TB or Not TB: Treatment of Latent Tuberculosis Infection in Harlem, New York

An estimated 9 to 14 million persons in the United States have latent tuberculosis infection (LTBI) and are therefore at risk for progression to active disease. Diagnosis and treatment for LTBI has been identified by the Centers for Disease Control and Prevention (CDC) and the Institute of Medicine as a major strategy for elimination of tuberculosis (TB) in the U.S. Approximately 200,000 - 300,000 Americans are treated for LTBI each year. This dissertation investigates patient characteristics that are associated with LTBI treatment completion and assesses the impact of a peer-based experimental intervention on adherence to, and completion of, LTBI treatment. A review of the literature (Chapter 2) demonstrates that LTBI treatment completion rates in the U.S. and Canada generally fall below established targets and have been reported to range from 20 to 65% for a 6-month course of self-administered treatment. Associations between patient factors, clinic facilities, or treatment characteristics and adherence to LTBI treatment were found to be inconsistent across studies. Additionally, adherence interventions have been developed but no single intervention has shown consistent effectiveness. This suggests that a 'one-size-fits-all' approach to LTBI treatment adherence is not likely to succeed across all settings. The remainder of the dissertation focuses on predictors of LTBI treatment completion and the impact of a peer-based experimental intervention on adherence to, and completion of, LTBI treatment in two separate randomized controlled trials. Data for these analyses are drawn from two sequential randomized controlled trials designed to compare a peer-based intervention to usual care for ensuring completion of treatment for LTBI in an urban clinic setting: the Pathways to Completion Study (recruitment from 1996 through 2000) as well as from the Tuberculosis Adherence Partnership Alliance Study (TAPAS ) (recruitment from 2002 through 2005). Chapter 3 describes the change in demographic, social, and behavioral characteristics between the two study populations. The first analysis (Chapter 4) examines predictors of LTBI treatment completion in this population. Our results suggest that foreign birth, homelessness, marriage, and alcohol or drug use all influence completion of TLTBI through complex interactions. Overall, married persons had better completion rates, but married foreign-born patients were substantially more likely to complete therapy than unmarried foreign-born patients. Similarly, alcohol users were less likely to complete therapy, but homeless alcohol users were more likely to complete treatment than other homeless patients. The latter is probably an artifact of our clinic population, which includes patients from alcohol and substance abuse rehabilitation programs. Residence in such programs may have a positive effect on treatment completion. Race/ethnicity did not appear to be associated with treatment completion, although the differences between the two study populations made this difficult to assess. Following from this, an analysis of the effectiveness of a peer-based experimental intervention on adherence to, and completion of, LTBI treatment in two separate randomized controlled trials (Chapter 5) finds peer support experimental intervention to be very effective in the Pathways population but not in the TAPAS population where completion rates increased substantially for both the intervention and control groups. The power for detecting an intervention effect in TAPAS was reduced by the higher than expected completion rates in both groups; however, the effect of the TAPAS intervention is statistically significant in the adherence model. Adherence analysis in TAPAS suggests that it is important to intervene early in the treatment as the first two months of treatment present a danger period where patients tend to default treatment. The most common reasons reported for not adhering to treatment were forgot, ran out of medications, and other priorities. Identifying reasons for missing medications can suggest possible foci for interventions in the early months, such as weekly reminders to take the medications and ensuring that prescriptions are refilled on schedule. Taken together, the findings of this research have significant implications for improving adherence to and completion of LTBI treatment. Currently, the primary intervention for improving LTBI adherence consists of educational programs to increase knowledge and modify attitudes. Our findings suggest that tangible assistance would be more effective in encouraging treatment completion. Additionally, adherence analysis in TAPAS suggests that it is important to intervene early in the treatment. Close follow-up of patients during the first two months of treatment, with prompt intervention to encourage completion among those stopping treatment, may yield better outcomes and reduce costs over the long term

Child contact management in high tuberculosis burden countries: A mixed-methods systematic review

