Tuberculosis Preventive Therapy Research Articles

Sex differences in tuberculosis infection and disease among people with HIV.

Worldwide, adult men experience an excess burden of tuberculosis (TB) disease compared to women, but few studies have examined sex differences in TB among people with HIV. In this study, we aimed to investigate sex differences in TB infection and disease among people with HIV in Rio de Janeiro, Brazil. Analysis of data from a randomized controlled trial and retrospective cohort study. We analyzed data from two studies conducted between 2005 and 2017. The THRio Study (2005-2012) evaluated increasing tuberculin skin testing (TST) and TB preventive therapy (TPT) and UnivART (2010-2017) was a virtual cohort study of people with HIV and TB with data from four national electronic registries. Among 4,606 people with HIV in THRio, 2,992 (65.0%) had a TST placed and read, of whom 312/1,865 (17%) males and 203/1,127 (18%) females (p = 0.37) had prevalent TB infection. TB disease incidence was higher among males compared to females overall (IRR 1.33, 95% CI 1.04-1.69), among males compared to females who did not receive TPT (IRR 1.30, 95% CI 1.01-1.67), and among males compared to females on ART (IRR 1.64, 95% CI 1.17-2.29). Among 54,957 people with HIV in UnivART, TB disease incidence rates were higher among males than females overall (IRR 1.28, 95% CI 1.18-1.39), among males compared to females on ART (IRR 1.58, 95% CI 1.40-1.77), and among males compared to females not on ART (IRR 1.11, 95% CI 0.99-1.25). In this medium TB and HIV burden setting, TB disease incidence was higher among males than females with HIV, despite similar prevalence of TB infection.

HIV replication and tuberculosis risk among people living with HIV in Europe: A multicohort analysis, 1983-2015.

HIV replication leads to a change in lymphocyte phenotypes that impairs immune protection against opportunistic infections. We examined current HIV replication as an independent risk factor for tuberculosis (TB). We included people living with HIV from 25 European cohorts 1983-2015. Individuals <16 years or with previous TB were excluded. Person-time was calculated from enrolment (baseline) to the date of TB diagnosis or last follow-up information. We used adjusted Poisson regression and general additive regression models. We included 272,548 people with a median follow-up of 5.9 years (interquartile range [IQR] 2.3-10.9). At baseline, the median CD4 cell count was 355 cells/μL (IQR 193-540) and the median HIV-RNA level 22,000 copies/mL (IQR 1,300-103,000). During 1,923,441 person-years of follow-up, 5,956 (2.2%) people developed TB. Overall, TB incidence was 3.1 per 1,000 person-years (95% confidence interval [CI] 3.02-3.18) and was four times higher in patients with HIV-RNA levels of 10,000 compared with levels <400 copies/mL in any CD4 stratum. CD4 and HIV-RNA time-updated analyses showed that the association between HIV-RNA and TB incidence was independent of CD4. The TB incidence rate ratio for people born in TB-endemic countries compared with those born in Europe was 1.8 (95% CI 1.5-2.2). Our results indicate that ongoing HIV replication (suboptimal HIV control) is an important risk factor for TB, independent of CD4 count. Those at highest risk of TB are people from TB-endemic countries. Close monitoring and TB preventive therapy for people with suboptimal HIV control is important.

Management implications of latent TB among under-five children at risk: Insights from a community study in Mumbai, India.

Latent tuberculosis infection (LTBI) management is crucial to WHO's End TB Strategy. Indian guidelines recommend treating under-five children with household TB contacts after ruling out active TB, regardless of TBI testing. However, the precise LTBI burden among children in high TB burden settings like India is unknown. A community-based study in Mumbai's urban slums screened and managed under-five children at LTBI risk to understand its epidemiology and inform TB control interventions. Total 369 eligible under-five children were enrolled for the study. LTBI screening was done using Tuberculin skin test and Interferon gamma release assay. Active TB was ruled out before initiation of TB preventive therapy among LTBI positives. Statistical tests like chi-square, logistic regression analysis and Hosmer-Lemeshow test were used. Overall, LTBI prevalence among under-five children was 12.4% by IGRA and 21.4% by TST. Undernourished children had significantly lower LTBI positivity by IGRA (p = 0.027), while those with household contacts, longer contact duration and drug-resistant tuberculosis (DR-TB) exhibited proportionally greater IGRA positivity (p = <0.001). The study found a lower LTBI prevalence among under-five children compared to adults, with key risk factors being HHC, DR-TB contact, and prolonged exposure. These findings suggest the need to revise or revisit the TPT framework for this age group in India, particularly by implementing a test-and-treat approach.

