Health System Costs of Treating Latent Tuberculosis Infection With Four Months of Rifampin Versus Nine Months of Isoniazid in Different Settings.

BACKGROUND: Four months of rifampin treatment for latent tuberculosis infection is safer, has superior treatment completion rates, and is as effective as 9 months of isoniazid. However, daily medication costs are higher for a 4-month rifampin regimen than a 9-month isoniazid regimen. OBJECTIVE: To compare health care use and associated costs of 4 months of rifampin and 9 months of isoniazid. DESIGN: Health system cost comparison using all health care activities recorded during 2 randomized clinical trials. (ClinicalTrials.gov: NCT00931736 and NCT00170209). SETTING: High-income countries (Australia, Canada, Saudi Arabia, and South Korea), middle-income countries (Brazil and Indonesia), and African countries (Benin, Ghana, and Guinea). PARTICIPANTS: Adults and children with clinical or epidemiologic factors associated with increased risk for developing tuberculosis that warranted treatment for latent tuberculosis infection. MEASUREMENTS: Health system costs per participant. RESULTS: A total of 6012 adults and 829 children were included. In both adults and children, greater health system use and higher costs were observed with 9 months of isoniazid than with 4 months of rifampin. In adults, the ratios of costs of 4 months of rifampin versus 9 months of isoniazid were 0.76 (95% CI, 0.70 to 0.82) in high-income countries, 0.90 (CI, 0.85 to 0.96) in middle-income countries, and 0.80 (CI, 0.78 to 0.81) in African countries. Similar findings were observed in the pediatric population. LIMITATION: Costs may have been overestimated because the trial protocol required a minimum number of follow-up visits, although fewer than recommended by many authoritative guidelines. CONCLUSION: A 4-month rifampin regimen was safer and less expensive than 9 months of isoniazid in all settings. This regimen could be adopted by tuberculosis programs in many countries as first-line therapy for latent tuberculosis infection. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Completion Rates, Adverse Effects, and Costs of a 3-Month and 9-Month Treatment Regimen for Latent Tuberculosis Infection in California Inmates, 2011-2014.

OBJECTIVES: In California, about 80% of tuberculosis disease is caused by untreated latent tuberculosis infection (LTBI), and the rate of LTBI is higher among incarcerated persons (16%) than among nonincarcerated persons (6%). We compared 2 regimens to treat LTBI in an adult prison population in California: 9 months of twice-weekly isoniazid (9H; previous standard of care) and 12 once-weekly doses of isoniazid and rifapentine (3HP; introduced in 2011). METHODS: We evaluated the rates of completion and discontinuation caused by hepatotoxicity among randomly selected patients with LTBI prescribed the 9H regimen in 2011 and among patients with LTBI prescribed the 3HP regimen who entered California prisons during September 2013-March 2014. We compared the cost per fully treated patient for the 2 regimens. RESULTS: Of 92 patients treated with the 9H regimen, the treatment completion rate was 42% and discontinuation due to hepatotoxicity was 14%. Of 122 patients who accepted the 3HP regimen, the completion rate was 90% and discontinuation due to hepatotoxicity was 2%. The cost per fully treated patient for the 9H regimen was $981 and for 3HP was $652. CONCLUSIONS: In an incarcerated population, the 3HP regimen had a higher completion rate, lower hepatotoxicity, and lower cost per fully treated patient than the 9H regimen. If coupled with a high treatment initiation rate, the high rate of LTBI treatment completion with 3HP may contribute to reducing tuberculosis morbidity in California.

Cost-effectiveness of 3 months of weekly rifapentine and isoniazid compared with other standard treatment regimens for latent tuberculosis infection: a decision analysis study.

