Tuberculosis preventive treatment uptake among adults living with human immunodeficiency virus: Analysis of Zimbabwe population-based human immunodeficiency virus impact assessment 2020.

BACKGROUND: Tuberculosis remains the leading cause of death by an infectious disease among people living with HIV (PLHIV). TB Preventive Treatment (TPT) is a cost-effective intervention known to reduce morbidity and mortality. We used data from ZIMPHIA 2020 to assess TPT uptake and factors associated with its use. METHODOLOGY: ZIMPHIA a cross-sectional household survey, estimated HIV treatment outcomes among PLHIV aged ≥15 years. Randomly selected participants provided demographic and clinical information. We applied multivariable logistic regression models using survey weights. Variances were estimated via the Jackknife series to determine factors associated with TPT uptake. RESULTS: The sample of 2419 PLHIV ≥15 years had 65% females, 44% had no primary education, and 29% lived in urban centers. Overall, 38% had ever taken TPT, including 15% currently taking TPT. Controlling for other variables, those screened for TB at last HIV-related visit, those who visited a TB clinic in the previous 12 months, and those who had HIV viral load suppression were more likely to take TPT. CONCLUSION: The findings show suboptimal TPT coverage among PLHIV. There is a need for targeted interventions and policies to address the barriers to TPT uptake, to reduce TB morbidity and mortality among PLHIV.

Situation Analysis of Early Implementation of Programmatic Management of Tuberculosis Preventive Treatment among Household Contacts of Pulmonary TB Patients in Delhi, India.

Tuberculosis Preventive Treatment (TPT) is a powerful tool for preventing the TB infection from developing into active TB disease, and has recently been expanded to all household contacts of TB cases in India. This study employs a mixed-methods approach to conduct a situational analysis of the initial phase of TPT implementation among household contacts of pulmonary TB patients in three districts of Delhi, India. It was completed using a checklist based assessments, care cascade data, and qualitative analysis. Our observations indicated that organizational structure and planning were established, but implementation of TPT was suboptimal with issues in drug availability and procurement, budget, human resources, and training. Awareness and motivation, and shorter regimen, telephonic assessment, and collaboration with NGOs emerged as enablers. Apprehension about taking TPT, erratic drug supply, long duration of treatment, side effects, overburden, large population, INH resistance, data entry issues, and private provider reluctance emerged as barriers. The study revealed potential solutions for optimizing TPT implementation. It is evident that, while progress has been made in TPT implementation, there is room for improvement and refinement across various domains.

Outcomes and Challenges in the Programmatic Implementation of Tuberculosis Preventive Therapy among Household Contacts of Pulmonary TB Patients: A Mixed-Methods Study from a Rural District of Karnataka, India.

The National TB Elimination Programme (NTEP) of India is implementing tuberculosis preventive treatment (TPT) for all household contacts (HHCs) of pulmonary tuberculosis patients (index patients) aged <5 years and those HHCs aged >5 years with TB infection (TBI). We conducted an explanatory mixed-methods study among index patients registered in the Kolar district, Karnataka during April-December 2022, to assess the TPT cascade and explore the early implementation challenges for TPT provision. Of the 301 index patients, contact tracing home visits were made in 247 (82.1%) instances; a major challenge was index patients' resistance to home visits fearing stigma, especially among those receiving care from the private sector. Of the 838 HHCs, 765 (91.3%) were screened for TB; the challenges included a lack of clarity on HHC definition and the non-availability of HHCs during house visits. Only 400 (57.8%) of the 692 eligible HHCs underwent an IGRA test for TBI; the challenges included a shortage of IGRA testing logistics and the perceived low risk among HHCs. As HHCs were unaware of their IGRA results, a number of HHCs actually eligible for TPT could not be determined. Among the 83 HHCs advised of the TPT, 81 (98%) initiated treatment, of whom 63 (77%) completed treatment. Though TPT initiation and completion rates are appreciable, the NTEP needs to urgently address the challenges in contact identification and IGRA testing.

Isoniazid Preventive Therapy Uptake and Its Effect on Tuberculosis Incidence Among People Living with HIV in Illubabor and Buno Bedelle Zones, South-West Ethiopia, 2022: A Retrospective Cohort Study.