Analysis of Tuberculosis Control (Case Study in The City of Mojokerto) Year 2024

This study aims to analyze the tuberculosis (TB) situation in Mojokerto City, focusing on the increase in cases among children and identifying effective countermeasures. TB, a preventable and curable infectious disease caused by Mycobacterium tuberculosis, is particularly problematic in developing countries like Indonesia due to high incidence and mortality rates, necessitating a comprehensive control strategy. Employing qualitative methods, this research delves into the practices, perceptions, and social dynamics affecting TB control efforts in Mojokerto, illuminated by the latest data showing a significant increase in pediatric TB cases and the public health situation. Findings reveal a TB incidence rate of 385 per 100,000 inhabitants, a case detection rate of 75%, and a notably high pediatric TB case proportion of 32%. The effectiveness of case tracking by health centers varies, with an average of only 54% receiving Tuberculosis Preventive Therapy (TPT). Major obstacles include limited access to radiology services, social stigma, and the need for adequate health facilities. Innovations such as the "Mbak Desi Fights TB" program and enhanced cross-sector cooperation are deemed crucial to strengthen control strategies. The study concludes that a multifaceted strategy is essential for combating TB in Mojokerto, which should include enhanced case detection, health system strengthening, and community integration in control efforts. Increased collaboration across sectors and advancements in research and development are expected to accelerate TB elimination. This research offers efficient recommendations to improve TB control strategies, based on an in-depth analysis of the current conditions and social dynamics in Mojokerto.

Critical assessment of infants born to mothers with drug resistant tuberculosis

There have been no detailed descriptions of infants born to mothers treated for drug resistant TB in pregnancy. Critical case history assessment is important to identify risks and guide clinical practice. In a cohort of pregnant women with multidrug or rifampicin resistant (MDR/RR)-TB enrolled between 1 January 2013 and 31 December 2022, we followed mother-infant pairs until the infant was 12 months old. We performed critical case history assessments to explore potential mechanisms of Mycobacterium tuberculosis transmission to the infant, and to describe the clinical presentation and disease trajectories observed in infants diagnosed with TB. Among 101 mother-infant pairs, 23 (23%) included infants diagnosed with TB disease; 16 were clinically diagnosed and seven had microbiological confirmation (five MDR/RR-TB, two drug-susceptible TB). A positive maternal sputum culture at the time of delivery was significantly associated with infant TB risk (p=0.023). Of the 12 infants diagnosed with TB in the first three months of life, seven (58%) of the mothers were culture positive at delivery; of whom four reported poor TB treatment adherence. However, health system failures, including failing to diagnose and treat maternal MDR/RR-TB, inadequate screening of newborns at birth, not providing appropriate TB preventive therapy (TPT), and M.tuberculosis transmission from non-maternal sources also contributed to TB development in infants. Infants born to mothers with MDR/RR-TB are at greatest risk if maternal adherence to MDR/RR-TB treatment or antiretroviral therapy (ART) is sub-optimal. In a high TB incidence setting, infants are also at risk of non-maternal household and community transmission. Ensuring maternal TB diagnosis and appropriate treatment, together with adequate TB screening and prevention in all babies born to mothers or households with TB will minimise the risk of infant TB disease development. South African Medical Research Council.