Background: Latent tuberculosis infection (LTBI) is a critical driver of the global burden of active TB, and therefore LTBI treatment is key for TB elimination. Treatment regimens for LTBI include self-administered daily isoniazid for 6 (6H) or 9 (9H) months, self-administered daily rifampicin plus isoniazid for 3 months (3RH), self-administered daily rifampicin for 4 months (4R) and weekly rifapentine plus isoniazid for 3 months self-administered (3HP-SAT) or administered by a healthcare worker as directly observed therapy (3HP-DOT). Data on the relative cost-effectiveness of these regimens are needed to assist policymakers and clinicians in selecting an LTBI regimen. Objectives: To evaluate the cost-effectiveness of all regimens for treating LTBI. Methods: We developed a Markov model to investigate the cost-effectiveness of 3HP-DOT, 3HP-SAT, 4R, 3RH, 9H and 6H for LTBI treatment in a cohort of 10000 adults with LTBI. Cost-effectiveness was evaluated from a health system perspective over a 20 year time horizon. Results: Compared with no preventive treatment, 3HP-DOT, 3HP-SAT, 4R, 3RH, 9H and 6H prevented 496, 470, 442, 418, 370 and 276 additional cases of active TB per 10000 patients, respectively. All regimens reduced costs and increased QALYs compared with no preventive treatment. 3HP was more cost-effective under DOT than under SAT at a cost of US$27948 per QALY gained. Conclusions: Three months of weekly rifapentine plus isoniazid is more cost-effective than other regimens. Greater recognition of the benefits of short-course regimens can contribute to the scale-up of prevention and achieving the 'End TB' targets.

Cost-effectiveness of Preventive Therapy for Tuberculosis With Isoniazid and Rifapentine Versus Isoniazid Alone in High-Burden Settings.

Background: A short-course regimen of 3 months of weekly rifapentine and isoniazid (3HP) has recently been recommended by the World Health Organization as an alternative to at least 6 months of daily isoniazid (isoniazid preventive therapy [IPT]) for prevention of tuberculosis (TB). The contexts in which 3HP may be cost-effective compared to IPT among people living with human immunodeficiency virus are unknown. Methods: We used a Markov state transition model to estimate the incremental cost-effectiveness of 3HP relative to IPT in high-burden settings, using a cohort of 1000 patients in a Ugandan HIV clinic as an emblematic scenario. Cost-effectiveness was expressed as 2017 US dollars per disability-adjusted life year (DALY) averted from a healthcare perspective over a 20-year time horizon. We explored the conditions under which 3HP would be considered cost-effective relative to IPT. Results: Per 1000 individuals on antiretroviral therapy in the reference scenario, treatment with 3HP rather than IPT was estimated to avert 9 cases of TB and 1 death, costing $9402 per DALY averted relative to IPT. Cost-effectiveness depended strongly on the price of rifapentine, completion of 3HP, and prevalence of latent TB. At a willingness to pay of $1000 per DALY averted, 3HP is likely to be cost-effective relative to IPT only if the price of rifapentine can be greatly reduced (to approximately $20 per course) and high treatment completion (85%) can be achieved. Conclusions: 3HP may be a cost-effective alternative to IPT in high-burden settings, but cost-effectiveness depends on the price of rifapentine, achievable completion rates, and local willingness to pay.

Cost-effectiveness of universal isoniazid preventive therapy among HIV-infected pregnant women in South Africa.

OBJECTIVE: To estimate the incremental cost-effectiveness of universal vs. test-directed treatment of latent tuberculous infection (LTBI) among human immunodeficiency virus (HIV) positive pregnant women in South Africa. METHODS: We compared tuberculin skin test (TST) directed isoniazid preventive therapy (IPT) (TST placement with delivery of IPT to women with positive results) against QuantiFERON®-TB Gold In-Tube (QGIT) directed IPT and universal IPT using decision analysis. Costs were measured empirically in six primary care public health clinics in Matlosana, South Africa. The primary outcome was the incremental cost-effectiveness ratio, expressed in 2016 US$ per disability-adjusted life-year (DALY) averted. RESULTS: We estimated that 29.2 of every 1000 pregnant women would develop TB over the course of 1 year in the absence of IPT. TST-directed IPT reduced this number to 24.5 vs. 22.6 with QGIT-directed IPT and 21.0 with universal IPT. Universal IPT was estimated to cost $640/DALY averted (95% uncertainty range $44-$3146) relative to TST-directed IPT and was less costly and more effective (i.e., dominant) than QGIT-directed IPT. Cost-effectiveness was most sensitive to the probability of developing TB and LTBI prevalence. CONCLUSION: Providing IPT to all eligible women can be a cost-effective strategy to prevent TB among HIV-positive pregnant women in South Africa.

