Completion of isoniazid–rifapentine (3HP) for tuberculosis prevention among people living with HIV: Interim analysis of a hybrid type 3 effectiveness–implementation randomized trial

Background Scaling up shorter regimens for tuberculosis (TB) prevention such as once weekly isoniazid–rifapentine (3HP) taken for 3 months is a key priority for achieving targets set forth in the World Health Organization’s (WHO) END TB Strategy. However, there are few data on 3HP patient acceptance and completion in the context of routine HIV care in sub-Saharan Africa. Methods and findings The 3HP Options Trial is a pragmatic, parallel type 3 effectiveness–implementation randomized trial comparing 3 optimized strategies for delivering 3HP—facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between DOT and SAT using a shared decision-making aid—to people receiving care at a large urban HIV clinic in Kampala, Uganda. Participants and healthcare providers were not blinded to arm assignment due to the nature of the 3HP delivery strategies. We conducted an interim analysis of participants who were enrolled and exited the 3HP treatment period between July 13, 2020 and April 30, 2021. The primary outcome, which was aggregated across trial arms for this interim analysis, was the proportion who accepted and completed 3HP (≥11 of 12 doses within 16 weeks of randomization). We used Bayesian inference analysis to estimate the posterior probability that this proportion would exceed 80% under at least 1 of the 3HP delivery strategies, a coprimary hypothesis of the trial. Through April 2021, 684 participants have been enrolled, and 479 (70%) have exited the treatment period. Of these 479 participants, 309 (65%) were women, mean age was 41.9 years (standard deviation (SD): 9.2), and mean time on antiretroviral therapy (ART) was 7.8 years (SD: 4.3). In total, 445 of them (92.9%, 95% confidence interval (CI): [90.2 to 94.9]) accepted and completed 3HP treatment. There were no differences in treatment acceptance and completion by sex, age, or time on ART. Treatment was discontinued due to a documented adverse event (AE) in 8 (1.7%) patients. The probability that treatment acceptance and completion exceeds 80% under at least 1 of the three 3HP delivery strategies was greater than 99%. The main limitations are that the trial was conducted at a single site, and the interim analysis focused on aggregate outcome data to maintain blinding of investigators to arm-specific outcomes. Conclusions The 3HP was widely accepted by people living with HIV (PLHIV) in Uganda, and very high levels of treatment completion were achieved in a programmatic setting. These findings show that 3HP can enable effective scale-up of tuberculosis preventive therapy (TPT) in high-burden countries, particularly when delivery strategies are tailored to target known barriers to treatment completion. Trial registration ClinicalTrials.gov NCT03934931.

1407. The Latent Tuberculosis Infection Cascade of Care during the COVID-19 Pandemic Response in a Mid-Sized US City

Background The COVID-19 pandemic response may unintendedly disrupt multiple public health services, including tuberculosis control programs. We aimed to assess the cascade of care of latent tuberculosis infection (LTBI) in an urban US city during the COVID-19 pandemic response. Methods We conducted a retrospective cohort study of adult patients who presented for LTBI evaluation at the Hamilton County Public Health Tuberculosis Clinic in Ohio between 2019 and 2020. We defined 01/2019 to 02/2020 as the pre-COVID-19 response period, and 04/2020 to 12/2020 as the COVID-19 pandemic response period. We reviewed electronic medical records and extracted sociodemographic information, medical history, and follow-up and treatment data to define steps within the LTBI cascade of care. Logistic regressions were used to assess factors associated with LTBI treatment acceptance and completion, adjusted by potential confounders and COVID-19 period. Results Data from 312 patients were included. There was a significant decrease in the number of monthly LTBI referrals (median, 18 vs. 8, p=0.02) and LTBI evaluations (median, 17.5 vs. 7, p< 0.01) during COVID-19. There was a decrease in the proportion of immigrants as indication for LTBI testing (30% vs. 9%; p< 0.01), and an increase in LTBI diagnoses based on interferon-gamma release assay (IGRA; 30% vs. 49%; p< 0.01) during COVID-19. The proportion of people who were recommended LTBI treatment was similar before and during COVID-19 (76% vs. 81%, p=0.41), as well as the LTBI treatment acceptance rates (56% vs. 64%, p=0.28), and LTBI treatment completion rates (65% vs. 63%, p=0.85). In multivariate analysis, LTBI treatment acceptance was associated with Hispanic ethnicity, younger age, male sex, IGRA use, no comorbidities, and non-healthcare occupation, independent of COVID-19 period. LTBI treatment completion was associated with taking a rifamycin-containing regimen, independent of COVID-19 period. Conclusion We observed a significant decline in the number of monthly LTBI referrals and evaluations during COVID-19. Our findings indicate an unintended negative impact of the COVID-19 response in LTBI screening efforts in our region. LTBI treatment acceptance and completion rates were not affected during COVID-19. Disclosures All Authors: No reported disclosures

Identifying factors affecting latent tuberculosis treatment acceptance among healthcare workers: a retrospective analysis in a tertiary care centre