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. Considering the World Health Organization recommendation to implement child contact management (CCM) for TB, we conducted a mixed-methods systematic review to summarize CCM implementation, challenges, predictors, and recommendations. We searched the electronic databases of PubMed/MEDLINE, Scopus, and Web of Science for studies published between 1996–2017 that reported CCM data from high TB-burden countries. Protocol details for this systematic review were registered on PROSPERO: International prospective register of systematic reviews (#CRD42016038105). We formulated a search strategy to identify all available studies, published in English that specifically targeted a) population: child contacts (<15 years) exposed to TB in the household from programmatic settings in high burden countries (HBCs), b) interventions: CCM strategies implemented within the CCM cascade, c) comparisons: CCM strategies studied and compared in HBCs, and d) outcomes: monitoring and evaluation of CCM outcomes reported in the literature for each CCM cascade step. We included any quantitative, qualitative, mixed-methods study design except for randomized-controlled trials, editorials or commentaries. Thirty-seven studies were reviewed. Child contact losses varied greatly for screening, isoniazid preventive therapy initiation, and completion. CCM challenges included: infrastructure, knowledge, attitudes, stigma, access, competing priorities, and treatment. CCM recommendations included: health system strengthening, health education, and improved preventive therapy. Identified predictors included: index case and clinic characteristics, perceptions of barriers and risk, costs, and treatment characteristics. CCM lacks standardization resulting in common challenges and losses throughout the CCM cascade. Prioritization of a CCM-friendly healthcare environment with improved CCM processes and tools; health education; and active, evidence-based strategies can decrease barriers. A focused approach toward every aspect of the CCM cascade will likely diminish losses throughout the CCM cascade and ultimately decrease TB related morbidity and mortality in children

The START Study to evaluate the effectiveness of a combination intervention package to enhance antiretroviral therapy uptake and retention during TB treatment...

Background: Initiating antiretroviral therapy (ART) early during tuberculosis (TB) treatment increases survival; however, implementation is suboptimal. Implementation science studies are needed to identify interventions to address this evidence-to-program gap. Objective: The Start TB Patients on ART and Retain on Treatment (START) Study is a mixed-methods, cluster-randomized trial aimed at evaluating the effectiveness, cost-effectiveness, and acceptability of a combination intervention package (CIP) to improve early ART initiation, retention, and TB treatment success among TB/HIV patients in Berea District, Lesotho. Design: Twelve health facilities were randomized to receive the CIP or standard of care after stratification by facility type (hospital or health center). The CIP includes nurse training and mentorship, using a clinical algorithm; transport reimbursement and health education by village health workers (VHW) for patients and treatment supporters; and adherence support using text messaging and VHW. Routine data were abstracted for all newly registered TB/HIV patients; anticipated sample size was 1,200 individuals. A measurement cohort of TB/HIV patients initiating ART was recruited; the target enrollment was 384 individuals, each to be followed for the duration of TB treatment (6–9 months). Inclusion criteria were HIV-infected; on TB treatment; initiated ART within 2 months of TB treatment initiation; age ≥18; English- or Sesotho-speaking; and capable of informed consent. The exclusion criterion was multidrug-resistant TB. Three groups of key informants were recruited from intervention clinics: early ART initiators; non/late ART initiators; and health care workers. Primary outcomes include ART initiation, retention, and TB treatment success. Secondary outcomes include time to ART initiation, adherence, change in CD4+ count, sputum smear conversion, cost-effectiveness, and acceptability. Follow-up and data abstraction are complete. Discussion: The START Study evaluates a CIP targeting barriers to early ART implementation among TB/HIV patients. If the CIP is found effective and acceptable, this study has the potential to inform care for TB/HIV patients in high-burden, resource-limited countries in sub-Saharan Africa. Keywords: TB/HIV integration; implementation science; cost-effectiveness; acceptability; TB treatment succes

Limited awareness of pre-exposure prophylaxis among black men who have sex with men and transgender women in New York City

Awareness of Pre-exposure prophylaxis (PrEP) was assessed among a cohort of substance-using black men who have sex with men and transgender women (MSM/TGW) participating in the STAR Study, which recruited black MSM/TGW in New York City for HIV testing and linked HIV-infected individuals into care from July 2012 to April 2015. Sociodemographic, psychosocial, known HIV risk factors, and PrEP awareness were assessed among participants. Multivariable logistic regression was conducted to assess factors associated with PrEP awareness. Of 1673 participants, median age was 43 years and 25% were under age 30. Most participants (85.8%) reported having insufficient income for basic necessities at least occasionally, 54.8% were homeless, and 71.3% were unemployed. Awareness of PrEP was reported among 18.2% of participants. PrEP awareness was associated with younger age (adjusted odds ratio [aOR] 0.87, per 5 years), gay identity (aOR 2.46), higher education (aOR 1.70), more frequent past HIV testing (aOR 3.18), less HIV stigma (aOR 0.61), less hazardous/harmful alcohol use (aOR 0.61), and more sexual partners (aOR 1.04, per additional partner in past 30 days). In this substance-using black MSM/TGW cohort with high rates of poverty and homelessness, PrEP awareness was low. This study demonstrates the need for targeted dissemination of PrEP information to key populations to increase awareness and ultimately improve uptake and utilization of PrEP