Tuberculosis Prevention in the Private Sector: Using Claims-Based Methods to Identify and Evaluate Latent Tuberculosis Infection Treatment With Isoniazid Among the Commercially Insured.

CONTEXT: Targeted identification and treatment of people with latent tuberculosis infection (LTBI) are key components of the US tuberculosis elimination strategy. Because of recent policy changes, some LTBI treatment may shift from public health departments to the private sector. OBJECTIVES: To (1) develop methodology to estimate initiation and completion of treatment with isoniazid for LTBI using claims data, and (2) estimate treatment completion rates for isoniazid regimens from commercial insurance claims. METHODS: Medical and pharmacy claims data representing insurance-paid services rendered and prescriptions filled between January 2011 and March 2015 were analyzed. PARTICIPANTS: Four million commercially insured individuals 0 to 64 years of age. MAIN OUTCOME MEASURES: Six-month and 9-month treatment completion rates for isoniazid LTBI regimens. RESULTS: There was an annual isoniazid LTBI treatment initiation rate of 12.5/100 000 insured persons. Of 1074 unique courses of treatment with isoniazid for which treatment completion could be assessed, almost half (46.3%; confidence interval, 43.3-49.3) completed 6 or more months of therapy. Of those, approximately half (48.9%; confidence interval, 44.5-53.3) completed 9 months or more. CONCLUSIONS: Claims data can be used to identify and evaluate LTBI treatment with isoniazid occurring in the commercial sector. Completion rates were in the range of those found in public health settings. These findings suggest that the commercial sector may be a valuable adjunct to more traditional venues for tuberculosis prevention. In addition, these newly developed claims-based methods offer a means to gain important insights and open new avenues to monitor, evaluate, and coordinate tuberculosis prevention.

SIRCLE: a randomised controlled cost comparison of self-administered short-course isoniazid and rifapentine for cost-effective latent tuberculosis eradication.

BACKGROUND: Currently, treatment of latent tuberculosis infection (LTBI) in Australia consists most commonly of a 9-month course of isoniazid (9H). A 3-month course of weekly isoniazid and rifapentine (3HP) has been shown to be as effective as 9 months of daily isoniazid, and associated with less hepatotoxicity; however, rifapentine is not currently available in Australia. Introduction of this regimen would have apparent advantages for people with LTBI in Victoria by safely shortening duration of LTBI therapy. However, the cost benefit of this new therapeutic approach is uncertain. AIM: Cost-analysis of standard and short-course therapy for LTBI in an Australian context. METHODS: Single-centre randomised controlled trial conducted between December 2013-March 2016. Participants underwent 1:1 randomisation to either a 9-month course of daily isoniazid or a 12-week course of weekly isoniazid and rifapentine. The primary outcome measure was total healthcare system costs (in Australian dollars; AUD) per completed course of LTBI therapy. Secondary cost analyses were performed to consider varying assumptions regarding commercial cost of rifapentine. RESULTS: Overall, 34 of 40 (85%) participants in the 9H group and 36/40 (90%) in the 3HR group completed therapy. One patient in the 3HP group was hospitalised for a febrile illness; no hospitalisations were recorded in the 9H group. The cost per completed course of 9H was 601 AUD, while that of 3HP was significantly lower at 511 AUD (P < 0.01). CONCLUSIONS: This study provides cost analysis evidence to support the use of 3HP for the treatment of LTBI in Australia.

Cost-Effectiveness of isoniazid preventive therapy among HIV-infected patients clinicaly screened for latent tuberculosis infection in Dar es Salaam, Tanzania: A prospective Cohort study.

