Cost-Effectiveness of Vonoprazan-Based and Rifabutin-Based vs Other Regimens as First-Line Treatment of Helicobacter pylori Infection in the United States.

INTRODUCTION: The economic and clinical implications of eradicating Helicobacter pylori ( H. pylori ) with vonoprazan-based and rifabutin-based regimens vs other existing prepackaged first-line treatment options in the United States are unknown. Therefore, we evaluated the cost-effectiveness of vonoprazan-based and rifabutin-based and other prepackaged regimens for the first-line treatment of H. pylori from the perspective of US healthcare payers. METHODS: We used the state-transition Markov model to conduct a cost-effectiveness analysis of H. pylori eradication with clarithromycin triple, bismuth quadruple, vonoprazan dual, vonoprazan triple, and rifabutin triple regimens. In a cycle length of 2 months, the model estimated the expected costs (expressed in 2022 US$), expected quality-adjusted life-years (QALY), incremental cost-effectiveness ratios, and expected net monetary benefit over 20 years. In addition, we accounted for the present value of future costs and QALY by applying a 3% discounting rate. RESULTS: In this study, rifabutin triple therapy had a lower expected cost but was more effective than clarithromycin triple, bismuth quadruple, and vonoprazan dual regimens; hence, it dominated them. Vonoprazan triple therapy had a higher expected cost (US$ 1,172 vs US$ 1,048) and expected QALY (14.262 vs 14.256) than rifabutin triple therapy, yielding an estimated incremental cost-effectiveness ratio of US$ 22,573/QALY. The study suggested that vonoprazan triple treatment had the highest expected net monetary benefit and was the most cost-effective at willingness-to-pay thresholds between US$50,000 and US$150,000 per QALY, followed by rifabutin triple therapy. DISCUSSION: H. pylori infection eradication with vonoprazan triple therapy would provide the greatest net health and monetary benefit from the perspective of US healthcare payers.

Protease inhibitor-containing antiretroviral treatment and tuberculosis: can rifabutin fill the breach?

OBJECTIVE: To assess how to best manage co-administration of rifabutin (RFB) and human immunodeficiency virus 1 (HIV-1) protease inhibitor (PI) containing antiretroviral treatment (ART). Recommended for initial anti-tuberculosis treatment, rifampicin (RMP) lowers PI concentrations below therapeutic levels, posing significant challenges for ART. As RFB has little effect on PI concentrations, it could be an alternative to RMP. METHODS: A review of the scientific literature on the safety and efficacy of RFB for adult tuberculosis (TB) treatment was conducted, focusing on ART-TB co-therapy. A cost comparison was performed between treatment regimens, and estimates of the burden of TB disease in patients on ART were used to model RFB demand in low- and middle-income countries (LMICs). RESULTS: Eleven clinical studies were identified, comprising 1543 TB patients treated with RFB; 980 (64%) were living with HIV. RFB was as safe and effective as RMP, including in 313 patients receiving co-administered ART (unboosted PIs included indinavir, nelfinavir or saquinavir; a minority received ritonavir [RTV] boosted amprenavir or saquinavir). The total cost for 6 months of all HIV and TB treatment containing RTV-boosted lopinavir (LPV) and RFB is US$410, compared to US$455 if RMP is used with LPV super-boosted with RTV. Our model suggests that demand for RFB in LMICs could be between 10,000 and 18,000 courses by 2012. CONCLUSION: RFB is effective and safe in combination with the PIs studied, cost-saving for co-therapy with currently recommended boosted PIs, and may have a pivotal role in the roll-out of ART. Further research into a daily dose of RFB to simplify dosing regimens and developing fixed-dose combinations can enhance the public sector roll-out of ART.

Model for simulation of HIV/AIDS and cost-effectiveness of preventing non-tuberculous mycobacterial (MAC)-disease.