Three months of weekly rifapentine plus isoniazid for TB prevention among people with HIV

&lt;sec&gt;&lt;title&gt;BACKGROUND&lt;/title&gt;Evidence on implementation of three months of weekly isoniazid (H, INH) and rifapentine (P, RPT) (3HP) as a TB preventive therapy (TPT) for at-risk groups in Indian programmatic conditions is limited.&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;METHODS&lt;/title&gt;A prospective demonstration study assessing scale-up, safety, and effectiveness of 3HP TPT among people living with HIV (PLHIV) in Indian programmatic settings was conducted.&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;RESULTS&lt;/title&gt;Of 656 screened PLHIV, 502 (77%) received 3HP. Of these, 20 (4%) discontinued TPT due to toxicity,17 (3.8%) lost to follow-up, one (0.2%) had breakthrough rifampicin-sensitive TB, and 464 (92%) completed 3 HP TPT. Of 288 (57%) overall adverse events (AEs), 46 (9%) had Grade 2 or above AEs. The median time to AE was 14 days (IQR 7–42). Serious adverse events (SAEs) were reported in 9 (2%) participants; of these, 7 (78%) were not related to 3HP. No TB episodes occurred during the 1-year follow-up period.&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;CONCLUSION&lt;/title&gt;3HP TPT completion rate of 92%, with few adverse events leading to 3HP discontinuation, providing evidence of the scalability and safety of 3HP TPT among PLHIV in Indian health program settings.&lt;/sec&gt;

3HP preventive treatment among children and adolescents with HIV and child household contacts of TB patients

&lt;sec&gt;&lt;title&gt;INTRODUCTION&lt;/title&gt;India’s National TB Elimination Programme plans to roll out short-course TB preventive therapy (TPT) using 3 months of rifapentine and isoniazid (3HP). Understanding the feasibility and safety of children in programmatic settings is critical for widespread implementation. We present the findings of a targeted scale-up of 3HP among children and adolescents living with HIV (CALHIV) and child household contacts (&gt;2 to &lt;6 years) of pulmonary TB patients (CHHC).&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;METHODS&lt;/title&gt;Between December 2021 and July 2023, eligible CALHIV and CHHC participants were given weekly dosages of 3HP for 3 months at antiretroviral therapy (ART) and TB clinics, respectively, of a public hospital in Pune, India.&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;RESULTS&lt;/title&gt;Of 97 children screened, 91 initiated 3HP (32 CALHIV and 59 CHHC). The median age of CALHIV was 14 years; 66% were male and on dolutegravir-based ART. The median age of CHHC was 4 years; 47% were males. Thirty-one (97%) CALHIV and 56 (95%) CHHC completed 3HP without dolutegravir dose adjustment. None of the child participants discontinued 3HP due to adverse events. No child participant developed TB during 1 year of follow-up post-3HP.&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;CONCLUSION&lt;/title&gt;Our study provides evidence of the uptake and feasibility of the planned nationwide rollout of 3HP.&lt;/sec&gt;

Evaluating the cost-effectiveness of Cy-Tb for LTBI in India: a comprehensive economic modelling analysis.

Latent tuberculosis infection (LTBI) remains a significant challenge, as there is no gold standard diagnostic test. Current methods used for identifying LTBI are the interferon-γ release assay (IGRA), which is based on a blood test, and the tuberculin skin test (TST), which has low sensitivity. Both these tests are inadequate, primarily because they have limitations with the low bacterial burden characteristic of LTBI. This highlights the need for the development and adoption of more specific and accurate diagnostic tests to effectively identify LTBI. Herein we estimate the cost-effectiveness of the Cy-Tb test as compared with the TST for LTBI diagnosis. An economic modelling study was conducted from a health system perspective using decision tree analysis, which is most widely used for cost-effectiveness analysis using transition probabilities. Our goal was to estimate the incremental cost and number of TB cases prevented from LTBI using the Cy-Tb diagnostic test along with TB preventive therapy (TPT). Secondary data such as demographic characteristics, treatment outcome, diagnostic test results and cost data for the TST and Cy-Tb tests were collected from the published literature. The incremental cost-effectiveness ratio was calculated for the Cy-Tb test as compared with the TST. The uncertainty in the model was evaluated using one-way sensitivity analysis and probability sensitivity analysis. The study findings indicate that for diagnosing an additional LTBI case with the Cy-Tb test and to prevent a TB case by providing TPT prophylaxis, an additional cost of 18658 Indian rupees (US${\$}$223.5) is required. The probabilistic sensitivity analysis indicated that using the Cy-Tb test for diagnosing LTBI was cost-effective as compared with TST testing. If the cost of the Cy-Tb test is reduced, it becomes a cost-saving strategy. The Cy-Tb test for diagnosing LTBI is cost-effective at the current price, and price negotiations could further change it into a cost-saving strategy. This finding emphasizes the need for healthcare providers and policymakers to consider implementing the Cy-Tb test to maximize economic benefits. Bulk procurements can also be considered to further reduce costs and increase savings.