The PREVENT study to evaluate the effectiveness and acceptability of a community-based intervention to prevent childhood tuberculosis in Lesotho: study protocol for a cluster randomized controlled trial

Background Effective, evidence-based interventions to prevent childhood tuberculosis (TB) in high TB/HIV-burden, resource-limited settings are urgently needed. There is limited implementation of evidence-based contact management strategies, including isoniazid preventive therapy (IPT), for child contacts of TB cases in Lesotho. Methods/design This mixed-methods implementation science study utilizes a two-arm cluster-randomized trial design with randomization at the health facility level. The study aims to evaluate the effectiveness and acceptability of a combination community-based intervention (CBI) versus standard of care (SOC) for the management of child TB contacts. The study includes three phases: (I) exploratory phase; (II) intervention implementation and testing phase; (III) post-intervention explanatory phase. Healthcare provider interviews to inform intervention refinement (phase I) were completed in December 2015. In phase II, 10 health facilities were randomized to deliver the CBI or SOC, with stratification by facility type (i.e., hospital vs. health center). CBI holistically addresses the complex provider-related, patient-related, and caregiver-related barriers to prevention of childhood TB through nurse training and mentorship; health education for caregivers and patients by village health workers; adherence support using text messaging and village health workers; and multidisciplinary team meetings, where programmatic data are reviewed and challenges and solutions are discussed. SOC sites follow country guidelines for child TB contact management. Routine TB program data will be abstracted for all adult TB cases newly registered during the study period and their child contacts from TB registers and cards. The anticipated sample size is 1080 child contacts. Primary outcomes are yield (number) of child contacts, including children < 5 years of age and HIV-positive children < 15 years of age; IPT initiation; and IPT completion. Secondary outcomes include HIV testing; yield of active prevalent TB among child contacts; and acceptability and utilization of CBI components. Intervention implementation began in February 2016 and is ongoing. Post-intervention interviews with healthcare providers and caregivers (phase III) commenced in February 2017. Discussion The PREVENT study tests the effectiveness and acceptability of a novel combination CBI for child TB contact management in Lesotho. If effective, CBI will have important implications for addressing childhood TB in Lesotho and elsewhere. Trial registration ClinicalTrials.gov, NCT02662829 . Registered on 15 January 2016

Using mHealth for HIV/TB treatment support in Lesotho : enhancing patient–provider communication in the START study.

CAPRISA, 2017.Abstract available in pdf

Provider attitudes about childhood tuberculosis prevention in Lesotho : a qualitative study

CITATION: Hirsch-Moverman, Y. , et al. 2020. Provider attitudes about childhood tuberculosis prevention in Lesotho : a qualitative study. BMC Health Services Research, 20:461, doi:10.1186/s12913-020-05324-0.The original publication is available at https://bmchealthservres.biomedcentral.comBackground: The World Health Organization estimated that 1.12 million children developed tuberculosis (TB) in 2018, and at least 200,000 children died from TB. Implementation of effective child contact management is an important strategy to prevent childhood TB but these practices often are not prioritized or implemented, particularly in low- and middle-income countries. This study aimed to explore attitudes of healthcare providers toward TB prevention and perceived facilitators and challenges to child contact management in Lesotho, a high TB burden country. Qualitative data were collected via group and individual in-depth interviews with 12 healthcare providers at five health facilities in one district and analyzed using a thematic framework. Results: Healthcare providers in our study were interested and committed to improve child TB contact management and identified facilitators and challenges to a successful childhood TB prevention program. Facilitators included: provider understanding of the importance of TB prevention and enhanced provider training on child TB contact management, with a particular focus on ruling out TB in children and addressing side effects. Challenges identified by providers were at multiple levels -- structural, clinic, and individual and included: [1] access to care, [2] supply-chain issues, [3] identification and screening of child contacts, and [4] adherence to isoniazid preventive therapy. Conclusions: Given the significant burden of TB morbidity and mortality in young children and the recent requirement by the WHO to report IPT initiation in child contacts, prioritization of child TB contact management is imperative and should include enhanced provider training on childhood TB and mentorship as well as strategies to eliminate challenges. Strategies that enable more efficient child TB contact management delivery include creating standardized tools that facilitate the implementation, tracking, and monitoring of child TB contact management coupled with guidance and mentorship from the district health management team. To tackle access to care challenges, we propose delivering intensive community health education, conducting community screening more efficiently using standardized tools, and facilitating access to services in the community.https://bmchealthservres.biomedcentral.com/articles/10.1186/s12913-020-05324-0Publisher's versio

Paediatric tuberculosis preventive treatment preferences among HIV-positive children, caregivers and healthcare providers in Eswatini: a discrete choice experiment.

