , N Lachenal 5 , L Lecca 6 , L Oyewusi 7 , Michael L. Rich 8 , Naseem Salahuddin 9 , Kwonjune J. Seung 8 , Sean Wasserman 10 , Francis Varaine 11 , Lorenzo Guglielmetti 11 , Carole D. Mitnick 12 , for the endTB Clinical Trial Group 1 University of California San Francisco, San Francisco, CA, USA, 2 Epicentre, Paris, France, 3 Partners In Health, Astana, Kazakhstan, 4 Université de Montpellier, Montpellier, France, 5 Médecins Sans Frontières – Switzerland, Geneva, Switzerland, 6 Socios en Salud Sucursal Peru CRS, Lima, Peru, 7 Partners In Health, Maseru, Lesotho, 8 Partners In Health, Boston, MA, USA, 9 Indus Hospital, Karachi, Pakistan, 10 St. George's University of London, London, United Kingdom, 11 Médecins Sans Frontières – France, Paris, France, 12 Harvard Medical School, Boston, MA, USA Background: endTB (NCT02754765) was an open-label Phase 3 randomized, controlled clinical trial to evaluate the efficacy and safety of five 9-month, all-oral regimens for fluoroquinolone-susceptible rifampin-resistant TB, compared to the WHO-recommended standard of care, in people 15 years of age or older. In the primary analysis, three experimental regimens (9BLMZ, 9BCLLfxZ, and 9BDLLfxZ) had noninferior efficacy compared to the control and were safe. Here, we present efficacy and safety results among people with HIV (PWH). Methods: endTB inclusion was irrespective of HIV status or CD4 count. The safety population included all randomized participants who started study treatment, and the modified intention-to-treat (mITT) population included those in the safety population who had a positive pre-randomization TB culture and no resistance to study drugs. The primary efficacy endpoint was favorable outcome at Week 73 post-randomization, defined as either [1] two consecutive, negative cultures (one between Weeks 65 and 73); or [2] favorable evolution. Unfavorable outcomes included death, treatment failure, drug addition/ replacement, and retreatment. Safety outcomes were Grade 3-4 adverse events (AEs); serious AEs (SAEs); deaths; AEs of special interest (AESIs) defined as Grade 3-4 hepatotoxicity, myelosuppression, optic neuritis, peripheral neuropathy, or prolonged QTcF; and AEs leading to permanent discontinuation of at least one drug. Results: From 2017-2021, we randomized 754 participants in 7 countries; 104 (13.8%) were PWH. The safety population included 103 (99.0%) and the mITT 98 (94.2%). Median age was 39 years (range 19-70 years); 46 (46.9%) were female; median CD4 count was 296 (range 5-1294); and 61 (62.2%) were on antiretrovirals at baseline. Two of the noninferior experimental arms from the endTB trial demonstrated high efficacy in PWH, with favorable outcomes in 93.3% (9BLMZ) and 100.0% (9BCLLfxZ). The remaining three experimental arms and the control also performed well but showed relatively lower efficacy: 70.6% (9BDLLfxZ), 83.3% (9DCLLfxZ), 73.3% (9DCMZ), and 89.5% (control). Grade 3-4 AEs, SAEs, AESIs, and AEs leading to drug discontinuation were more common in the control than in experimental arms. Conclusion: Among regimens that were noninferior to the WHO control in the primary analysis, 9BLMZ and 9BCLLfxZ appeared to be particularly efficacious and safe for PWH. Additional research is needed to establish optimal all-oral shorter regimens in PWH.

Poster Abstracts

CROI 2024 271