HIV-associated tuberculosis in infants, children, and adolescents younger than 15 years: an update on the epidemiology, diagnosis, prevention, and treatment.

HIV-associated tuberculosis (TB) remains a major driver of morbidity and mortality in children and adolescents younger than 15 years (CLWH). The purpose of this review is to highlight recent findings in the areas of prevention, diagnosis, and treatment of HIV-associated TB in CLWH and to highlight knowledge and implementation gaps. We found that despite access to antiretroviral therapy (ART), high rates of HIV-associated TB are still reported, and with an unacceptably high mortality. There are no advances in screening for TB, but shorter courses of rifapentine-based TB preventive therapy are becoming available. The use of algorithms in TB diagnosis can potentially simplify the therapeutic decision making. There are more data supporting the use of dolutegravir (DTG) with rifampicin and a need to study unadjusted DTG especially in the youngest children. Short course therapy for nonsevere pulmonary TB is currently implemented and programmatic outcome should be studied in CLWH. Low uptake of ART and poor suppression remains an important driver of HIV-associated TB. Although screening and diagnosis remains challenging, there are several advances in the prevention and treatment of HIV-associated TB. Effective implementation of these strategies is needed to advance the outcomes of CLWH.

Comparison of QuantiFERON Gold In-Tube Versus Tuberculin Skin Tests on the Initiation of Tuberculosis Preventive Therapy Among Patients Newly Diagnosed With HIV in the North West Province of South Africa (the Teko Study): A Cluster Randomized Trial.

Tuberculosis (TB) preventive therapy (TPT) reduces the risk of TB disease in people with human immunodeficiency virus (HIV), yet uptake has been suboptimal in many countries. We assessed whether QuantiFERON Gold In-Tube (QGIT) during routine HIV care increased TB infection (TBI) testing and TPT prescriptions. This parallel-arm, 1:1 cluster-randomized controlled trial compared the standard-of-care tuberculin skin test to QGIT in South Africa. We enrolled consenting, TPT-eligible adults diagnosed with HIV ≤30 days prior and used intention-to-treat analyses for the outcomes: proportion of patients with documented TBI results, proportion with documented TPT, and time from enrollment to outcomes. We enrolled 2232 patients across 14 clinics from November 2014 to May 2017 (58% in intervention clinics). At 24 months of follow-up, more participants in intervention clinics had TBI results (69% vs 2%, P < .001) and TPT prescriptions (45% vs 30%, P = .13) than control clinics. Controlling for baseline covariates, intervention clinics had 60% (95% confidence interval, 51-68; P < .001) more participants with TBI results and 12% (95% confidence interval, -6 to 31; P = .18) more with TPT prescriptions. Among participants with results, those in intervention clinics received results and TPT faster (intervention: median of 6 and 29 days after enrollment vs control: 21 and 54 days, respectively). In this setting, QGIT in routine HIV care resulted in more patients with TBI results. Clinicians also initiated more people with HIV on TPT in QGIT intervention clinics, and did so more quickly, than the control arm. NCT02119130.

Paving a Way for “TB Mukt Bharat”: A Snapshot of India's TB Elimination Program

AbstractTuberculosis (TB) remains a significant global health challenge, particularly in countries like India, where it is a leading cause of mortality. This article provides an overview of India's efforts to combat TB through its national TB programs, tracing their evolution from the National TB Program in 1962 to the current National TB Elimination Program (NTEP) launched in 2020. The NTEP aims to eliminate TB by ensuring universal access to high-quality diagnosis and treatment services. The program emphasizes prevention, detection, treatment, and capacity building, aligning with global initiatives like the World Health Organization's End TB Strategy. Key components of the NTEP include free diagnostic services, treatment regimens for drug-sensitive and drug-resistant TB, and TB preventive therapy. The program also includes robust patient support systems, such as incentive schemes and transport support, to improve treatment outcomes. Through these comprehensive strategies, India seeks to achieve its goal of a TB-free nation by 2025, aligning with global Sustainable Development Goals.

Strategies for isoniazid preventive therapy in HIV-positive patients who consume alcohol.