BACKGROUND: One of the reasons why Isoniazid preventive therapy (IPT) for Tuberculosis (TB) is not widely used in low income countries is concerns on cost of excluding active TB. We analyzed the cost-effectiveness of IPT provision in Tanzania having ruled out active TB by a symptom-based screening tool. METHODS: Data on IPT cost-effectiveness was prospectively collected from an observational cohort study of 1283 HIV-infected patients on IPT and 1281 controls; followed up for 24 months. The time horizon for the analysis was 2 years. Number of TB cases prevented and deaths averted were used for effectiveness. A micro costing approach was used from a provider perspective. Cost was estimated on the basis of clinical records, market price or interviews with medical staff. We annualized the cost at a discount of 3%. A univariate sensitivity analysis was done. Results are presented in US$ at an average annual exchange rate for the year 2012 which was Tanzania shillings 1562.4 for 1 US $. RESULTS: The number of TB cases prevented was 420/100,000 persons receiving IPT. The number of deaths averted was 979/100,000 persons receiving IPT. Incremental cost due to IPT provision was US$ 170,490. The incremental cost effective ratio was US $ 405.93 per TB case prevented and US $ 174.15 per death averted. These costs were less than 3 times the 768 US $ Gross Domestic Product (GDP) per capita for Tanzania in the year 2014, making IPT provision after ruling out active TB by the symptom-based screening tool cost-effective. The results were robust to changes in laboratory and radiological tests but not to changes in recurrent, personnel, medication and utility costs. CONCLUSION: IPT should be given to HIV-infected patients who screen negative to symptom-based TB screening questionnaire. Its cost-effectiveness supports government policy to integrate IPT to HIV/AIDS care and treatment in the country, given the availability of budget and the capacity of health facilities.

Impacts of 12-dose regimen for latent tuberculosis infection: Treatment completion rate and cost-effectiveness in Taiwan.

Treatment of latent tuberculosis infection (LTBI) is essential for eradicating tuberculosis (TB). Moreover, the patient adherence is crucial in determining the effectiveness of TB control. Isoniazid given by DOTS daily for 9 months (9H) is the standard treatment for LTBI in Taiwan. However, the completion rate is low due to the long treatment period and its side effects. The combined regimen using a high dose of rifapentine/isoniazid once weekly for 12 weeks (3HP) has been used as an alternative treatment option for LTBI in the United States. This may result in a higher completion rate. In this pilot study, patient adherence and cost of these 2 treatment regimens were investigated. Thus, we aimed to assess the treatment completion rate and costs of 3HP and compare to those with 9H.Data from 691 cases of LTBI treatments including 590 cases using the conventional regimen and 101 cases with rifapentine/Isoniazid were collected. The cost was the sum of the cost of treatment with Isoniazid for 9 months or with rifapentin/Isoniazid for 3 months of all contacts. The effectiveness was the cost of cases of tuberculosis avoided.In this study, the treatment completion rate for patients prescribed with the 3 months rifapentine/isoniazid regimen (97.03%) was higher than those given the conventional 9-month isoniazid regimen (87.29%) (P <0.001). The cost of 3HP and 9H was US$261.24 and US$717.3, respectively. The cost-effectiveness ratio with isoniazid for 9 months was US$ 15392/avoided 1 case of tuberculosis and US$ 5225/avoided 1 case of tuberculosis with 3HP. In addition, when compared with the conventional regimen, there were fewer patients discontinued with rifapentine/isoniazid regimen due to undesirable side effects.This was the first study to compare the 2 treatment regimens in Taiwan, and it showed that a short-term high-dosage rifapentine/isoniazid treatment regimen reduced costs and resulted in higher treatment completion than the standard LTBI isoniazid treatment.

Cost-effectiveness of isoniazid preventive therapy for HIV-infected pregnant women in India.