Because most HIV-infected patients die of diseases caused by opportunistic pathogens, the prevention of these infections is an important clinical issue. Cost-containment in the healthcare system is a subject of high priority in public debate. Methods to determine cost-effectiveness of different therapeutic strategies are therefore needed to obtain valid data as the basis for decisions on cost reduction without a decrease in the quality of care. A disease state transition model based on a Markov process was developed to simulate the natural history of HIV infection and the acquired immunodeficiency syndrome (AIDS). Using this model survival time and treatment costs for every patient can be estimated and the results of alternative medications compared. We determined the cost-effectiveness (per life-year saved, LYS) of different strategies for prevention of Mycobacterium avium complex infections in AIDS patients whose treatment regimens include protease inhibitors. The cost-effectiveness ratios for treatment strategies vary from 13,510 euro to 46,152 euro per LYS without protease inhibitors and from 22,309 euro to 51,336 euro with protease inhibitors. When azithromycin, clarithromycin, and rifabutin were compared, azithromycin was the most cost-effective medication for preventing M. avium complex. The results were stable against a wide range of parameter variations concerning costs and incidence rates.

The cost-effectiveness of prophylaxis for Mycobacterium avium complex in AIDS.

OBJECTIVE: To develop a simulation model to project costs, life expectancy, and cost-effectiveness in discounted dollars per quality-adjusted life-year (QALY) saved for clinical strategies to prevent Mycobacterium avium complex (MAC) in patients with AIDS. METHODS: We used natural history data from the Multicenter AIDS Cohort Study, efficacy and toxicity data from randomized clinical trials, and cost data from the AIDS Cost and Services Utilization Survey. The model permits timing of prophylaxis to be stratified by CD4 count (201-300, 101-200, 51-100, and < or = 50/mm3), and allows combinations of prophylaxis, crossover to second- and third-line agents for toxicity, and consideration of adherence, resistance, and quality of life. RESULTS: The model projects that the average HIV-infected patient with a beginning CD4 count between 201 and 300/mm3 has total lifetime costs of approximately $43,150 and a quality-adjusted life expectancy of 42.35 months. If azithromycin prophylaxis for M. avium complex is begun after the CD4 declines to 50/mm3, costs and quality-adjusted survival increase to approximately $44,040 and 42.78 months, respectively, for an incremental cost-effectiveness ratio of $25,000/QALY compared with no M. avium complex prophylaxis. Other prophylaxis options (i.e., rifabutin, clarithromycin, and combination therapies) either cost more but offer shorter survival, or have cost-effectiveness ratios above $260,000/QALY. Sensitivity analysis reveals that, for reasonable assumptions about quality of life, risk of infection, prophylaxis cost, adherence, and resistance, azithromycin remains the most cost-effective prophylaxis option. CONCLUSIONS: Azithromycin prophylaxis, begun after the CD4 count has declined to 50/mm3, is the most cost-effective M. avium complex prophylaxis strategy. Consistent with new United States Public Health Service guidelines, it should be the first-line prophylaxis option.

[Manifestations, diagnosis and treatment of non-tuberculous mycobacterial infections in patients with HIV infection]. / Manifestations, diagnostic et traitement des infections mycobactériennes non tuberculeuses chez les patients porteurs du VIH.