<sec><title>BACKGROUND</title>WHO guidance to defer isoniazid preventive therapy (IPT) among those with regular alcohol use because of hepatotoxicity concerns may exclude many people living with HIV (PLWH) at high TB risk in these settings.</sec><sec><title>OBJECTIVE</title>To evaluate hepatotoxicity during TB preventive therapy (TPT) in PLWH who report alcohol use in Uganda over 10 years.</sec><sec><title>METHODS</title>We developed a Markov model of latent TB infection, isoniazid preventive therapy (IPT - a type of TPT), and TB disease using data from the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) study. We modeled several treatment scenarios, including no IPT, IPT with liver enzyme monitoring (AST/ALT) during treatment, and IPT with pre-screening using the tuberculin skin test (TST).</sec><sec><title>RESULTS</title>The no IPT scenario had 230 TB deaths/100,000 population over 10 years, which is more than that seen in any IPT scenario. IPT, even with no monitoring, was preferred over no IPT when population TB disease incidence was >50 in 100,000.</sec><sec><title>CONCLUSIONS</title>For PLWH who report alcohol use in high TB burden settings, IPT should be offered, ideally with regular AST/ALT monitoring. However, even if regular monitoring is not possible, IPT is still preferable to no IPT in almost every modeled scenario.</sec>.

Challenges of Screening and Investigations of Contacts of Patients with Tuberculosis in Oyo and Osun States, Nigeria.

Tuberculosis (TB) remains a significant public health challenge in Nigeria, with high rates of transmission and low case detection rates. This paper presents the challenges of screening and investigation of contacts of patients with TB in Oyo and Osun State, Nigeria. This descriptive-qualitative study was conducted in eight Local Government Areas with high TB burdens. Twenty-four focus group discussions and 30 key informant interviews were conducted among TB patients, household TB contacts, and government TB staff, among others. Respondents ages ranged from 17-85 years with a mean of 42.08 ± 14.9 years, and (4.0%) had a postgraduate degree. This study identified that the majority of TB contacts who tested negative for TB were unwilling to be placed on TB preventive therapy because of the belief that only a sick person should take drugs. Also, hostility from the TB contacts to the contact tracers during the house-to-house screening of presumptive TB cases due to community stigma associated with TB was another existing gap reported in TB contact investigations. The findings emphasise the importance of tailored approaches in TB prevention and control, addressing challenges in testing and contact investigations; this necessitates investments in community engagement strategies to enhance the cooperation of TB contacts.

Tuberculosis preventive treatment in eight SEAR countries – Current practices, implementation challenges and operations research priorities

ObjectivesCountries in the South East Asian region face similar challenges in control of infectious diseases. There is limited access to experiences and learnings of neighboring countries. The Indian Council - of Medical Research (ICMR) has established a Regional Enabler for the South-East Asia Research Collaboration for Health (RESEARCH) Platform for South East Asian Region (SEAR) countries to address the above issues. This paper discusses about current practices, implementation challenges and operations research priorities of Tuberculosis Preventive therapy (TPT) in eight SEAR countries. MethodsA three day workshop on “Capacity Building for TB Research under Programmatic Settings”. was conducted under the aegis of this RESEARCH platform jointly ICMR and the Union which was participated by eight SEAR countries. Data were collected from a semi-structured questionnaire prior to the workshop and open discussions during the workshop. ResultsThe various challenges faced for TPT implementation were broadly categorized as poor demand and low level of acceptance by the beneficiary, low level of acceptance to provide TPT among the providers, challenges in ruling out active TB, issues with supply and supply chain management of diagnostic tests and drugs. Many operations research priorities like person centric TPT driven models, capacity building for improving cascade of care for latent TB infection, health system strengthening and effective risk communication were identified. ConclusionFull implementation of the TPT guidelines requires focused attention and coordinated action from all stakeholders of the country to attain the full benefit of TB preventive therapy and the ultimate TB elimination goal.