Introduction: Tuberculosis (TB) remains the leading cause of death among human immune deficiency virus (HIV) patients. Based on the 2020 global TB report, Ethiopia was among the 30 high TB and TB/HIV burden countries. This study filled gaps regarding IPT uptake in the study area and representative sample determination for assessing TB incidence and its predictors at public health facilities in Illubabor and Buno Bedelle zones, south-west Ethiopia. Methods: This retrospective cohort study was conducted among people living with HIV (PLHIV) who were on antiretroviral therapy (ART) at public health facilities in Illubabor and Buno Bedelle zones, south-west Ethiopia. Both isoniazid preventive therapy (IPT) exposed and unexposed PLHIV were followed from the date of ART initiation until the date of TB diagnosis of the most recent visit prior to the end of follow-up. The Cox proportional hazard model was employed to identify variables that predicted the incidence of TB at a P value of <0.05. Results: Data were collected on 421 PLHIV, with a response rate of 97.4%. The median (interquartile range (IQR)) age of the study participants was 32 (28-40) year. The incidence rate of pulmonary TB was 3.1 per 1000 person-months (95% CI: 2.4-3.9). The incidence rate of TB among IPT-exposed PLHIV was 1.45 per 1000 person-months, but it was 6.2 per 1000 person-months in the unexposed group. Patient's residence, IPT exposure, baseline ART adherence, baseline hemoglobin level, baseline CD4+ cell, recent hemoglobin level, recent CD4+ cell, recent BMI, and recent WHO HIV clinical stage were independently associated with the incidence of TB. Conclusion: Healthcare professionals working in ART clinics should routinely assess HIV-positive individuals for changes in clinical indicators and environmental exposures like living conditions, which will help HIV-positive individuals in reducing their risk for TB. Likewise, patients attending ART clinics should receive counseling on a regular basis.

Contact Tracing and Tuberculosis Preventive Therapy for Household Child Contacts of Pulmonary Tuberculosis Patients in the Kyrgyz Republic: How Well Are We Doing?

Early identification, screening and investigation for tuberculosis (TB), and provision of TB preventive therapy (TPT), reduces risk of TB among child household contacts of pulmonary TB patients (index patients). A cohort study was conducted to describe the care cascade and timeliness of contact tracing and TPT initiation among child household contacts (aged < 15 years) of index patients initiated on TB treatment in Bishkek, the Kyrgyz Republic during October 2021-September 2022. In the register, information on the number of child household contacts was available for 153 (18%) of 873 index patients. Of 297 child household contacts identified, data were available for 285, of whom 261 (92%) were screened for TB. More than 50% were screened after 1 month of the index patient initiating TB treatment. TB was diagnosed in 23/285 (9%, 95% CI: 6-13%) children. Of 238 TB-free children, 130 (55%) were eligible for TPT. Of the latter, 64 (49%) were initiated on TPT, of whom 52 (81%) completed TPT. While TPT completion was excellent, there was deficiency in contact identification, timely screening and TPT initiation. Thus, healthcare providers should diligently request and record details of child household contacts, adhere to contact tracing timelines and counsel caregivers regarding TPT.

Barriers and Facilitators of Isoniazid Preventive Therapy Implementation among People Living with HIV in Nigeria: A Scoping Review of the Literature.

BACKGROUND: Implementation of Isoniazid Preventive Therapy (IPT) among People Living with HIV (PLHIV) continues to be a significant challenge, and there is a shortage of effective interventions. This scoping review aimed to determine barriers and facilitators of IPT implementation including its uptake and completion among PLHIV in Nigeria. METHODS: PubMed, Medline Ovid, Scopus, Google scholar, web of science and Cochrane Library were searched for articles published between January 2019 to June 2022 that addressed barriers and facilitators of IPT uptake and completion in Nigeria. The study used the PRISMA checklist to ensure the quality of the study. RESULTS: The initial search revealed 780 studies, of which 15 studies were finally included in the scoping review. The authors inductively organized IPT barriers among PLHIV into patients-, health system-,programmatic- and provider-related barriers. Facilitators of IPT were sub-categorized into programmatic (Monitoring and Evaluation or logistic), patient-related and provider-related (capacity building) and health systems sub-categories. Most studies highlighted more barriers than facilitators, and across all studies, IPT uptake was 3% - 61.2% while IPT completion was 40 - 87.9% but these figures are higher in quality improvement studies. CONCLUSION: Identified barriers include health system, and programmatic-across, and in all the studies, IPT uptake was 3%-61.2%. Cost-effective and locally developed interventions addressing context-specific barriers should be developed to address patient, provider, programmatic, and health systems-specific findings in our study with a clear understanding that there may be other barriers limiting uptake and completion of IPT at the level of community and caregivers.