HEARD, 2021.Objective: Isoniazid preventive therapy initiation and completion rates are suboptimal among children. Shorter tuberculosis (TB) preventive treatment (TPT) regimens have demonstrated safety and efficacy in children and may improve adherence but are not widely used in high TB burden countries. Understanding preferences regarding TPT regimens’ characteristics and service delivery models is key to designing services to improve TPT initiation and completion rates. We examined paediatric TPT preferences in Eswatini, a high TB burden country. Design: We conducted a sequential mixed-methods study utilising qualitative methods to inform the design of a discrete choice experiment (DCE) among HIV-positive children, caregivers and healthcare providers (HCP). Drug regimen and service delivery characteristics included pill size and formulation, dosing frequency, medication taste, treatment duration and visit frequency, visit cost, clinic wait time, and clinic operating hours. An unlabelled, binary choice design was used; data were analysed using fixed and mixed effects logistic regression models, with stratified models for children, caregivers and HCP. Setting: The study was conducted in 20 healthcare facilities providing TB/HIV care in Manzini, Eswatini, from November 2018 to December 2019. Participants: Ninety-one stakeholders completed in-depth interviews to inform the DCE design; 150 children 10–14 years, 150 caregivers and 150 HCP completed the DCE. Results: Despite some heterogeneity, the results were fairly consistent among participants, with palatability of medications viewed as the most important TPT attribute; fewer and smaller pills were also preferred. Additionally, shorter waiting times and cost of visit were found to be significant drivers of choices. Conclusion: Palatable medication, smaller/fewer pills, low visit costs and shorter clinic wait times are important factors when designing TPT services for children and should be considered as new paediatric TPT regimens in Eswatini are rolled out. More research is needed to determine the extent to which preferences drive TPT initiation, adherence and completion rates

Sex, PrEP, and Stigma: Experiences with HIV Pre-exposure Prophylaxis Among New York City MSM Participating in the HPTN 067/ADAPT Study

The HPTN 067/Alternative Dosing to Augment Pre-Exposure Prophylaxis Pill Taking (ADAPT) study evaluated daily and non-daily dosing schedules for oral pre-exposure prophylaxis (PrEP) to prevent HIV. A qualitative sub-study including focus groups and in-depth interviews was conducted among men who have sex with men participating in New York City to understand their experience with PrEP and study dosing schedules. The 37 sub-study participants were 68% black, 11% white, and 8% Asian; 27% were of Hispanic/Latino ethnicity. Mean age was 34 years. Themes resulting from qualitative analysis include: PrEP is a significant advance for HIV prevention; non-daily dosing of PrEP is congruent with HIV risk; and pervasive stigma connected to HIV and risk behavior is a barrier to PrEP adherence, especially for non-daily dosing schedules. The findings underscore how PrEP intersects with other HIV prevention practices and highlight the need to understand and address multidimensional stigma related to PrEP use

Daily and Nondaily Oral Preexposure Prophylaxis in Men and Transgender Women Who Have Sex With Men: The Human Immunodeficiency Virus Prevention Trials Network 067/ADAPT Study

Background: Nondaily dosing of oral preexposure prophylaxis (PrEP) may provide equivalent coverage of sex events compared with daily dosing. Methods: At-risk men and transgender women who have sex with men were randomly assigned to 1 of 3 dosing regimens: 1 tablet daily, 1 tablet twice weekly with a postsex dose (time-driven), or 1 tablet before and after sex (event-driven), and were followed for coverage of sex events with pre- and postsex dosing measured by weekly self-report, drug concentrations, and electronic drug monitoring. Results: From July 2012 to May 2014, 357 participants were randomized. In Bangkok, the coverage of sex events was 85% for the daily arm compared with 84% for the time-driven arm (P = .79) and 74% for the event-driven arm (P = .02). In Harlem, coverage was 66%, 47% (P = .01), and 52% (P = .01) for these groups. In Bangkok, PrEP medication concentrations in blood were consistent with use of ≥2 tablets per week in >95% of visits when sex was reported in the prior week, while in Harlem, such medication concentrations occurred in 48.5% in the daily arm, 30.9% in the time-driven arm, and 16.7% in the event-driven arm (P < .0001). Creatinine elevations were more common in the daily arm (P = .050), although they were not dose limiting. Conclusions: Daily dosing recommendations increased coverage and protective drug concentrations in the Harlem cohort, while daily and nondaily regimens led to comparably favorable outcomes in Bangkok, where participants had higher levels of education and employment