BACKGROUND: India has a high burden of active tuberculosis (TB) and human immunodeficiency virus (HIV) infection. Pregnancy increases the risks of developing TB in HIV-infected women. Isoniazid preventive therapy (IPT) reduces progression to TB, but may increase costs and hepatotoxicity. The cost-effectiveness of IPT for HIV-infected pregnant women in India is unknown. DESIGN: We evaluated the cost-effectiveness of antepartum IPT among HIV-infected women in India using a decision-analytic model. We compared current practice (no IPT) with: Intervention 1 (IPT regardless of CD4 count) and Intervention 2 (IPT for those with CD4 count â©¿ 200 cells/µl). We modeled IPT irrespective of tuberculin skin test (TST) status and TST-driven strategies. Primary outcomes were anticipated costs, disability-adjusted life-years (DALYs) and TB cases. RESULTS: Both IPT interventions are highly cost-effective compared to no IPT at current willingness-to-pay thresholds (respectively US$178.00 and US$201.00 per DALY averted for Interventions 1 and 2). However, providing IPT irrespective of CD4 count results in the greatest health benefits (21 TB cases averted/1000 patients) compared to current practice. IPT irrespective of TST status was also highly cost-effective compared to TST-driven IPT (respectively US$1027.00 and US$1154.00/DALY averted for Interventions 1 and 2). CONCLUSION: Antepartum IPT for HIV-infected women is highly cost-effective for TB prevention compared to current practices in India.

Implementation and Operational Research: Cost-Effectiveness of Antiretroviral Therapy and Isoniazid Prophylaxis to Reduce Tuberculosis and Death in People Living With HIV in Botswana.

OBJECTIVE: In Botswana, a 36-month course of isoniazid treatment of latent tuberculosis (TB) infection [isoniazid preventive therapy (IPT)] was superior to 6-month IPT in reducing TB and death in persons living with HIV (PLHIV), having positive tuberculin skin tests (TSTs) but not in those with negative TST. We examined the cost-effectiveness of IPT in Botswana, where antiretroviral therapy (ART) is widely available. DESIGN: Using a decision-analytic model, we determined the incremental cost-effectiveness of strategies for reducing TB and death in 10,000 PLHIV over 36 months. METHODS: IPT for 6 months and provision of ART if CD4 lymphocyte count <250 cells per microliter (2011 Botswana policy) was compared with 6 alternative strategies that varied the use of IPT, TST, and ART for CD4 count thresholds, including CD4 <350 and <500 cells per microliter. RESULTS: Botswana policy, 2011 was dominated by most other strategies. IPT of 36 months for TST-positive PLHIV with ART for CD4 <250 cells per microliter resulted in 120 fewer TB cases for an additional cost of $1612 per case averted and resulted in 80 fewer deaths for an additional $2418 per death averted compared with provision of 6-month IPT to TST-positive PLHIV who received ART for CD4 <250 cells per microliter, the next most effective strategy. Alternative strategies offered lower incremental effectiveness at higher cost. These findings remained consistent in sensitivity analyses. CONCLUSIONS: A strategy of treating PLHIV who have positive TST with 36-month IPT is more cost effective for reducing both TB and death compared with providing IPT without a TST, providing only 6-month IPT, or expanding ART eligibility without IPT.

Cost-effectiveness of tuberculosis screening and isoniazid treatment in the TB/HIV in Rio (THRio) Study.

OBJECTIVE: To estimate the incremental cost-effectiveness of tuberculosis (TB) screening and isoniazid preventive therapy (IPT) among human immunodeficiency virus (HIV) infected adults in Rio de Janeiro, Brazil. DESIGN: We used decision analysis, populated by data from a cluster-randomized trial, to project the costs (in 2010 USD) and effectiveness (in disability-adjusted life years [DALYs] averted) of training health care workers to implement the tuberculin skin test (TST), followed by IPT for TST-positive patients with no evidence of active TB. This intervention was compared to a baseline of usual care. We used time horizons of 1 year for the intervention and 20 years for disease outcomes, with all future DALYs and medical costs discounted at 3% per year. RESULTS: Providing this intervention to 100 people would avert 1.14 discounted DALYs (1.57 undiscounted DALYs). The median estimated incremental cost-effectiveness ratio was $2273 (IQR $1779-$3135) per DALY averted, less than Brazil's 2010 per capita gross domestic product (GDP) of $11,700. Results were most sensitive to the cost of providing the training. CONCLUSION: Training health care workers to screen HIV-infected adults with TST and provide IPT to those with latent tuberculous infection can be considered cost-effective relative to the Brazilian GDP per capita.