CONTEXTE: CONTEXTE: La mise en œuvre du traitement préventif à l'isoniazide (TPI) chez les personnes vivant avec le VIH (PVVIH) reste un défi de taille, et il y a une pénurie d'interventions efficaces. Cette étude exploratoire visait à déterminer les obstacles et les facilitateurs de la mise en œuvre du TPI, y compris son adoption et son achèvement parmi les personnes vivant avec le VIH au Nigéria. MÉTHODES: PubMed, Medline Ovid, Scopus, Google scholar, web of science et Cochrane Library ont été recherchés pour les articles publiés entre janvier 2019 et juin 2022 qui traitaient des obstacles et des facilitateurs de l'adoption et de l'achèvement du TPI au Nigéria. L'étude a utilisé la liste de contrôle PRISMA pour garantir la qualité de l'étude. RÉSULTATS: La recherche initiale a révélé 780 études, dont 15 ont finalement été incluses dans l'examen de la portée. Les auteurs ont organisé de manière inductive les obstacles au TPI chez les PVVIH en barrières liées aux patients, aux systèmes de santé, aux programmes et aux prestataires. Les facilitateurs du TPI ont été subdivisés en souscatégories liées aux programmes (suivi et évaluation ou logistique), aux patients et aux prestataires (renforcement des capacités) et aux systèmes de santé. La plupart des études ont mis en évidence plus d'obstacles que de facilitateurs et, dans l'ensemble des études, le taux d'utilisation du TPI était compris entre 3 % et 61,2 %, tandis que le taux d'achèvement du TPI était compris entre 40 % et 87,9 %, mais ces chiffres sont plus élevés dans les études d'amélioration de la qualité. CONCLUSION: Les obstacles identifiés sont liés au système de santé et aux programmes, et dans toutes les études, le taux d'utilisation du TPI était compris entre 3 % et 61,2 %. Des interventions rentables et développées localement pour faire face aux obstacles spécifiques au contexte devraient être mises au point pour répondre aux conclusions de notre étude concernant les patients, les prestataires, les programmes et les systèmes de santé, tout en sachant qu'il peut y avoir d'autres obstacles qui limitent l'adoption et l'achèvement de l'IPT au niveau de la communauté et des soignants. Mots-clés: Thérapie préventive à l'isoniazide; Personnes vivant avec le VIH; Obstacles; Facilitateurs; Adoption; Achèvement.

Effect of pregnancy versus postpartum maternal isoniazid preventive therapy on infant growth in HIV-exposed uninfected infants: a post-hoc analysis of the TB APPRISE trial.

Background: Isoniazid preventive therapy (IPT) initiation during pregnancy was associated with increased incidence of adverse pregnancy outcomes in the TB APPRISE trial. Effects of in utero IPT exposure on infant growth are unknown. Methods: This post-hoc analysis used data from the TB APPRISE trial, a multicentre, double-blind, placebo-controlled trial, which randomised women to 28-week IPT starting in pregnancy (pregnancy-IPT) or postpartum week 12 (postpartum-IPT) in eight countries with high tuberculosis prevalence. Participants were enrolled between August 2014 and April 2016. Based on modified intent-to-treat analyses, we analysed only live-born babies who had at least one follow-up after birth and compared time to infant growth faltering between arms to 12 weeks and 48 weeks postpartum in overall and sex-stratified multivariable Cox proportional hazards regression. Factors adjusted in the final models include sex of infant, mother's baseline BMI, age in years, ART regimen, viral load, CD4 count, education, and household food insecurity. Results: Among 898 HIV-exposed uninfected (HEU) infants, 447 (49.8%) were females. Infants in pregnancy-IPT had a 1.47-fold higher risk of becoming underweight by 12 weeks (aHR 1.47 [95% CI: 1.06, 2.03]) than infants in the postpartum-IPT; increased risk persisted to 48 weeks postpartum (aHR 1.34 [95% CI: 1.01, 1.78]). Maternal IPT timing was not associated with stunting or wasting. In sex-stratified analyses, male infants in the pregnancy-IPT arm experienced an increased risk of low birth weight (LBW) (aRR 2.04 [95% CI: 1.16, 3.68), preterm birth (aRR 1.81 [95% CI: 1.04, 3.21]) and becoming underweight by 12 weeks (aHR 2.02 [95% CI: 1.29, 3.18]) and 48 weeks (aHR 1.82 [95% CI: 1.23, 2.69]). Maternal IPT timing did not influence growth in female infants. Interpretation: Maternal IPT during pregnancy was associated with an increased risk of LBW, preterm birth, and becoming underweight among HEU infants, particularly male infants. These data add to prior TB APPRISE data, suggesting that IPT during pregnancy impacts infant growth, which could inform management, and warrants further examination of mechanisms. Funding: The TB APPRISE study Supported by the National Institutes of Health (NIH) (award numbers, UM1AI068632 [IMPAACT LOC], UM1AI068616 [IMPAACT SDMC], and UM1AI106716 [IMPAACT LC]) through the National Institute of Allergy and Infectious Diseases, with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract number, HHSN275201800001I) and the National Institute of Mental Health.

Prevalence of neurotoxicity symptoms among postpartum women on isoniazid preventive therapy and efavirenz-based treatment for HIV: an exploratory objective of the IMPAACT P1078 randomized trial.