Completion of tuberculosis preventive therapy and associated factors among clients on antiretroviral therapy at Debre Berhan town health facilities, North Shoa Zone, Ethiopia

BackgroundTuberculosis preventive therapy is vital in caring for HIV-positive individuals, as it prevents the progression from latent tuberculosis infection to tuberculosis disease. The aim of the study is to assess the completion of tuberculosis preventive therapy and associated factors among clients receiving antiretroviral therapy in Debre Berhan town, Ethiopia, in 2022.MethodInstitutional based cross sectional study was conducted. Random sampling methods were used to select both study participants and health facilities. Both bivariate and multivariate logistic regression analyses were performed. P-values less than 0.05 were statistically significant.ResultThe study found that, 83% of participants were completed tuberculosis preventive therapy. Completed tuberculosis preventive therapy was associated with no adverse drug events, taking first-line ART, and good ART adherence.ConclusionAccording to the Ethiopian ART guidelines, the study found a low completion rate of tuberculosis preventive therapy among HIV-positive clients on antiretroviral therapy. Factors like no adverse drug events, first-line antiretroviral regimen, and good adherence were significantly associated with completing tuberculosis preventive therapy.

Integrated management of cryptococcal meningitis and concurrent opportunistic infections to improve outcomes in advanced HIV disease: a randomised strategy trial

Background Mortality associated with HIV-associated cryptococcal meningitis remains high even in the context of clinical trials (24–45% at 10 weeks); mortality at 12-months is up to 78% in resource limited settings. Co-prevalent tuberculosis (TB) is common and preventable, and likely contributes to poor patient outcomes. Innovative strategies to increase TB preventative therapy (TPT) provision and uptake within this high-risk group are needed. Protocol The IMPROVE trial (Integrated management of cryptococcal meningitis and concurrent opportunistic infections to improve outcomes in advanced HIV disease) is a nested open label, two arm, randomised controlled strategy trial to evaluate the safety (adverse events) and feasibility (adherence and tolerability) of two ultra-short course TPT strategies, in the context of recent diagnosis and treatment for cryptococcal meningitis. We will enrol 205 adults with HIV-associated cryptococcal meningitis from three hospitals in Uganda. Participants will be randomised to either inpatient initiation (early) or outpatient initiation (standard, week 6) of 1HP (one month of isoniazid and rifapentine). Participant follow-up is to include TB screening, 1HP pill counts and tolerability reviews on alternate weeks until week-18. The trial primary endpoint is TB-disease free 1HP treatment completion at 18-weeks, secondary endpoints: 1HP treatment completion, 1HP discontinuation, grade ≥3 adverse events and serious adverse events, drug-induced liver injury, incident active TB, 18-week survival; rifapentine, fluconazole and dolutegravir concentrations will be measured with intensive sampling in a pharmacokinetic sub-study of 15 eligible participants. Discussion The IMPROVE trial will provide preliminary safety and feasibility data to inform 1HP TPT strategies for adults with advanced HIV disease and cryptococcal meningitis. The potential impact of demonstrating that inpatient initiation of 1HP TPT is safe and feasible amongst this high-risk subpopulation with advanced HIV disease, would be to expand the range of clinical encounters in which clinicians can feasibly provide 1HP, and therefore increase the reach of TPT as a preventative intervention. ISRCTN registration ISRCTN18437550 (05/11/2021)

Factors Associated With the Discontinuation of Two Short-Course Tuberculosis Preventive Therapies in Programmatic Settings in the United States.

The objective of this study was to investigate timing and risk factors for discontinuation of short-course tuberculosis preventive therapy (TPT) comparing directly observed 3-month isoniazid/rifapentine (3HP) vs self-administered 4-month rifampin (4R). This was a subanalysis of a 6-month health department cohort (2016-2017) of 993 latent tuberculosis infection (LTBI) patients initiating 3HP (20%) or 4R (80%). Time at risk of TPT discontinuation was compared across regimens. Risk factors were assessed using mixed-effects Cox models. Short-course TPT discontinuation was higher with 4R (31% vs 14%; P < .0001), though discontinuation timing was similar. Latino ethnicity (hazard ratio [HR], 1.80; 95% CI, 1.20-2.90) and adverse events (HR, 4.30; 95% CI, 2.60-7.30) increased 3HP discontinuation risk. Social-behavioral factors such as substance misuse (HR, 12.00; 95% CI, 2.20-69.00) and congregate living (HR, 21.00; 95% CI, 1.20-360.00) increased 4R discontinuation risk. TPT discontinuation differed by regimen, with distinct risk factors. Addressing social determinants of health within TPT programs is critical to enhance completion rates and reduce TB disease risk in marginalized populations.