ObjectiveOfficial guidelines recommend tuberculosis (TB) screening programmes for all healthcare workers (HCWs), along with offering treatment when latent TB infection (LTBI) is diagnosed. However, adherence to treatment among HCWs is lower compared with non-HCWs. The aim of the present study was to examine the rate of LTBI treatment acceptance among HCWs and to characterise the factors associated with non-acceptance.Design and settingThis was a retrospective cohort study. All HCWs diagnosed with LTBI, who had tuberculin skin test (TST) conversion during their work, between 2000 and 2015, in a single tertiary academic medical centre, and who consented to answer a questionnaire, were enrolled.ResultsOverall, 147 of 219 (67%) with TST conversion agreed to participate. Acceptance rate for LTBI treatment was only 16%. The overall completion rate among those who accepted treatment was 87%. HCWs’ recall of discussing the importance of LTBI treatment with their caregiver had the strongest association with LTBI treatment acceptance: 23 of 52 HCWs (44%) who recalled this discussion accepted treatment (adjusted OR=10.2, 95% CI: 2.2 to 47.6, p=0.003). Knowing the risk of developing TB was associated with 3.7 increased odds to accept treatment (95% CI: 1.2 to 11.8, p=0.02).ConclusionsLTBI acceptance rate was very low among our HCWs. Focusing on educating HCWs is potentially the key step towards an increased rate of LTBI treatment acceptance.

Understanding Mechanisms Behind Discrimination Using Diffusion Decision Modeling

Past research has documented where discrimination occurs or tested interventions that reduce discrimination. Less is known about how discriminatory behavior emerges and the mechanisms through which successful interventions work. Two studies (N > 4500) apply the Diffusion Decision Model (DDM) to the Judgment Bias Task, a measure of discrimination. In control conditions, participants gave preferential treatment (acceptance to a hypothetical honor society) to physically attractive applicants. DDM analyses revealed participants initially favored attractive candidates and attractiveness was accumulated as evidence of being qualified. Two interventions—raising awareness of bias and asking for more deliberative judgments—reduced discrimination through separate mechanisms. Raising awareness reduced biases in drift rates while increasing deliberation raised decision thresholds. This work offers insight into how discrimination emerges and may aid efforts to develop interventions to lessen discrimination.

Determinants of Latent Tuberculosis Treatment Acceptance and Completion in Healthcare Personnel

Background US public health strategy for eliminating tuberculosis (TB) prioritizes treatment of latent TB infection (LTBI). Healthcare personnel (HCP) are less willing to accept treatment than other populations. Little is known about factors associated with HCP LTBI therapy acceptance and completion. Methods We conducted a retrospective chart review to identify all employees with LTBI at time of hire at a large academic medical center during a 10-year period. Personal demographics, occupational factors, and clinic visit variables were correlated with LTBI treatment acceptance and completion rates using multivariate logistic regression. Results Of 470 HCP with LTBI for whom treatment was recommended, 193 (41.1%) accepted treatment, while 137 (29.1%) completed treatment. Treatment adherence was better with 4 months of rifampin than 9 months of isoniazid (95% vs 68%, P < .005). Increased age of the healthcare worker was independently associated with lower rates of treatment acceptance (odds ratio [95% confidence interval]: 0.97 [0.94–0.99] per year), as was having an occupation of clinician (0.47 [0.26–0.85]) or researcher (0.34 [0.19–0.64]). Male gender was associated with higher treatment acceptance (1.90 [1.21–2.99]). Treatment completion was associated with being from a low- (9.49 [2.06–43.73]) or medium- (8.51 [3.93–18.44]) TB-burden country. Conclusions Geographic and occupational factors affect acceptance and completion of LTBI therapy. Short-course regimens may improve adherence. Physicians, researchers, and HCP from high-TB-burden countries have lower treatment rates than other HCP. Improving LTBI treatment in HCP will require attending to cultural and occupational differences.

Impact of Choice of Test for Latent Tuberculosis Infection on Treatment Acceptance and Completion

Objective: The aim of this study is to assess whether choice of test for tuberculosis (TB) infection affects decisions to accept and complete treatment among contacts to TB cases. Methods: Retrospective study is conducted in which TB contacts, ⩾15 years old during 2005 and 2009, were tested for infection with either a tuberculin skin test (TST) or an interferon-gamma release assay test, the QuantiFERON-TB Gold In-Tube (QFT-GIT). Results: Of 658 persons with valid test results, 185 (28%) had positive results, including 128 of 406 (32%) who had TST and 57 of 252 (23%) who received QFT-GIT. Treatment acceptance was 43 of 57 (75%) among QFT-GIT-positive and 97 of 128 (76%) among TST-positive persons (risk ratio [RR] = 1.0, 95% confidence interval [CI], 0.83-1.2). Treatment completion was 56% among QFT-GIT-positive (32 of 57) and 59% (75 of 128) among TST-positive persons (RR = 0.96, 95% CI, 0.73-1.26). Discussion: Our study showed no difference in proportions of TB contacts ⩾15 years old with positive TST results who accepted or completed LTBI treatment compared with those with positive QFT-GIT results. Future studies should include high-risk persons with no known TB exposure, who constitute the main reservoir for TB cases in the United States.