BACKGROUND: This exploratory analysis investigates the prevalence and risk factors of neurocognitive toxicity in postpartum women on HIV treatment in response to a concern of an Isoniazid Preventive Therapy (IPT)/Efavirenz interaction. TRIAL DESIGN: Pregnant women on HIV treatment from countries with high TB prevalence were randomized in IMPAACT P1078 to 28 weeks of IPT started either during pregnancy or at 12 weeks postpartum. Partway through study implementation, the Patient Health Questionnaire 9, the cognitive complaint questionnaire, and the Pittsburg Sleep Quality Index were added to evaluate depression, cognitive function, and sleep quality at postpartum weeks. Screening for peripheral neuropathy was conducted throughout the study. METHODS: We summarized percentages of women with depression symptoms, cognitive dysfunction, poor sleep quality and peripheral neuropathy and assessed the association of 11 baseline risk factors of neurotoxicity using logistic regression, adjusted for gestational age stratum. RESULTS: Of 956 women enrolled, 749 (78%) had at least one neurocognitive evaluation. During the postpartum period, the percentage of women reporting at least mild depression symptoms, cognitive complaint and poor sleep quality peaked at 13%, 8% and 10%, respectively, at 12 weeks, and the percentage of women reporting peripheral neuropathy peaked at 13% at 24 weeks. There was no evidence of study arm differences in odds of all four neurotoxic symptoms. CONCLUSIONS: Timing of IPT initiation and EFV use were not associated with symptoms of neurotoxicity. Further study is advised to formally assess risk factors of neurotoxicity.

Agreement Between Measures of Adherence to Isoniazid Preventive Therapy Among People With HIV in Uganda.

Background: Isoniazid (INH) preventative therapy is recommended for people with HIV (PWH) in resource-constrained settings. Valid measures are needed to assess adherence. We aimed to examine agreement between measures overall and by level of social desirability. Methods: PWH with latent tuberculosis (TB) were recruited in Mbarara, Uganda. Past 30-day adherence was measured by the number of days with pill bottle openings using a medication event monitoring system (MEMS) and self-reported number of days pills taken. INH concentration (INH plus acetyl INH and their ratio) in hair samples was measured. We used Bland-Altman plots to examine agreement between adherence measures and calculated the area under the receiver operating characteristics curve (AUROC) to determine if INH hair concentration predicted optimal MEMS-measured adherence (≥90%). Results: A total of 301 participants enrolled; 92% were virologically suppressed, and adherence was high. The median (interquartile range [IQR]) number of pill bottle openings in 30 days was 28 (24-30) compared with 30 (28-30) via self-report. The median INH concentration (IQR) was 36.2 (17.2-62.4), and the INH:acetyl ratio was 2.43 (0.99-3.92). Agreement between self-reported and MEMS adherence was greater at more optimal adherence levels. INH:acetyl INH ratio was not predictive of optimal adherence according to MEMS (AUROC, 0.62; 95% CI, 0.52-0.72) in a subset (n = 161). Conclusions: Lower MEMS adherence levels compared with self-report suggest the need for objective adherence measures. Biologic measures have potential, although in this study INH concentration was not predictive of MEMS measured adherence. More data are needed to assess the accuracy of biologic measures.

Assessment of contextual factors shaping delivery and uptake of isoniazid preventive therapy among people living with HIV in Dar es salaam, Tanzania.

BACKGROUND: Tuberculosis has remained a leading cause of death among people living with HIV (PLHIV) globally. Isoniazid preventive therapy (IPT) is the recommended strategy by the World Health Organization to prevent TB disease and related deaths among PLHIV. However, delivery and uptake of IPT has remained suboptimal particularly in countries where HIV and TB are endemic such as Tanzania. This study sought to assess contextual factors that shape delivery and uptake of IPT in Dar es Salaam region, Tanzania. METHODOLOGY: We employed a qualitative case study design comprising of in-depth interviews with people living with HIV (n = 17), as well as key informant interviews with clinicians (n = 7) and health administrators (n = 7). We used thematic data analysis approach and reporting of the results was guided by the Consolidated Framework for Implementation Research (CFIR). RESULTS: Characteristics of IPT such as aligning the therapy to individual patient schedules and its relatively low cost facilitated its delivery and uptake. On the contrary, perceived adverse side effects negatively affected the delivery and uptake of IPT. Characteristics of individuals delivering the therapy including their knowledge, good attitudes, and commitment to meeting set targets facilitated the delivery and uptake of IPT. The process of IPT delivery comprised collective planning and collaboration among various facilities which facilitated its delivery and uptake. Organisational characteristics including communication among units and supportive leadership facilitated the delivery and uptake of IPT. External system factors including HIV stigma, negative cultural and religious values, limited funding as well as shortage of skilled healthcare workers presented as barriers to the delivery and uptake of IPT. CONCLUSION: The factors influencing the delivery and uptake of IPT among people living with HIV are multifaceted and exist at different levels of the health system. Therefore, it is imperative that IPT program implementers and policy makers adopt multilevel approaches that address the identified barriers and leverage the facilitators in delivery and uptake of IPT at both community and health system levels.

[Primary isoniazid preventive therapy : A strategy still relevant in the era of test and treat ; literature review]. / Chimioprophylaxie antituberculeuse primaire à l'isoniazide : une stratégie d'actualité à l'ère du tester et traiter ; revue de la littérature.