The most frequent bacterial infections in patients infected with HIV and suffering from AIDS are non-tuberculous mycobacterial infections. Their incidence is increasing all the more as the survival of profoundly immunocompromised patients is prolonged. There are unknown factors as regards the precise origin of these infections and as to the exact epidemiology of atypical mycobacteria. It is known that 95 per cent of atypical mycobacterial infections are due to M. avium. If the pathophysiology of the infection (involving the intervention of cytokines and also factors in relation to the virulence of the germ) is imperfectly understood, the atypical mycobacteria are an independent cause of mortality in advanced stages of the disease. The clinical picture is that of a low grade fever with weight loss and a deterioration in the general physical state. There are subtle physical signs such as a fall in the functional capacity accompanied by weight loss and an unexplained anaemia these should also suggest a diagnosis. More rarely the infection will be localised. The clinical diagnosis will be confirmed by bacteriology which has been aided by recent progress in molecular biology. With the arrival of the newer macrolides it has been shown that treatment prolongs survival in a significant manner. Current recommendations consist of a treatment with a combined regime including a minimum of Clarithyromycin and Ethambutol. The place for polychemotherapy remains to be determined in particular the role for Rifabutine and Amikacine. Immunomodulation by interferon-gamma or GCSF are also under review. The duration of treatment and the necessity of long term suppressive treatment is the object of randomised studies. Prophylaxis is currently recommended for patients with CD4 < 75/mm3. The role of Rifabutine and the new macrolides remains to be determined. Finally, in a large European study the objective is to compare prophylaxis to systematic bacteriological surveillance both as regards efficacy, tolerance, and in terms of pharmaco-economics.

Rifabutin: a review with emphasis on its role in the prevention of disseminated Mycobacterium avium complex infection.

OBJECTIVE: To discuss the mechanism of action, in vitro and in vivo activity, pharmacokinetics, clinical trials, adverse effects, drug interactions, and dosage guidelines of rifabutin. DATA SOURCES: Pertinent literature published between 1982 and 1993 was identified via a MEDLINE search. Published proceedings of selected conferences were also reviewed. STUDY SELECTION: Selected basic science, microbiologic, and pharmacokinetic articles were evaluated. Because only limited data regarding rifabutin were available in the literature, all clinical trials involving the use of rifabutin in the prevention of Mycobacterium avium complex (MAC) infection in AIDS patients were reviewed. DATA SYNTHESIS: Rifabutin is a rifamycin derivative that was approved recently for the prevention of disseminated MAC disease in patients with advanced HIV infection. The drug has in vitro and in vivo activity against gram-positive bacteria, gram-negative bacteria, and mycobacteria. Two prospective, randomized, double-blind, placebo-controlled, multicenter trials demonstrated that rifabutin decreased the progression to MAC bacteremia in AIDS patients by about 50 percent. Adverse effects that resulted in the discontinuation of rifabutin prophylaxis occurred in 16 percent of patients. Rifabutin induces hepatic enzymes to a lesser extent than does rifampin, but dosage adjustment of drugs that are known to interact with rifampin may be required. CONCLUSIONS: Rifabutin is the only drug shown to be effective in the prevention of MAC bacteremia in AIDS patients; therefore, it should be made available as a formulary agent. It may be reasonable to delay initiation of rifabutin prophylaxis until CD4 lymphocyte counts are less than 75-50/mm3.

The early bactericidal activity of rifabutin in patients with pulmonary tuberculosis measured by sputum viable counts: a new method of drug assessment.

The activity of rifabutin and rifampicin against rapidly growing, extra-cellular Mycobacterium tuberculosis in cavity walls was measured by counting colony-forming units (cfu) in the sputum of 74 patients with newly diagnosed, severe pulmonary tuberculosis during the first 2 days of daily chemotherapy. The fall in counts, (log10 cfu/mL sputum/day), was termed the early bactericidal activity (EBA). The EBA, a highly reproducible measure within groups of 10-13 patients, was -0.015 for a low EBA reference group (who received no chemotherapy) and 0.495 for a high EBA reference group (who received 300 mg isoniazid daily). The EBAs in patients receiving 300 and 600 mg rifabutin were 0.014 and 0.075, and for those taking 150, 300 and 600 mg rifampicin 0.021, 0.150 and 0.204, respectively. Weight-for-weight, the ratio rifabutin to rifampicin producing the same EBA was estimated to be 2.73 (95% confidence limits 1.96-3.78). Determination of the EBA is a rapid and economical method of comparing the potency in human lesions of drugs of the same type before embarking on a conventional clinical trial.