Clinical Predictors of 3-Months Isoniazid Rifapentine (3HP) - Related Adverse Drug Reactions (ADR) During Tuberculosis Preventive Therapy. (PAnDoRA-3HP study): An Observational Study Protocol.

Tuberculosis (TB) is the leading infectious cause of death globally. Despite WHO recommendations for Tuberculosis Preventive Therapy (TPT), challenges persist, including incompletion of treatment and adverse drug reactions (ADRs). There is limited data on the 3-month isoniazid and rifapentine (3HP) pharmacokinetics, pharmacogenomics and their relation with ADRs. Our study aims to describe the pharmacokinetic and pharmacogenomics of 3HP used for TPT, the ADRs and their association with completion rates, and TPT outcomes, providing vital insights for TB control strategies in resource-limited settings. This is an observational cohort study with a nested case-control study. We enrolled consecutive patients initiated on TPT using the 3HP regimen. These are followed up bi-weekly and then monthly during the active phase of treatment and 3 monthly for 2 years following completion of TPT. ADR evaluation includes clinical assessment and liver function tests. Cases are selected from those who experience ADRs, and controls from those who do not. Serum isoniazid and rifapentine concentrations are measured and pharmacogenomic analysis for NAT2 and CYP2E1 polymorphisms are done. Participants are followed up for 2 years to determine TPT outcomes. The safety profile of 3HP will be assessed using descriptive statistics, including proportions of patients experiencing ADRs and grade 3 or above events related to treatment. Chi-square tests and regression models will determine predictors of ADRs and their impact on treatment completion. Pharmacokinetic-pharmacodynamic modeling will establish population parameters and factors influencing rifapentine and isoniazid concentrations.

Facilitators and barriers to optimum uptake of multimonth dispensing of antiretroviral treatment in Morogoro, Tanzania: a qualitative study

ObjectivesAimed at determining facilitators and barriers to optimum uptake of multimonth dispensing (MMD) of antiretroviral treatment (ART).DesignQualitative study conducted through in-depth interviews.SettingAn explorative qualitative approach conducted at three high-volume care...

Latent tuberculosis infection care cascade among the household contacts of pulmonary tuberculosis patients – Findings from an urban feasibility study

IntroductionLatent Tuberculosis infection (LTBI) care cascade involves identification of high-risk individuals, testing, identification of LTBI, initiation of Tuberculosis Preventive therapy (TPT) and documentation of outcomes. There is a dearth of such evidence in Indian setting which needs to be further explored. Hence, this feasibility study with public private engagement was conducted with the primary objective of estimating the prevalence of LTBI among household contacts (HHCs) of pulmonary tuberculosis patients using Interferon gamma release assay (IGRA). Secondary objective was to determine the treatment outcomes among the patients of LTBI initiated on TPT. MethodsThis longitudinal community-based study was conducted in wards 47–51 at urban field practice area of our Tertiary Teaching Institute at Bhopal, Madhya Pradesh. The household contacts of pulmonary tuberculosis patients diagnosed from January–June 2022 and those who satisfied the study criteria were recruited. Those who gave consent for IGRA testing and TPT initiation were followed up for a period of 6 months to assess the treatment outcomes. Data was analyzed using R software. ResultsOf the 64 HHCs screened, 29 were the contacts of microbiologically positive and 35 were the contacts of clinically diagnosed index Tb patients including 4 under five children. Prevalence of LTBI using IGRA was 74.5%. The Contact Investigation Coverage in the urban setting was 77.1% with TPT completion of 72.4% and TPT Coverage of 55.7%. The median time for screening the HHCs since the diagnosis of index case was 14 days while screening to diagnosis was 2.5 days and that of TPT initiation from diagnosis was 22 days. ConclusionMore than half of those who were tested using IGRA were positive for LTBI. Th public private coordination helped in narrowing the time interval from diagnosis of index tb case to contact tracing and improving the TPT adherence among the HHCs. However, intensive efforts are required to narrow the screening gap of HHCs and TPT initiation. Also, reasons for loss to follow up and missed doses needs to be qualitatively explored.