BACKGROUND: Tuberculosis remains a public health threat responsible as recently as 2018 for more than one million deaths. Chemoprophylaxis with isoniazid is one of the strategies implemented to control the disease. Although it is not yet widely prescribed, its utilization raises additional questions in the "test and treat" era of for anti-retroviral therapy. The objective of this study is to review the different randomized controlled trials of antitubercular Isoniazid Preventive Therapy (IPT). We have distinguished (a) "efficacy trials" (ET) comparing IPT to a placebo or the absence of chemoprophylaxis and (b) "IPT regimen trials" (RT) comparing IPT to one or several other regimens. METHODS: Literature search (keywords from published articles found in the Medline and Scopus data bases: "tuberculosis", "prophylaxis", "HIV", "randomized controlled trial") and standardized reading of selected articles reporting results from randomized trials of IPT in HIV-infected people. RESULTS: Eighteen selected trials (11 ET and 7 RT), including 19,725 participants. The regimens studied were 3H, 6H, 9H, 12H, 12H, 36H/2RZ, 3RH, 3RZ, 3RHZ, and 3HP [H: Isoniazid, R: Rifampicin, Z: Pyrazinamide, P: Rifapentine]. LOCATIONS: Ten in Africa, three in Haiti, one in India, one in the USA, one in the Americas and two multi-continental trials. In ET with or without antiretrovirals (ART), IPT significantly reduces the risk of tuberculosis, by 32 to 71%. In ET prior to ART, IPT does not appear to reduce mortality. In ET in patients receiving ART, on the other hand, IPT reduces mortality. As regards RT, there seems to be no reason to prefer other regimens to IPT. Tolerance is good. Importantly, IPT may reduce (rather than worsen) the risk of multidrug-resistant bacilli selection by decreasing the number of TB episodes and, consequently, the number of curative tuberculosis treatments. CONCLUSION: Far from becoming obsolete due to ARV treatment, IPT has remained a timely and relevant intervention.

Perspectives of Healthcare Professionals on Factors Limiting Implementation of Isoniazid Preventive Therapy in People Living with HIV in Eritrea: A Qualitative Study.

Purpose: In Eritrea, a 6-month isoniazid preventive therapy (IPT) was introduced in Eritrea in 2014 to prevent/reduce risk of incident tuberculosis in people living with HIV (PLHIV). The global and local uptake of IPT in newly enrolled PLHIV was reported to be low. Anecdotal reports showed that there was resistance from clinicians against its implementation. This study was therefore conducted to explore the factors that affect implementation of IPT in Eritrea from the perspectives of healthcare professionals. Materials and Methods: An exploratory qualitative study that used a framework content analysis using inductive approach was employed. Data were collected from a sample of HIV care clinic prescribers from regional and national referral hospitals through in-depth interviews. Senior program officers were also interviewed as key informants. A conceptual framework model was developed using a root cause analysis. Results: Overall, five themes and 13 sub-themes emerged from the in-depth interviews with healthcare professionals and key informants. Several multi-level causes/factors related to the healthcare system, HIV control program, healthcare professionals, patients and the product were identified as barriers to the implementation of IPT. Information gap on IPT and fear of isoniazid-induced liver injury were identified as the main reasons for the reluctance in administering IPT. It was observed that healthcare professionals had significant information gap that resulted in rumors and doubts on the benefits and risks of IPT, which ultimately caused reluctance on its implementation. Inadequate planning and operationalization during the introduction of IPT and inadequate laboratory setups were found to be the possible root causes for the aforementioned central problems. Conclusion: The root causes/factors for the limited implementation of IPT in Eritrea were mainly related to the HIV control program and the healthcare system. Adequate planning, operationalization and capacitation of the existing laboratory setups are recommended for a successful implementation of IPT.

An evaluation of the isoniazid preventive therapy program performance for under-fives in Kwekwe City, January 2019 - December 2020: a descriptive cross-sectional study.

Childhood tuberculosis (TB) is underserved in resource-constrained endemic areas. Zimbabwe National Tuberculosis Program recommends tuberculosis prevention treatment for children aged <5 years who are close contacts of smear-positive TB cases. The Isoniazid Preventive Therapy (IPT) program performance had never been evaluated since its inception in 2010. We therefore, assessed the IPT program's inputs, processes, outputs, and outcomes. We conducted a process evaluation using the logic model in Kwekwe City. We recruited twenty-seven health care workers from all the five municipal health facilities. Smear-positive guardians of under 5 children, health care workers, and registers were the study population. Data were collected using a questionnaire and checklists and presented as frequencies and proportions. The IPT program met requirements in provision of guidelines (10/10), screening tools (15/15) and on-the-job trainings done in all five health facilities. Isoniazid tablets supply and quarterly budgeting did not meet meeting program requirements. Fifty-nine out of 231 (25.5%) children contacts of sputum-positive TB patients were screened. Fifty-one of the 59 (86.4%) children were initiated on IPT, 42/51 (82.4%) completed the course, one developed TB, 3/51 were still on treatment and 5/51 were lost to follow up. No dropouts and deaths were recorded. Unavailability of drugs was a barrier to the IPT and negatively impacts the TB elimination program. Contact screening was the bottleneck in the successful implementation of the program. Adequate staff and provision of drugs might improve the program. We recommended the recruitment of more healthcare workers and the budget for the program.