Prevalence of extended treatment in pulmonary tuberculosis patients receiving first-line therapy and its association with recurrent tuberculosis in Beijing, China.

BACKGROUND: In China, it is known that extended treatment is given to patients with pulmonary TB after they have successfully completed 6 months of first-line treatment. This practice is not officially reported to the National Tuberculosis Control Programme, so there are no data on its prevalence, its possible benefits in terms of preventing recurrent disease or the costs. This study aimed to provide information, from a single TB dispensary in Beijing, China, on the prevalence of extended anti-TB treatment and its relationship with recurrent TB. METHODS: Retrospective cohort study using the electronic national TB information system and dispensary medical records. RESULTS: Of 935 patients with pulmonary TB who completed 6-7 months of first-line drug treatment, 399 (43%) were given extended treatment. This was more common in patients with smear-positive disease, and those with lung cavities and more extensive radiographic lobar involvement at the time of diagnosis. Over 3-4 years' follow-up, recurrent disease was not significantly different in patients who received extended treatment (2.8%, 11/399) as compared to those who received the standard 6-month treatment (3.7%, 20/534). The median length of extended treatment was 89 days at a median cost of US$111 for drugs and US$32 for laboratory examinations. CONCLUSIONS: This study shows that extended treatment is common in one TB dispensary in Beijing. Further studies are needed to determine the countrywide prevalence of this practice and ascertain more conclusively the apparent lack of benefit.

Current treatment options for latent tuberculosis infection.

Treatment of latent tuberculosis infection (LTBI) is a key component in TB control strategies worldwide. However, as people with LTBI are neither symptomatic nor contagious, any screening decision should be weighed carefully against the potential benefit of preventing active disease in those who are known to be at higher risk and are willing to accept therapy for LTBI. This means that a targeted approach is desirable to maximize cost effectiveness and to guarantee patient adherence. We focus on LTBI treatment strategies in patient populations at increased risk of developing active TB, including candidates for treatment with tumor necrosis factor-α blockers. In the last 40 years, isoniazid (INH) has represented the keystone of LTBI therapy across the world. Although INH remains the first therapeutic option, alternative treatments that are effective and associated with increased adherence and economic savings are available. Current recommendations, toxicity, compliance, and cost issues are discussed in detail in this review. A balanced relationship between the patient and healthcare provider could increase adherence, while cost-saving treatment strategies with higher effectiveness, fewer side effects, and of shorter duration should be offered as preferred.

Management of children exposed to Mycobacterium tuberculosis: a public health evaluation in West Java, Indonesia.

OBJECTIVE: To investigate qualitatively and quantitatively the performance of a programme for managing the child contacts of adult tuberculosis patients in Indonesia. METHODS: A public health evaluation framework was used to assess gaps in a child contact management programme at a lung clinic. Targets for programme performance indicators were derived from established programme indicator targets, the scientific literature and expert opinion. Compliance with tuberculosis screening, the initiation of isoniazid preventive therapy in children younger than 5 years, the accuracy of tuberculosis diagnosis and adherence to preventive therapy were assessed in 755 child contacts in two cohorts. In addition, 22 primary caregivers and 34 clinic staff were interviewed to evaluate knowledge and acceptance of child contact management. The cost to caregivers was recorded. Gaps between observed and target indicator values were quantified. FINDINGS: THE GAPS BETWEEN OBSERVED AND TARGET PERFORMANCE INDICATORS WERE: 82% for screening compliance; 64 to 100% for diagnostic accuracy, 50% for the initiation of preventive therapy, 54% for adherence to therapy and 50% for costs. Many staff did not have adequate knowledge of, or an appropriate attitude towards, child contact management, especially regarding isoniazid preventive therapy. Caregivers had good knowledge of screening but not of preventive therapy and had difficulty travelling to the clinic and paying costs. CONCLUSION: The study identified widespread gaps in the performance of a child contact management system in Indonesia, all of which appear amenable to intervention. The public health evaluation framework used could be applied in other settings where child contact management is failing.