Strategies to detect and manage latent tuberculosis infection among household contacts of pulmonary TB patients in high TB burden countries - a systematic review and meta-analysis.

OBJECTIVE: To summarise latent tuberculosis infection (LTBI) management strategies among household contacts of bacteriologically confirmed pulmonary tuberculosis (TB) patients in high-TB burden countries. METHODS: PubMed/MEDLINE (NCBI) and Scopus were searched (January 2006 to December 2021) for studies reporting primary data on LTBI management. Study selection, data management and data synthesis were protocol-driven (PROSPERO-CRD42021208715). Primary outcomes were the proportions of LTBI, initiating and completing tuberculosis preventive treatment (TPT). Reported factors influencing the LTBI care cascade were qualitatively synthesised. RESULTS: From 3694 unique records retrieved, 58 studies from 23 countries were included. Most identified contacts were screened (median 99%, interquartile range [IQR] 82%-100%; 46 studies). Random-effects meta-analysis yielded pooled proportions for: LTBI 41% (95% confidence interval [CI] 33%-49%; 21,566 tested contacts); TPT initiation 91% (95% CI 79%-97%; 129,573 eligible contacts, 34 studies); TPT completion 65% (95% CI 54%-74%; 108,679 TPT-initiated contacts, 28 studies). Heterogeneity was significant (I2 ≥ 95%-100%) and could not be explained in subgroup analyses. Median proportions (IQR) were: LTBI 44% (28%-59%); TPT initiation 86% (60%-100%); TPT completion 68% (44%-82%). Nine broad themes related to diagnostic testing, health system structure and functions, risk perception, documentation and adherence were considered likely to influence the LTBI care cascade. CONCLUSION: The proportions of household contacts screened, detected with LTBI and initiated on TPT, though variable was high, but the proportions completing TPT were lower indicating current strategies used for LTBI management in high TB burden countries are not sufficient.

Isoniazid Adherence Reduces Mortality and Incident Tuberculosis at 96 Weeks Among Adults Initiating Antiretroviral Therapy With Advanced Human Immunodeficiency Virus in Multiple High-Burden Settings.

Background: People with human immunodeficiency virus (HIV) and advanced immunosuppression initiating antiretroviral therapy (ART) remain vulnerable to tuberculosis (TB) and early mortality. To improve early survival, isoniazid preventive therapy (IPT) or empiric TB treatment have been evaluated; however, their benefit on longer-term outcomes warrants investigation. Methods: We present a 96-week preplanned secondary analysis among 850 ART-naive outpatients (≥13 years) enrolled in a multicountry, randomized trial of efavirenz-containing ART plus either 6-month IPT (n = 426) or empiric 4-drug TB treatment (n = 424). Inclusion criteria were CD4 count <50 cells/mm3 and no confirmed or probable TB. Death and incident TB were compared by strategy arm using the Kaplan-Meier method. The impact of self-reported adherence (calculated as the proportion of 100% adherence) was assessed using Cox-proportional hazards models. Results: By 96 weeks, 85 deaths and 63 TB events occurred. Kaplan-Meier estimated mortality (10.1% vs 10.5%; P = .86) and time-to-death (P = .77) did not differ by arm. Empiric had higher TB risk (6.1% vs 2.7%; risk difference, -3.4% [95% confidence interval, -6.2% to -0.6%]; P = .02) and shorter time to TB (P = .02) than IPT. Tuberculosis medication adherence lowered the hazards of death by ≥23% (P < .0001) in empiric and ≥20% (P < .035) in IPT and incident TB by ≥17% (P ≤ .0324) only in IPT. Conclusions: Empiric TB treatment offered no longer-term advantage over IPT in our population with advanced immunosuppression initiating ART. High IPT adherence significantly lowered death and TB incidence through 96 weeks, emphasizing the benefit of ART plus IPT initiation and completion, in persons with advanced HIV living in high TB-burden, resource-limited settings.

Barriers and facilitators for isoniazid preventive therapy (IPT) administration in children under 5 years of age in the Dominican Republic.

INTRODUCTION: Throughout the world tuberculosis (TB) is the second leading cause of death due to an infectious agent. The World Health Organization promotes Isoniazid Preventive Therapy (IPT) in children under 5 years who are contacts of persons diagnosed with smear-positive pulmonary TB (SPPTB). In 2019, 33% of children identified as contacts received IPT globally, while in the Americas 11 countries reached coverages ≥ 75%, only 35% did so in the Dominican Republic (DR). The aim of this study was to identify barriers and facilitators for IPT administration in children under 5 in the Area IV Directorate of Health of the DR's National District. METHODS: Descriptive study, using mixed methods and sequential explanatory approach. We characterized children under 5 years who were contacts of a person with SPPTB. Later, semi-structured interviews and content analysis allowed identification of barriers and facilitators for IPT administration in children who were contacts of a person diagnosed with SPPTB, as perceived by relatives and health system personnel. RESULTS: A total of 238 children were identified as contacts of 174 persons with SPPTB: 36% of these received IPT while no data on IPT administration was found for 11% of them. The proportion of children who had a tuberculin skin test (TST) done was < 20%. However, those who had the test done had a greater opportunity to receive IPT (OR: 8.12, CI 95%: 1.60-41.35). Barriers identified include socioeconomic conditions of children and families, stigma, lack of information in clinical and follow-up records, lack of coordination between public and private providers and lack of coherence within national regulations. Facilitators include home based care of persons with TB and their contacts, transfer of treatment to a health centre near household, isoniazid availability, provision of information by health-workers and economic support for food and transportation. CONCLUSIONS: Incomplete data, lack of use of TST to rule out active TB, socioeconomic and cultural conditions, were barriers for IPT administration. Implementation of a person centred approach to care was found to be the main facilitator for IPT uptake. Administration of IPT depends predominantly on modifiable health system factors. This allows rapid identification of strategies to improve IPT administration.

Adherence to Isoniazid Preventive Therapy among children living with tuberculosis patients in Delhi, India: An exploratory prospective study.

INH Preventive Therapy (IPT) substantially reduces the risk of incidence of TB disease in pediatric household contacts of TB patients. The National TB Elimination Program (NTEP) of India prescribes a daily regimen of Isoniazid to all under-6 pediatric contacts for 6 months duration. We conducted, this exploratory prospective study (June to Nov' 2020) to assess adherence to IPT and reasons for nonadherence among child contacts of microbiologically confirmed, drug sensitive, non-PLHIV Tuberculosis patients in Delhi, India. The study outcomes included the initiation, adherence and completion of IPT. The caregivers of the child TB contacts were interviewed face to face by the field investigator. The data were entered on EpiData 3.1 and analysed with IBM SPSS 25. The INH adherence was assessed in a total of 86 household child TB contacts. IPT had been initiated in 62 (72.1%) child TB contacts of which 61 (98.4%) received INH within 1 month of starting of ATT-DOTS therapy in the index TB patient of the household. Furthermore, the failure to initiate IPT was reported by 24 (27.9%) child TB contacts. Within the cohort of child TB contacts who were not initiated with IPT, the ATT-DOTS duration in the index-TB patient was ≥5 months in 18 (75%) cases, 1-2 months in 3 (12.5%) cases, and <1 month in also 3 (12.5%) cases. Reasons for non-initiation (n = 24) were reported as refusal by the family in 12 (50%) cases mostly due to concern over side-effects of the drug, while non-provision of the drug by the DOTS provider was also observed in 12 (50%) cases. The mean (SD) INH adherence in the INH initiated cohort was 5.6 (2.0) (n = 62). Reasons for INH non-adherence were attributed to forgetfulness (n = 23, 37.1%), carelessness (n = 24, 38.7%), and intermittent stopping of the medication (n = 17, 27.4%) on the child falling sick, perceived drug side effects, and running out of drug stocks. INH non-adherence defined as at-least two missed INH doses in the previous 7 days was observed in 47 (54.7%) participants (n = 86). On bivariate analysis, none of the household sociodemographic characteristics showed any statistically significant association with the rate of INH non-adherence in the child TB contacts. The findings of the present study indicate the need to periodically assess adherence and persistence to IPT in the child TB contacts as high intermittent missed dosing rates can undermine the effectiveness of IPT in preventing incident disease.

Effect of mobile-phone messaging on patient and health-worker knowledge and adherence to the isoniazid preventive therapy guideline in HIV clinics in Southeast, Nigeria.

BACKGROUND: HIV-infected persons are at increased risk of developing tuberculosis and Isoniazid preventive therapy has been shown to reduce the occurrence of tuberculosis among this group of persons. M-health technology has been reported to increase both knowledge and implementation of various health services including Isoniazid preventive therapy implementation. This study aimed to determine the effect of m-health on health worker knowledge and adherence to isoniazid preventive therapy (IPT) guidelines and on patient knowledge and adherence to isoniazid treatment. METHODS: This was a quasi-experimental study that was carried out in six health facilities in Ebonyi State, southeast Nigeria. Three health facilities were assigned to each arm (intervention and control arms) and all eligible health workers (total population of 45 and 41 in intervention and control arms respectively) were recruited. Data were also collected from 200 patients (100 per arm). The intervention consisted of mobile phone messages and reminders for health workers on the IPT guideline. Chi-square test was carried out at p < 0.05 and 95% confidence interval. RESULTS: At baseline, 54.5% and 63.4% of health workers in intervention and control arms respectively had good knowledge which improved significantly to 90.2% in the intervention arm after the intervention (χ2 = 14.22, p < 0.0001). At baseline, 61.4% and 90.2% of health workers had good adherence to the guideline in intervention and control arms respectively which also improved in the intervention arm by 28.8% after intervention although not significant(χ2 = 0.37, p = 0.54). More than 50% of the patients in both study arms had poor knowledge, with the intervention arm having a significantly higher proportion of respondents (68.0%) with poor knowledge at baseline (χ2 = 4.71, p = 0.03). The proportion of patients with good knowledge however increased significantly (88.8%) in the intervention arm after intervention (χ2 = 25.65, p < 0.001). Patients had good adherence to IPT in intervention and control arms before (100% and 84.2% respectively) and after (96.6% and 100% respectively) the study. There was no significant difference in adherence among patients in both arms. CONCLUSIONS: Health worker knowledge and practice of guidelines as well as patient knowledge improved in the intervention arm in this study. These findings suggest the consideration for the inclusion of mobile phone reminders in the guideline for tuberculosis prevention among HIV patients.

Low level of tuberculosis preventive therapy incompletion among people living with Human Immunodeficiency Virus in eastern Uganda: A retrospective data review.

INTRODUCTION: In most developing countries, tuberculosis (TB) is the leading cause of mortality among people living with the Human Immunodeficiency Virus (PLHIV). Uganda implements TB preventive therapy (TPT) using Isoniazid but data are limited about TPT incompletion. We, therefore, assessed the magnitude of TPT incompletion and the associated factors among PLHIV in a large rural referral health facility in rural eastern Uganda. METHODS AND MATERIALS: We conducted a retrospective data review for PLHIV initiated on TPT between October 2018 and September 2019. The outcome variable was TPT incompletion defined as the failure to finish 6 consecutive months of Isoniazid or failure to finish 9 months of Isoniazid without stopping for more than 2 months at a time. We descriptively summarized numerical data using frequencies and percentages and compared differences in the outcome with independent variables using the Chi-square or fisher's exact, and the Student's t-tests. We used a generalized linear model to assess factors independently associated with TPT incompletion, reported using adjusted odds ratio (aOR) and 95% confidence interval (CI). RESULTS: We enrolled 959 participants with a mean age of 41.1 ± 13.8 years, 561 (58.5%) were females, 663 (69.1%) married, 538 (56.1) travelled 5-10 km from their place of residence to the ART clinic, 293 (30.6%) had disclosed HIV status, 362 (37.7%) had been on ART for 5-9 years, and 923 (96.2%) were on first-line ART regimen. We found 26 (2.7%) participants had incomplete TPT. Non-adherence to ART clinic visits (aOR, 2.81; 95% CI, 1.09-7.73), history of switch in ART regimen (aOR, 9.33; 95% CI, 1.19-52.39), patient representation (aOR, 4.70; 95% CI, 1.35-13.99), and one unit increase in ongoing counselling session (aOR, 0.67; 95% CI, 0.46-0.91) were associated with TPT incompletion. CONCLUSION: We found low rates of TPT incompletion among PLHIV in rural eastern Uganda. Non-adherence to ART clinic visits, patient representation, and history of switch in ART regimen is associated with a higher likelihood of TPT incompletion while ongoing counselling is associated with a reduction in TPT incompletion. The health system should address non-adherence to ART clinic visits and patient representation, through ongoing psychosocial support.

Low prevalence of isoniazid preventive therapy uptake among HIV-infected patients attending tertiary health facility in Lagos, Southwest Nigeria.

INTRODUCTION: the burden of HIV and tuberculosis co-infection is a global public health challenge. Despite the benefit of isoniazid preventive therapy (IPT) in reducing the rate of co-infection, the uptake is generally limited in developing countries. This study aimed to determine the prevalence of IPT use and the factors affecting the uptake among HIV-infected patients attending our Teaching Hospital. METHODS: this cross-sectional survey involved 300 HIV-infected individuals attending the AIDS prevention initiatives in Nigeria clinic of the Lagos University Teaching Hospital. A self-designed and well-structured questionnaire was used to document the demographic data, patients' exposure to tuberculosis, and IPT uptake. Clinical data of eligible patients were also extracted from their case notes. The main outcome measure was the prevalence of IPT use and non-use. RESULTS: out of the respondents evaluated, (72.7%, n = 218) were females. Tuberculosis was the predominant comorbidity (15.7%, n = 47) and majority (53.0%, n = 159) had a CD4 count of < 500 cells/ml. Overall prevalence of IPT uptake was very low (7.1%, n = 18) among HIV-infected patients. Major factors affecting uptake were lack of awareness of benefit (44.4%, n = 8) and lack of fear of contracting tuberculosis (22.2%, n = 4). However, lack of awareness of IPT benefit was the only independent factor associated with poor IPT uptake (adjusted odds 1168.75, 95% confidence interval: 85.05-16060.33; p = 0.001). CONCLUSION: isoniazid preventive therapy uptake was found to be very low in this study. Increased awareness and policy implementation of IPT by the healthcare provider is necessary.